@article{rose_bentley_maity_maguire_planchart_spasojevic_liu_thorp jr_hoyo_2024, title={Association between F2-isoprostanes and self-reported stressors in pregnant americans of African and European ancestry}, volume={10}, ISSN={["2405-8440"]}, DOI={10.1016/j.heliyon.2024.e25578}, abstractNote={BackgroundPoor birth outcomes such as preterm birth/delivery disproportionately affect African Americans compared to White individuals. Reasons for this disparity are likely multifactorial, and include prenatal psychosocial stressors, and attendant increased lipid peroxidation; however, empirical data linking psychosocial stressors during pregnancy to oxidative status are limited.MethodsWe used established scales to measure five psychosocial stressors. Maternal adverse childhood experiences, financial stress, social support, anxiety, and depression were measured among 50 African American and White pregnant women enrolled in the Stress and Health in Pregnancy cohort. Liquid chromatography‐tandem mass spectrometry was used to measure biomarkers of oxidative stress (four urinary F2-isoprostane isomers), to estimate oxidative status. Linear regression models were used to evaluate associations between psychosocial stressors, prenatal oxidative status and preterm birth.ResultsAfter adjusting for maternal obesity, gestational diabetes, and cigarette smoking, African American women with higher oxidative status were more likely to report higher maternal adverse childhood experience scores (β = 0.16, se = 1.07, p-value = 0.024) and depression scores (β = 0.05, se = 0.02, p = 0.014). Higher oxidative status was also associated with lower gestational age at birth (β = −0.13, se = 0.06, p = 0.04) in this population. These associations were not apparent in Whites. However, none of the cross-product terms for race/ethnicity and social stressors reached statistical significance (p > 0.05).ConclusionWhile the small sample size limits inference, our novel data suggest that psychosocial stressors may contribute significantly to oxidative stress during pregnancy, and preterm birth or delivery African Americans. If replicated in larger studies, these findings would support oxidative stress reduction using established dietary or pharmacological approaches present a potential avenue to mitigate adverse effects of psychosocial stressors on birth outcomes.}, number={3}, journal={HELIYON}, author={Rose, Deborah K. and Bentley, Loren and Maity, Arnab and Maguire, Rachel L. and Planchart, Antonio and Spasojevic, Ivan and Liu, Andy J. and Thorp Jr, John and Hoyo, Cathrine}, year={2024}, month={Feb} } @article{monangi_xu_fan_khanam_khan_deb_pervin_price_kaur_al mahmud_et al._2024, title={Association of maternal prenatal copper concentration with gestational duration and preterm birth: a multicountry meta-analysis}, volume={119}, ISSN={["1938-3207"]}, DOI={10.1016/j.ajcnut.2023.10.011}, abstractNote={Copper (Cu), an essential trace mineral regulating multiple actions of inflammation and oxidative stress, has been implicated in risk for preterm birth (PTB). Determine the association of maternal Cu concentration during pregnancy with PTB risk and gestational duration in a large multi-cohort study including diverse populations. Maternal plasma or serum samples of 10,449 singleton live births were obtained from 18 geographically diverse study cohorts. Maternal Cu concentrations were determined using inductively coupled plasma mass spectrometry (ICP-MS). The associations of maternal Cu with PTB and gestational duration were analyzed using logistic and linear regressions for each cohort. The estimates were then combined using meta-analysis. Associations between maternal Cu and acute phase reactants (APRs), infection status were analyzed in 1239 samples from the Malawi cohort. The maternal prenatal Cu concentration in our study samples followed normal distribution with mean of 1.92 μg/ml and standard deviation of 0.43 μg/ml, and Cu concentrations increased with gestational age up to 20 weeks. The random effect meta-analysis across 18 cohorts revealed that 1 μg/ml increase in maternal Cu concentration was associated with higher risk of PTB with OR of 1.30 (95% CI: 1.08 to 1.57) and shorter gestational duration of 1.64 days (95% CI: 0.56 to 2.73). In the Malawi cohort, higher maternal Cu concentration, concentrations of multiple APRs and infections (malaria and HIV) were correlated and associated with greater risk of PTB and shorter gestational duration. Our study supports robust negative association between maternal Cu and gestational duration and positive association with risk for preterm birth. Cu concentration was strongly correlated with APRs and infection status suggesting its potential role in inflammation, a pathway implicated in the mechanisms of PTB. Therefore, maternal Cu could be used as potential marker of integrated inflammatory pathways during pregnancy and risk for preterm birth.}, number={1}, journal={AMERICAN JOURNAL OF CLINICAL NUTRITION}, author={Monangi, Nagendra K. and Xu, Huan and Fan, Yue-Mei and Khanam, Rasheeda and Khan, Waqasuddin and Deb, Saikat and Pervin, Jesmin and Price, Joan T. and Kaur, Lovejeet and Al Mahmud, Abdullah and et al.}, year={2024}, month={Jan}, pages={221–231} } @article{vidal_sosnowski_marchesoni_grenier_thorp_murphy_johnson_schlief_hoyo_2024, title={Maternal adverse childhood experiences (ACEs) and offspring imprinted gene DMR methylation at birth}, volume={19}, ISSN={["1559-2308"]}, DOI={10.1080/15592294.2023.2293412}, abstractNote={ABSTRACT Adverse childhood experiences (ACEs) contribute to numerous negative health outcomes across the life course and across generations. Here, we extend prior work by examining the association of maternal ACEs, and their interaction with financial stress and discrimination, with methylation status within eight differentially methylated regions (DMRs) in imprinted domains in newborns. ACEs, financial stress during pregnancy, and experience of discrimination were self-reported among 232 pregnant women. DNA methylation was assessed at PEG10/SGCE, NNAT, IGF2, H19, PLAGL1, PEG3, MEG3-IG, and DLK1/MEG3 regulatory sequences using pyrosequencing. Using multivariable linear regression models, we found evidence to suggest that financial stress was associated with hypermethylation of MEG3-IG in non-Hispanic White newborns; discrimination was associated with hypermethylation of IGF2 and NNAT in Hispanic newborns, and with hypomethylation of PEG3 in non-Hispanic Black newborns. We also found evidence that maternal ACEs interacted with discrimination to predict offspring PLAGL1 altered DMR methylation, in addition to interactions between maternal ACEs score and discrimination predicting H19 and SGCE/PEG10 altered methylation in non-Hispanic White newborns. However, these interactions were not statistically significant after multiple testing corrections. Findings from this study suggest that maternal ACEs, discrimination, and financial stress are associated with newborn aberrant methylation in imprinted gene regions.}, number={1}, journal={EPIGENETICS}, author={Vidal, Adriana C. and Sosnowski, David W. and Marchesoni, Joddy and Grenier, Carole and Thorp, John and Murphy, Susan K. and Johnson, Sara B. and Schlief, Billy and Hoyo, Cathrine}, year={2024}, month={Dec} } @article{sosnowski_rojo-wissar_peng_parade_sharkey_hoyo_murphy_hernandez_johnson_2024, title={Maternal childhood adversity and infant epigenetic aging: Moderation by restless sleep during pregnancy}, volume={66}, ISSN={["1098-2302"]}, DOI={10.1002/dev.22464}, abstractNote={Abstract}, number={2}, journal={DEVELOPMENTAL PSYCHOBIOLOGY}, author={Sosnowski, David W. and Rojo-Wissar, Darlynn M. and Peng, Gang and Parade, Stephanie H. and Sharkey, Katherine and Hoyo, Cathrine and Murphy, Susan K. and Hernandez, Raquel G. and Johnson, Sara B.}, year={2024}, month={Feb} } @article{vidal_chandramouli_marchesoni_brown_liu_murphy_maguire_wang_abdelmalek_mavis_et al._2023, title={AHRR Hypomethylation mediates the association between maternal smoking and metabolic profiles in children}, volume={7}, ISSN={["2471-254X"]}, DOI={10.1097/HC9.0000000000000243}, abstractNote={ Background: Tobacco smoking during pregnancy is associated with metabolic dysfunction in children, but mechanistic insights remain limited. Hypomethylation of cg05575921 in the aryl hydrocarbon receptor repressor (AHRR) gene is associated with in utero tobacco smoke exposure. In this study, we evaluated whether AHRR hypomethylation mediates the association between maternal smoking and metabolic dysfunction in children. }, number={10}, journal={HEPATOLOGY COMMUNICATIONS}, author={Vidal, Adriana C. and Chandramouli, Shivram A. and Marchesoni, Joddy and Brown, Nia and Liu, Yukun and Murphy, Susan K. and Maguire, Rachel and Wang, Yaxu and Abdelmalek, Manal F. and Mavis, Alisha M. and et al.}, year={2023}, month={Oct} } @article{harris_friedman_starling_dabelea_johnson_fuemmeler_jima_murphy_hoyo_jansen_et al._2023, title={An epigenome-wide association study of child appetitive traits and DNA methylation}, volume={191}, ISSN={["1095-8304"]}, DOI={10.1016/j.appet.2023.107086}, abstractNote={The etiology of childhood appetitive traits is poorly understood. Early-life epigenetic processes may be involved in the developmental programming of appetite regulation in childhood. One such process is DNA methylation (DNAm), whereby a methyl group is added to a specific part of DNA, where a cytosine base is next to a guanine base, a CpG site. We meta-analyzed epigenome-wide association studies (EWASs) of cord blood DNAm and early-childhood appetitive traits. Data were from two independent cohorts: the Generation R Study (n = 1,086, Rotterdam, the Netherlands) and the Healthy Start study (n = 236, Colorado, USA). DNAm at autosomal methylation sites in cord blood was measured using the Illumina Infinium HumanMethylation450 BeadChip. Parents reported on their child's food responsiveness, emotional undereating, satiety responsiveness and food fussiness using the Children's Eating Behaviour Questionnaire at age 4-5 years. Multiple regression models were used to examine the association of DNAm (predictor) at the individual site- and regional-level (using DMRff) with each appetitive trait (outcome), adjusting for covariates. Bonferroni-correction was applied to adjust for multiple testing. There were no associations of DNAm and any appetitive trait when examining individual CpG-sites. However, when examining multiple CpGs jointly in so-called differentially methylated regions, we identified 45 associations of DNAm with food responsiveness, 7 associations of DNAm with emotional undereating, 13 associations of DNAm with satiety responsiveness, and 9 associations of DNAm with food fussiness. This study shows that DNAm in the newborn may partially explain variation in appetitive traits expressed in early childhood and provides preliminary support for early programming of child appetitive traits through DNAm. Investigating differential DNAm associated with appetitive traits could be an important first step in identifying biological pathways underlying the development of these behaviors.}, journal={APPETITE}, author={Harris, Holly A. and Friedman, Chloe and Starling, Anne P. and Dabelea, Dana and Johnson, Susan L. and Fuemmeler, Bernard F. and Jima, Dereje and Murphy, Susan K. and Hoyo, Cathrine and Jansen, Pauline W. and et al.}, year={2023}, month={Dec} } @article{kadalayil_alam_white_ghantous_walton_gruzieva_merid_kumar_roy_solomon_et al._2023, title={Analysis of DNA methylation at birth and in childhood reveals changes associated with season of birth and latitude}, volume={15}, ISSN={["1868-7083"]}, DOI={10.1186/s13148-023-01542-5}, abstractNote={Abstract}, number={1}, journal={CLINICAL EPIGENETICS}, author={Kadalayil, Latha and Alam, Md. Zahangir and White, Cory Haley and Ghantous, Akram and Walton, Esther and Gruzieva, Olena and Merid, Simon Kebede and Kumar, Ashish and Roy, Ritu P. and Solomon, Olivia and et al.}, year={2023}, month={Sep} } @article{tilves_zhao_differding_zhang_liu_hoyo_ostbye_benjamin-neelon_mueller_2023, title={Associations of Plastic Bottle Exposure with Infant Growth, Fecal Microbiota, and Short-Chain Fatty Acids}, volume={11}, ISSN={["2076-2607"]}, DOI={10.3390/microorganisms11122924}, abstractNote={Background/Objectives: Murine models show that plastics, via their chemical constituents (e.g., phthalates), influence microbiota, metabolism, and growth. However, research on plastics in humans is lacking. Here, we examine how the frequency of plastic bottle exposure is associated with fecal microbiota, short-chain fatty acids (SCFAs), and anthropometry in the first year of life. Subjects/Methods: In 442 infants from the prospective Nurture birth cohort, we examined the association of frequency of plastic bottle feeding at 3 months with anthropometric outcomes (skinfolds, length-for-age, and weight-for-length) at 12 months of age and growth trajectories between 3 and 12 months. Furthermore, in a subset of infants (n = 70) that contributed fecal samples at 3 months and 12 months of age, we examined plastic bottle frequency in relation to fecal microbiota composition and diversity (measured by 16S rRNA gene sequencing of V4 region), and fecal SCFA concentrations (quantified using gas chromatography mass spectrometry). Results: At 3 months, 67.6% of infants were plastic bottle fed at every feeding, 15.4% were exclusively breast milk fed, and 48.9% were exclusively formula fed. After adjustment for potential confounders, infants who were plastic bottle fed less than every feeding compared to those who were plastic bottle fed at every feeding at 3 months did not show differences in anthropometry over the first 12 months of life, save for lower length-for-age z-score at 12 months (adjusted β = −0.45, 95% CI: −0.76, −0.13). Infants who were plastic bottle fed less than every feeding versus every feeding had lower fecal microbiota alpha diversity at 3 months (mean difference for Shannon index: −0.59, 95% CI: −0.99, −0.20) and lower isovaleric acid concentration at 3 months (mean difference: −2.12 μmol/g, 95% CI: −3.64, −0.60), but these results were attenuated following adjustment for infant diet. Plastic bottle frequency was not strongly associated with microbiota diversity or SCFAs at 12 months after multivariable adjustment. Frequency of plastic bottle use was associated with differential abundance of some bacterial taxa, however, significance was not consistent between statistical approaches. Conclusions: Plastic bottle frequency at 3 months was not strongly associated with measures of adiposity or growth (save for length-for-age) over the first year of life, and while plastic bottle use was associated with some features of fecal microbiota and SCFAs in the first year, these findings were attenuated in multivariable models with infant diet. Future research is needed to assess health effects of exposure to other plastic-based products and objective measures of microplastics and plastic constituents like phthalates.}, number={12}, journal={MICROORGANISMS}, author={Tilves, Curtis and Zhao, Heather Jianbo and Differding, Moira K. and Zhang, Mingyu and Liu, Tiange and Hoyo, Cathrine and Ostbye, Truls and Benjamin-Neelon, Sara E. and Mueller, Noel T.}, year={2023}, month={Dec} } @article{zaltz_mueller_hoyo_ostbye_benjamin-neelon_2023, title={Breastfeeding and less healthy beverage intake during the first year of life}, ISSN={["2047-6302"]}, DOI={10.1111/ijpo.13086}, abstractNote={Abstract}, journal={PEDIATRIC OBESITY}, author={Zaltz, Daniel A. and Mueller, Noel T. and Hoyo, Cathrine and Ostbye, Truls and Benjamin-Neelon, Sara E.}, year={2023}, month={Nov} } @article{wang_tzeng_huang_maguire_hoyo_allen_2023, title={Duration of exposure to epidural anesthesia at delivery, DNA methylation in umbilical cord blood and their association with offspring asthma in Non-Hispanic Black women}, volume={9}, ISSN={["2058-5888"]}, DOI={10.1093/eep/dvac026}, abstractNote={Abstract}, number={1}, journal={ENVIRONMENTAL EPIGENETICS}, author={Wang, Yaxu and Tzeng, Jung-Ying and Huang, Yueyang and Maguire, Rachel and Hoyo, Cathrine and Allen, Terrence K.}, year={2023}, month={Jan} } @article{bukowski_hoyo_vielot_graff_kosorok_brewster_maguire_murphy_nedjai_ladoukakis_et al._2023, title={Epigenome-wide methylation and progression to high-grade cervical intraepithelial neoplasia (CIN2+): a prospective cohort study in the United States}, volume={23}, ISSN={["1471-2407"]}, DOI={10.1186/s12885-023-11518-6}, abstractNote={Abstract}, number={1}, journal={BMC CANCER}, author={Bukowski, Alexandra and Hoyo, Cathrine and Vielot, Nadja A. and Graff, Misa and Kosorok, Michael R. and Brewster, Wendy R. and Maguire, Rachel L. and Murphy, Susan K. and Nedjai, Belinda and Ladoukakis, Efthymios and et al.}, year={2023}, month={Nov} } @article{sosnowski_ellison-barnes_kaufman_hoyo_murphy_hernandez_marchesoni_klein_johnson_2023, title={Financial stress as a mediator of the association between maternal childhood adversity and infant birth weight, gestational age, and NICU admission}, volume={23}, ISSN={["1471-2458"]}, DOI={10.1186/s12889-023-15495-0}, abstractNote={Abstract}, number={1}, journal={BMC PUBLIC HEALTH}, author={Sosnowski, David W. W. and Ellison-Barnes, Alejandra and Kaufman, Joan and Hoyo, Cathrine and Murphy, Susan K. K. and Hernandez, Raquel G. G. and Marchesoni, Joddy and Klein, Lauren M. M. and Johnson, Sara B.}, year={2023}, month={Mar} } @article{sosnowski_ellison-barnes_kaufman_hoyo_murphy_hernandez_marchesoni_klein_johnson_2023, title={Financial stress as a mediator of the association between maternal childhood adversity and infant birth weight, gestational age, and NICU admission (vol 23, 606, 2023)}, volume={23}, ISSN={["1471-2458"]}, DOI={10.1186/s12889-023-15783-9}, number={1}, journal={BMC PUBLIC HEALTH}, author={Sosnowski, David W. and Ellison-Barnes, Alejandra and Kaufman, Joan and Hoyo, Cathrine and Murphy, Susan K. and Hernandez, Raquel G. and Marchesoni, Joddy and Klein, Lauren M. and Johnson, Sara B.}, year={2023}, month={May} } @article{choudhary_monasso_karhunen_ronkainen_mancano_howe_niu_zeng_guan_dou_et al._2023, title={Maternal educational attainment in pregnancy and epigenome-wide DNA methylation changes in the offspring from birth until adolescence}, volume={12}, ISSN={["1476-5578"]}, DOI={10.1038/s41380-023-02331-5}, abstractNote={Abstract}, journal={MOLECULAR PSYCHIATRY}, author={Choudhary, Priyanka and Monasso, Giulietta S. and Karhunen, Ville and Ronkainen, Justiina and Mancano, Giulia and Howe, Caitlin G. and Niu, Zhongzheng and Zeng, Xuehuo and Guan, Weihua and Dou, John and et al.}, year={2023}, month={Dec} } @article{fuemmeler_glasgow_schechter_maguire_sheng_bidopia_barsell_ksinan_zhang_lin_et al._2023, title={Prenatal and Childhood Smoke Exposure Associations with Cognition, Language, and Attention-Deficit/Hyperactivity Disorder}, volume={256}, ISSN={["1097-6833"]}, DOI={10.1016/j.jpeds.2022.11.041}, abstractNote={To assess the relationships of prenatal and childhood smoke exposure with specific neurodevelopmental and behavioral problems during early childhood.A subsample (n = 386) of mother-child dyads from the Newborn Epigenetic Study (NEST) prebirth cohort participated in the study. Cotinine concentrations were used to objectively measure prenatal and childhood smoke exposure when youth were aged 3-13 years. Multivariable regression models were used to estimate associations of prenatal and childhood cotinine concentrations with performance on the National Institutes of Health (NIH) Toolbox and attention-deficit/hyperactivity disorder and behavioral symptoms, measured using the Behavior Assessment System for Children, 2nd edition (BASC-2).After adjusting for confounders, childhood cotinine concentrations were associated with poorer cognitive performance on tasks measuring cognitive flexibility (B = -1.29; P = .03), episodic memory (B = -0.97; P = .02), receptive language development (B = -0.58; P = .01), and inhibitory control and attention (B = -1.59; P = .006). Although childhood cotinine concentration was associated with higher levels of attention problems (B = 0.83; P = .004) on the BASC-2, after adjustment for confounders, the association is nonsignificant. Although associations for maternal cotinine concentrations were null, an interaction was detected between prenatal and childhood cotinine concentrations on the NIH Toolbox Picture Vocabulary Task (P = .02).Our findings suggest that childhood tobacco smoke exposure may lead to poorer attention regulation and language acquisition, complex visual processing ability, and attention problems.}, journal={JOURNAL OF PEDIATRICS}, author={Fuemmeler, Bernard F. and Glasgow, Trevin E. and Schechter, Julia C. and Maguire, Rachel and Sheng, Yaou and Bidopia, Tatyana and Barsell, D. Jeremy and Ksinan, Albert and Zhang, Junfeng and Lin, Yan and et al.}, year={2023}, month={May}, pages={77-+} } @article{haight_maselko_ghastine_hoyo_martin_2023, title={Residential segregation and prenatal depression in a non-Hispanic Black and Hispanic cohort in North Carolina}, volume={83}, ISSN={["1873-2585"]}, DOI={10.1016/j.annepidem.2023.04.015}, abstractNote={Investigate residential segregation and prenatal depression in a non-Hispanic (NH) Black and Hispanic North Carolina pregnancy cohort.Demographics, prenatal depression (Center for Epidemiological Studies Depression scale ≥16), and residence from the 2006-2009 Newborn Epigenetic Survey were linked to Census-tract levels of racial and economic segregation (Index of Concentration at the Extremes) from the American Community Survey 2005-2009 5-year estimates. Adjusted prevalence ratios (aPR) for prenatal depression compared living in Index of Concentration at the Extremes tertiles 1 and 2 (higher proportion NH Black or Hispanic and/or low income) to 3 (higher proportion NH white and/or high-income), accounting for neighborhood clustering, age, education, employment, parity, and marital status.Among the 773 survey participants (482 NH Black and 291 Hispanic), 35.7% and 27.2% of NH Black and Hispanic participants had prenatal depression, respectively. For NH Black participants, depression prevalence was 17% lower for tertile 1 versus 3 for the NH Black/white (aPR=0.83; 95% CI=0.62-1.10), low/high income (aPR=0.83; 95% CI=0.62-1.11), and low-income NH Black/high-income NH white (aPR=0.82; 95% CI=0.61-1.09) measures. For Hispanic participants, estimates were weaker in the opposite direction for the Hispanic/NH white (aPR=1.02; 95% CI=0.71-1.47), low/high income (aPr=1.14; (95% CI=0.76-1.69), and low-income Hispanic/high-income NH white (aPR=1.12; 95% CI=0.78-1.60) measures.Residential segregation's impact on prenatal depression may differ by race/ethnicity and level of segregation, but findings are imprecise due to small sample sizes. Longitudinal research spanning greater geographic areas is needed.}, journal={ANNALS OF EPIDEMIOLOGY}, author={Haight, Sarah C. and Maselko, Joanna and Ghastine, Lea and Hoyo, Cathrine and Martin, Chantel L.}, year={2023}, month={Jul}, pages={15–22} } @article{moylan_mavis_jima_maguire_bashir_hyun_cabezas_parish_niedzwiecki_diehl_et al._2022, title={Alterations in DNA methylation associate with fatty liver and metabolic abnormalities in a multi-ethnic cohort of pre-teenage children}, ISSN={["1559-2308"]}, DOI={10.1080/15592294.2022.2039850}, abstractNote={ABSTRACT Non-Alcoholic fatty liver disease (NAFLD) is the leading cause of chronic liver disease in children. Epigenetic alterations, such as through DNA methylation (DNAm), may link adverse childhood exposures and fatty liver and provide non-invasive methods for identifying children at high risk for NAFLD and associated metabolic dysfunction. We investigated the association between differential DNAm and liver fat content (LFC) and liver injury in pre-adolescent children. Leveraging data from the Newborn Epigenetics Study (NEST), we enrolled 90 mother-child dyads and used linear regression to identify CpG sites and differentially methylated regions (DMRs) in peripheral blood associated with LFC and alanine aminotransferase (ALT) levels in 7–12yo children. DNAm was measured using Infinium HumanMethylationEPIC BeadChips (Illumina). LFC and fibrosis were quantified by magnetic resonance imaging proton density fat fraction and elastography. Median LFC was 1.4% (range, 0.3–13.4%) and MRE was 2.5 kPa (range, 1.5–3.6kPa). Three children had LFC ≥ 5%, while six (7.6%) met our definition of NAFLD (LFC ≥ 3.7%). All children with NAFLD were obese and five were Black. LFC was associated with 88 DMRs and 106 CpGs (FDR<5%). The top two CpGs, cg25474373 and cg07264203, mapped to or near RFTN2 and PRICKLE2 genes. These two CpG sites were also significantly associated with a NAFLD diagnosis. As higher LFC associates with an adverse cardiometabolic profile already in childhood, altered DNAm may identify these children early in disease course for targeted intervention. Larger, longitudinal studies are needed to validate these findings and determine mechanistic relevance.}, journal={EPIGENETICS}, author={Moylan, Cynthia A. and Mavis, Alisha M. and Jima, Dereje and Maguire, Rachel and Bashir, Mustafa and Hyun, Jeongeun and Cabezas, Melanie N. and Parish, Alice and Niedzwiecki, Donna and Diehl, Anna Mae and et al.}, year={2022}, month={Feb} } @article{gonzalez-nahm_ostbye_hoyo_kravitz_benjamin-neelon_2022, title={Associations Among Food Security, Diet Quality, and Dietary Intake During Pregnancy in a Predominantly African American Group of Women from North Carolina}, volume={122}, ISSN={["2212-2680"]}, DOI={10.1016/j.j.2021.08.110}, number={3}, journal={JOURNAL OF THE ACADEMY OF NUTRITION AND DIETETICS}, author={Gonzalez-Nahm, Sarah and Ostbye, Truls and Hoyo, Cathrine and Kravitz, Richard M. and Benjamin-Neelon, Sara E.}, year={2022}, month={Mar}, pages={565–572} } @article{lloyd_skinner_maguire_murphy_motsinger-reif_hoyo_house_2022, title={Clomifene and Assisted Reproductive Technology in Humans Are Associated with Sex-Specific Offspring Epigenetic Alterations in Imprinted Control Regions}, volume={23}, ISSN={["1422-0067"]}, url={https://doi.org/10.3390/ijms231810450}, DOI={10.3390/ijms231810450}, abstractNote={Children conceived with assisted reproductive technology (ART) have an increased risk of adverse outcomes, including congenital malformations and imprinted gene disorders. In a retrospective North Carolina-based-birth-cohort, we examined the effect of ovulation drugs and ART on CpG methylation in differentially methylated CpGs in known imprint control regions (ICRs). Nine ICRs containing 48 CpGs were assessed for methylation status by pyrosequencing in mixed leukocytes from cord blood. After restricting to non-smoking, college-educated participants who agreed to follow-up, ART-exposed (n = 27), clomifene-only-exposed (n = 22), and non-exposed (n = 516) groups were defined. Associations of clomifene and ART with ICR CpG methylation were assessed with linear regression and stratifying by offspring sex. In males, ART was associated with hypomethylation of the PEG3 ICR [β(95% CI) = −1.46 (−2.81, −0.12)] and hypermethylation of the MEG3 ICR [3.71 (0.01, 7.40)]; clomifene-only was associated with hypomethylation of the NNAT ICR [−5.25 (−10.12, −0.38)]. In female offspring, ART was associated with hypomethylation of the IGF2 ICR [−3.67 (−6.79, −0.55)]. Aberrant methylation of these ICRs has been associated with cardiovascular disease and metabolic and behavioral outcomes in children. The results suggest that the increased risk of adverse outcomes in offspring conceived through ART may be due in part to altered methylation of ICRs. Larger studies utilizing epigenome-wide interrogation are warranted.}, number={18}, journal={INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES}, author={Lloyd, Dillon T. and Skinner, Harlyn G. and Maguire, Rachel and Murphy, Susan K. and Motsinger-Reif, Alison A. and Hoyo, Cathrine and House, John S.}, year={2022}, month={Sep} } @article{jima_skaar_planchart_motsinger-reif_cevik_park_cowley_wright_house_liu_et al._2022, title={Genomic map of candidate human imprint control regions: the imprintome}, volume={6}, ISSN={["1559-2308"]}, url={https://doi.org/10.1080/15592294.2022.2091815}, DOI={10.1080/15592294.2022.2091815}, abstractNote={ABSTRACT Imprinted genes – critical for growth, metabolism, and neuronal function – are expressed from one parental allele. Parent-of-origin-dependent CpG methylation regulates this expression at imprint control regions (ICRs). Since ICRs are established before tissue specification, these methylation marks are similar across cell types. Thus, they are attractive for investigating the developmental origins of adult diseases using accessible tissues, but remain unknown. We determined genome-wide candidate ICRs in humans by performing whole-genome bisulphite sequencing (WGBS) of DNA derived from the three germ layers and from gametes. We identified 1,488 hemi-methylated candidate ICRs, including 19 of 25 previously characterized ICRs (https://humanicr.org/). Gamete methylation approached 0% or 100% in 332 ICRs (178 paternally and 154 maternally methylated), supporting parent-of-origin-specific methylation, and 65% were in well-described CTCF-binding or DNaseI hypersensitive regions. This draft of the human imprintome will allow for the systematic determination of the role of early-acquired imprinting dysregulation in the pathogenesis of human diseases and developmental and behavioural disorders.}, journal={EPIGENETICS}, author={Jima, Dereje D. and Skaar, David A. and Planchart, Antonio and Motsinger-Reif, Alison and Cevik, Sebnem E. and Park, Sarah S. and Cowley, Michael and Wright, Fred and House, John and Liu, Andy and et al.}, year={2022}, month={Jun} } @article{lodge_haji-noor_gutierrez_aiello_hoyo_emch_martin_2022, title={Gestational exposure to neighborhood police-reported crime and early childhood blood pressure in Durham, NC}, volume={75}, ISSN={["1873-2054"]}, DOI={10.1016/j.healthplace.2022.102800}, abstractNote={Gestational exposure to police-reported crime is associated with adverse birth outcomes, but no previous research has evaluated the effects of gestational crime exposure on early childhood health or attempted to disentangle the health effects of neighborhood crime from the effects of neighborhood policing. Using data from 672 Newborn Epigenetics Study participants, we evaluate the effects of gestational exposure to violent crime and racialized drug policing on early childhood blood pressure. We demonstrate that violence and drug policing are consistently associated with increased blood pressure among children born to Black participants but not White or Latinx participants.}, journal={HEALTH & PLACE}, author={Lodge, Evans K. and Haji-Noor, Zakiya and Gutierrez, Carmen M. and Aiello, Allison E. and Hoyo, Cathrine and Emch, Michael E. and Martin, Chantel L.}, year={2022}, month={May} } @article{gonzalez-nahm_marchesoni_maity_maguire_house_tucker_atkinson_murphy_hoyo_2022, title={Maternal Mediterranean Diet Adherence and Its Associations with Maternal Prenatal Stressors and Child Growth}, volume={6}, ISSN={["2475-2991"]}, DOI={10.1093/cdn/nzac146}, abstractNote={ABSTRACT Background Psychosocial and physiologic stressors, such as depression and obesity, during pregnancy can have negative consequences, such as increased systemic inflammation, contributing to chronic disease for both mothers and their unborn children. These conditions disproportionately affect racial/ethnic minorities. The effects of recommended dietary patterns in mitigating the effects of these stressors remain understudied. Objectives We aimed to evaluate the relations between maternal Mediterranean diet adherence (MDA) and maternal and offspring outcomes during the first decade of life in African Americans, Hispanics, and Whites. Methods This study included 929 mother–child dyads from the NEST (Newborn Epigenetics STudy), a prospective cohort study. FFQs were used to estimate MDA in pregnant women. Weight and height were measured in children between birth and age 8 y. Multivariable linear regression models were used to examine associations between maternal MDA, inflammatory cytokines, and pregnancy and postnatal outcomes. Results More than 55% of White women reported high MDA during the periconceptional period compared with 22% of Hispanic and 18% of African American women (P < 0.05). Higher MDA was associated with lower likelihood of depressive mood (β = −0.45; 95% CI: −0.90, −0.18; P = 0.02) and prepregnancy obesity (β = −0.29; 95% CI: −0.57, −0.0002; P = 0.05). Higher MDA was also associated with lower body size at birth, which was maintained to ages 3–5 and 6–8 y—this association was most apparent in White children (3–5 y: β = −2.9, P = 0.02; 6–8 y: β = −3.99, P = 0.01). Conclusions If replicated in larger studies, our data suggest that MDA provides a potent avenue by which effects of prenatal stressors on maternal and fetal outcomes can be mitigated to reduce ethnic disparities in childhood obesity.}, number={11}, journal={CURRENT DEVELOPMENTS IN NUTRITION}, author={Gonzalez-Nahm, Sarah and Marchesoni, Joddy and Maity, Arnab and Maguire, Rachel L. and House, John S. and Tucker, Rachel and Atkinson, Tamara and Murphy, Susan K. and Hoyo, Cathrine}, year={2022}, month={Nov} } @article{joglekar_grenier_hoyo_hoffman_murphy_2022, title={Maternal tobacco smoke exposure is associated with increased DNA methylation at human metastable epialleles in infant cord blood}, volume={8}, ISSN={["2058-5888"]}, DOI={10.1093/eep/dvac005}, abstractNote={Abstract}, number={1}, journal={ENVIRONMENTAL EPIGENETICS}, author={Joglekar, Rashmi and Grenier, Carole and Hoyo, Cathrine and Hoffman, Kate and Murphy, Susan K.}, year={2022}, month={Mar} } @misc{solomon_huen_yousefi_kupers_gonzalez_suderman_reese_page_gruzieva_rzehak_et al._2022, title={Meta-analysis of epigenome-wide association studies in newborns and children show widespread sex differences in blood DNA methylation}, volume={789}, ISSN={["1388-2139"]}, DOI={10.1016/j.mrrev.2022.108415}, abstractNote={Among children, sex-specific differences in disease prevalence, age of onset, and susceptibility have been observed in health conditions including asthma, immune response, metabolic health, some pediatric and adult cancers, and psychiatric disorders. Epigenetic modifications such as DNA methylation may play a role in the sexual differences observed in diseases and other physiological traits.We performed a meta-analysis of the association of sex and cord blood DNA methylation at over 450,000 CpG sites in 8438 newborns from 17 cohorts participating in the Pregnancy And Childhood Epigenetics (PACE) Consortium. We also examined associations of child sex with DNA methylation in older children ages 5.5-10 years from 8 cohorts (n = 4268).In newborn blood, sex was associated at Bonferroni level significance with differences in DNA methylation at 46,979 autosomal CpG sites (p < 1.3 × 10-7) after adjusting for white blood cell proportions and batch. Most of those sites had lower methylation levels in males than in females. Of the differentially methylated CpG sites identified in newborn blood, 68% (31,727) met look-up level significance (p < 1.1 × 10-6) in older children and had methylation differences in the same direction.This is a large-scale meta-analysis examining sex differences in DNA methylation in newborns and older children. Expanding upon previous studies, we replicated previous findings and identified additional autosomal sites with sex-specific differences in DNA methylation. Differentially methylated sites were enriched in genes involved in cancer, psychiatric disorders, and cardiovascular phenotypes.}, journal={MUTATION RESEARCH-REVIEWS IN MUTATION RESEARCH}, author={Solomon, Olivia and Huen, Karen and Yousefi, Paul and Kupers, Leanne K. and Gonzalez, Juan R. and Suderman, Matthew and Reese, Sarah E. and Page, Christian M. and Gruzieva, Olena and Rzehak, Peter and et al.}, year={2022} } @article{wheeler_boyle_barsell_maguire_dahman_murphy_hoyo_zhang_oliver_mcclernon_et al._2022, title={Neighborhood Deprivation is Associated with Increased Risk of Prenatal Smoke Exposure}, ISSN={["1573-6695"]}, DOI={10.1007/s11121-022-01355-7}, abstractNote={Despite years of advisories against the behavior, smoking among pregnant women remains a persistent public health issue in the USA. Recent estimates suggest that 9.4% of women smoke before pregnancy and 7.1% during pregnancy in the USA. Epidemiological research has attempted to pinpoint individual-level and neighborhood-level factors for smoking during pregnancy, including educational attainment, employment status, housing conditions, poverty, and racial demographics. However, most of these studies have relied upon self-reported measures of smoking, which are subject to reporting bias. To more accurately and objectively assess smoke exposure in mothers during pregnancy, we used Bayesian index models to estimate a neighborhood deprivation index (NDI) for block groups in Durham County, North Carolina, and its association with cotinine, a marker of smoke exposure, in pregnant mothers (n = 887 enrolled 2005-2011). Results showed a significant positive association between NDI and log cotinine (beta = 0.20, 95% credible interval = [0.11, 0.29]) after adjusting for individual covariates (e.g., race/ethnicity and education). The two most important variables in the NDI according to the estimated index weights were percent females without a high school degree and percent Black population. At the individual level, Hispanic and other race/ethnicity were associated with lowered cotinine compared with non-Hispanic Whites. Higher education levels were also associated with lowered cotinine. In summary, our findings provide stronger evidence that the socio-geographic variables of educational attainment and neighborhood racial composition are important factors for smoking and secondhand smoke exposure during pregnancy and can be used to target intervention efforts.}, journal={PREVENTION SCIENCE}, author={Wheeler, David C. and Boyle, Joseph and Barsell, D. Jeremy and Maguire, Rachel L. and Dahman, Bassam and Murphy, Susan K. and Hoyo, Cathrine and Zhang, Jim and Oliver, Jason A. and McClernon, Joseph and et al.}, year={2022}, month={Feb} } @misc{vidal_moylan_wilder_grant_murphy_hoyo_2022, title={Racial disparities in liver cancer: Evidence for a role of environmental contaminants and the epigenome}, volume={12}, ISSN={["2234-943X"]}, DOI={10.3389/fonc.2022.959852}, abstractNote={Liver cancer incidence has tripled since the early 1980s, making this disease one of the fastest rising types of cancer and the third leading cause of cancer-related deaths worldwide. In the US, incidence varies by geographic location and race, with the highest incidence in the southwestern and southeastern states and among racial minorities such as Hispanic and Black individuals. Prognosis is also poorer among these populations. The observed ethnic disparities do not fully reflect differences in the prevalence of risk factors, e.g., for cirrhosis that may progress to liver cancer or from genetic predisposition. Likely substantial contributors to risk are environmental factors, including chemical and non-chemical stressors; yet, the paucity of mechanistic insights impedes prevention efforts. Here, we review the current literature and evaluate challenges to reducing liver cancer disparities. We also discuss the hypothesis that epigenetic mediators may provide biomarkers for early detection to support interventions that reduce disparities.}, journal={FRONTIERS IN ONCOLOGY}, author={Vidal, Adriana C. C. and Moylan, Cynthia A. A. and Wilder, Julius and Grant, Delores J. J. and Murphy, Susan K. K. and Hoyo, Cathrine}, year={2022}, month={Aug} } @article{king_sparling_lloyd_satusky_martinez_grenier_bergemann_maguire_hoyo_meyer_et al._2022, title={Sex-specific DNA methylation and associations with in utero tobacco smoke exposure at nuclear-encoded mitochondrial genes}, ISSN={["1559-2308"]}, DOI={10.1080/15592294.2022.2043591}, abstractNote={ABSTRACT Sex-linked differences in mitochondrial ATP production, enzyme activities, and reactive oxygen species generation have been reported in multiple tissue and cell types. While the effects of reproductive hormones underlie many of these differences, regulation of sexually dimorphic mitochondrial function has not been fully characterized. We hypothesized that sex-specific DNA methylation contributes to sex-specific expression of nuclear genes that influence mitochondrial function. Herein, we analysed DNA methylation data specifically focused on nuclear-encoded mitochondrial genes in 191 males and 190 females. We found 596 differentially methylated sites (DMSs) (FDR p < 0.05), corresponding to 324 genes, with at least a 1% difference in methylation between sexes. To investigate the potential functional significance, we utilized gene expression microarray data. Of the 324 genes containing DMSs, 17 showed differences in gene expression by sex. Particularly striking was that ATP5G2, encoding subunit C of ATP synthase, contains seven DMSs and exhibits a sex difference in expression (p = 0.04). Finally, we also found that alterations in DNA methylation associated with in utero tobacco smoke exposure were sex-specific in these nuclear-encoded mitochondrial genes. Interestingly, the level of sex differences in DNA methylation at nuclear-encoded mitochondrial genes and the level of methylation changes associated with smoke exposure were less prominent than that of other genes. This suggests more conservative regulation of DNA methylation at these nuclear-encoded mitochondrial genes as compared to others. Overall, our findings suggest that sex-specific DNA methylation may help establish sex differences in expression and function and that sex-specific alterations in DNA methylation in response to exposures could contribute to sex-variable toxicological responses.}, journal={EPIGENETICS}, author={King, Dillon E. and Sparling, Anna Clare and Lloyd, Dillon and Satusky, Matthew Joseph and Martinez, Mackenzie and Grenier, Carole and Bergemann, Christina Michelle and Maguire, Rachel and Hoyo, Cathrine and Meyer, Joel Newman and et al.}, year={2022}, month={Mar} } @article{wheeler_boyle_barsell_maguire_zhang_oliver_jones_dahman_murphy_hoyo_et al._2022, title={Tobacco Retail Outlets, Neighborhood Deprivation and the Risk of Prenatal Smoke Exposure}, ISSN={["1469-994X"]}, DOI={10.1093/ntr/ntac164}, abstractNote={Abstract}, journal={NICOTINE & TOBACCO RESEARCH}, author={Wheeler, David C. and Boyle, Joseph and Barsell, D. Jeremy and Maguire, Rachel L. and Zhang, Junfeng and Oliver, Jason A. and Jones, Shawn and Dahman, Bassam and Murphy, Susan K. and Hoyo, Cathrine and et al.}, year={2022}, month={Jul} } @article{bosire_vidal_smith_jima_huang_skaar_valea_bentley_gradison_yarnall_et al._2021, title={Association between PEG3 DNA methylation and high-grade cervical intraepithelial neoplasia}, volume={16}, ISSN={["1750-9378"]}, DOI={10.1186/s13027-021-00382-3}, abstractNote={Abstract}, number={1}, journal={INFECTIOUS AGENTS AND CANCER}, author={Bosire, Claire and Vidal, Adriana C. and Smith, Jennifer S. and Jima, Dereje and Huang, Zhiqing and Skaar, David and Valea, Fidel and Bentley, Rex and Gradison, Margaret and Yarnall, Kimberly S. H. and et al.}, year={2021}, month={Jun} } @article{mueller_differding_ostbye_hoyo_benjamin-neelon_2021, title={Association of birth mode of delivery with infant faecal microbiota, potential pathobionts, and short chain fatty acids: a longitudinal study over the first year of life}, volume={128}, ISSN={["1471-0528"]}, DOI={10.1111/1471-0528.16633}, abstractNote={ObjectiveCaesarean section (CS) interrupts mother‐to‐newborn microbial transfer at birth. Beyond the neonatal period, the impact of CS on offspring gut microbiota and their short‐chain fatty acids (SCFAs) remains unclear. Here, we examine birth delivery mode (CS versus vaginal delivery) with the infant gut microbiota and faecal SCFAs measured 3 and 12 months after birth.}, number={8}, journal={BJOG-AN INTERNATIONAL JOURNAL OF OBSTETRICS AND GYNAECOLOGY}, author={Mueller, N. T. and Differding, M. K. and ostbye, T. and Hoyo, C. and Benjamin-Neelon, S. E.}, year={2021}, month={Jul}, pages={1293–1303} } @article{monangi_xu_khanam_khan_deb_pervin_price_kennedy_al mahmud_fan_et al._2021, title={Association of maternal prenatal selenium concentration and preterm birth: a multicountry meta-analysis}, volume={6}, ISSN={["2059-7908"]}, DOI={10.1136/bmjgh-2021-005856}, abstractNote={BackgroundSelenium (Se), an essential trace mineral, has been implicated in preterm birth (PTB). We aimed to determine the association of maternal Se concentrations during pregnancy with PTB risk and gestational duration in a large number of samples collected from diverse populations.}, number={9}, journal={BMJ GLOBAL HEALTH}, author={Monangi, Nagendra and Xu, Huan and Khanam, Rasheda and Khan, Waqasuddin and Deb, Saikat and Pervin, Jesmin and Price, Joan T. and Kennedy, Stephen H. and Al Mahmud, Abdullah and Fan, Yuemei and et al.}, year={2021}, month={Sep} } @article{maguire_house_lloyd_skinner_allen_raffi_skaar_park_mccullough_kollins_et al._2021, title={Associations between maternal obesity, gestational cytokine levels and child obesity in the NEST cohort}, volume={16}, ISSN={["2047-6302"]}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-85098446153&partnerID=MN8TOARS}, DOI={10.1111/ijpo.12763}, abstractNote={Summary}, number={7}, journal={PEDIATRIC OBESITY}, author={Maguire, Rachel L. and House, John S. and Lloyd, Dillon T. and Skinner, Harlyn G. and Allen, Terrence K. and Raffi, Asifa Mohamed and Skaar, David A. and Park, Sarah S. and McCullough, Lauren E. and Kollins, Scott H. and et al.}, year={2021}, month={Jul} } @article{fuemmeler_dozmorov_do_zhang_grenier_huang_maguire_kollins_hoyo_murphy_2021, title={DNA Methylation in Babies Born to Nonsmoking Mothers Exposed to Secondhand Smoke during Pregnancy: An Epigenome-Wide Association Study}, volume={129}, ISSN={["1552-9924"]}, DOI={10.1289/EHP8099}, abstractNote={Background: Maternal smoking during pregnancy is related to altered DNA methylation in infant umbilical cord blood. The extent to which low levels of smoke exposure among nonsmoking pregnant women relates to offspring DNA methylation is unknown. Objective: This study sought to evaluate relationships between maternal prenatal plasma cotinine levels and DNA methylation in umbilical cord blood in newborns using the Infinium HumanMethylation 450K BeadChip. Methods: Participants from the Newborn Epigenetics Study cohort who reported not smoking during pregnancy had verified low levels of cotinine from maternal prenatal plasma (0 ng/mL to <4 ng/mL), and offspring epigenetic data from umbilical cord blood were included in this study (n=79). Multivariable linear regression models were fit to the data, controlling for cell proportions, age, race, education, and parity. Estimates represent changes in response to any 1-ng/mL unit increase in exposure. Results: Multivariable linear regression models yielded 29,049 CpGs that were differentially methylated in relation to increases in cotinine at a 5% false discovery rate. Top CpGs were within or near genes involved in neuronal functioning (PRKG1, DLGAP2, BSG), carcinogenesis (FHIT, HSPC157) and inflammation (AGER). Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses suggest cotinine was related to methylation of gene pathways controlling neuronal signaling, metabolic regulation, cell signaling and regulation, and cancer. Further, enhancers associated with transcription start sites were enriched in altered CpGs. Using an independent sample from the same study population (n=115), bisulfite pyrosequencing was performed with infant cord blood DNA for two genes within our top 20 hits (AGER and PRKG1). Results from pyrosequencing replicated epigenome results for PRKG1 (cg17079497, estimate=−1.09, standard error (SE)=0.45, p=0.018) but not for AGER (cg09199225; estimate=−0.16, SE=0.21, p=0.44). Discussion: Secondhand smoke exposure among nonsmoking women may alter DNA methylation in regions involved in development, carcinogenesis, and neuronal functioning. These novel findings suggest that even low levels of smoke exposure during pregnancy may be sufficient to alter DNA methylation in distinct sites of mixed umbilical cord blood leukocytes in pathways that are known to be altered in cord blood from pregnant active smokers. https://doi.org/10.1289/EHP8099}, number={5}, journal={ENVIRONMENTAL HEALTH PERSPECTIVES}, author={Fuemmeler, Bernard F. and Dozmorov, Mikhail G. and Do, Elizabeth K. and Zhang, Junfeng and Grenier, Carole and Huang, Zhiqing and Maguire, Rachel L. and Kollins, Scott H. and Hoyo, Cathrine and Murphy, Susan K.}, year={2021}, month={May} } @article{lodge_hoyo_gutierrez_rappazzo_emch_martin_2021, title={Estimating exposure to neighborhood crime by race and ethnicity for public health research}, volume={21}, ISSN={["1471-2458"]}, DOI={10.1186/s12889-021-11057-4}, abstractNote={Abstract}, number={1}, journal={BMC PUBLIC HEALTH}, author={Lodge, Evans K. and Hoyo, Cathrine and Gutierrez, Carmen M. and Rappazzo, Kristen M. and Emch, Michael E. and Martin, Chantel L.}, year={2021}, month={Jun} } @article{ksinan_sheng_do_schechter_zhang_maguire_hoyo_murphy_kollins_rubin_et al._2021, title={Identifying the Best Questions for Rapid Screening of Secondhand Smoke Exposure Among Children}, volume={23}, ISSN={["1469-994X"]}, DOI={10.1093/ntr/ntaa254}, abstractNote={Abstract}, number={7}, journal={NICOTINE & TOBACCO RESEARCH}, author={Ksinan, Albert J. and Sheng, Yaou and Do, Elizabeth K. and Schechter, Julia C. and Zhang, Junfeng and Maguire, Rachel L. and Hoyo, Cathrine and Murphy, Susan K. and Kollins, Scott H. and Rubin, Bruce and et al.}, year={2021}, month={Jul}, pages={1217–1223} } @article{freedland_muller_hoyo_turner_moorman_faria_carvalhal_reis_mauad_carvalho_et al._2021, title={Implications of Regionalizing Care in the Developing World: Impact of Distance to Referral Center on Compliance to Biopsy Recommendations in a Brazilian Prostate Cancer Screening Cohort}, volume={2021}, ISSN={["2090-312X"]}, DOI={10.1155/2021/6614838}, abstractNote={Given growing specialization in medical care, optimal care may require regionalization, which may create access barriers. We tested this within a large prostate cancer (PC) screening program in Brazil. In 2004–2007, Barretos Cancer Hospital prospectively screened men for PC throughout rural Brazil. Men with abnormal screen were referred for follow-up and possible biopsy. We tested the link between distance from screening site to Barretos Cancer Hospital and risk of noncompliance with showing up for biopsy, PC on biopsy and, among those with PC, PC grade using crude and multivariable logistic regression analysis. Among 10,467 men undergoing initial screen, median distance was 257 km (IQR: 135–718 km). On crude and multivariable analyses, farther distance was significantly linked with biopsy noncompliance (OR/100 km: 0.83, P < 0.001 ). Among men who lived within 150 km of Barretos Cancer Hospital, distance was unrelated to compliance (OR/100 km: 1.09, P = 0.87 ). There was no association between distance and PC risk or PC grade (all P > 0.25 ). In Brazil, where distances to referral centers can be large, greater distance was related to reduced biopsy compliance in a PC screening cohort. Among men who lived within 150 km, distance was unrelated to compliance. Care regionalization may reduce access when distances are large.}, journal={PROSTATE CANCER}, author={Freedland, Alexis R. and Muller, Roberto L. and Hoyo, Cathrine and Turner, Elizabeth L. and Moorman, Patricia G. and Faria, Eliney F. and Carvalhal, Gustavo F. and Reis, Rodolfo B. and Mauad, Edmundo C. and Carvalho, Andre L. and et al.}, year={2021}, month={Jun} } @article{keyhan_burke_schrott_huang_grenier_price_raburn_corcoran_soubry_hoyo_et al._2021, title={Male obesity impacts DNA methylation reprogramming in sperm}, volume={13}, ISSN={["1868-7083"]}, DOI={10.1186/s13148-020-00997-0}, abstractNote={Abstract}, number={1}, journal={CLINICAL EPIGENETICS}, author={Keyhan, Sanaz and Burke, Emily and Schrott, Rose and Huang, Zhiqing and Grenier, Carole and Price, Thomas and Raburn, Doug and Corcoran, David L. and Soubry, Adelheid and Hoyo, Catherine and et al.}, year={2021}, month={Jan} } @article{soubry_murphy_vansant_he_price_hoyo_2021, title={Opposing Epigenetic Signatures in Human Sperm by Intake of Fast Food Versus Healthy Food}, volume={12}, ISSN={["1664-2392"]}, DOI={10.3389/fendo.2021.625204}, abstractNote={Animal experiments have demonstrated that diets high in fats create a harmful environment for developing sperm cells, contributing to impaired reproductive health and induced risk for chronic diseases in the next generation. Changes at the level of the epigenome have been suggested to underlie these observations. Human data are limited to verify this hypothesis. While we earlier demonstrated a link between male obesity and DNA methylation changes at imprinted genes in mature sperm cells and newborns, it is currently unknown if -or how- a paternal eating pattern (related to obesity) is related to indices for epigenetic inheritance. We here aim to examine a yet unexplored link between consumption of healthy (rich in vitamins and fibers) or unhealthy (“fast”) foods and methylation at imprint regulatory regions in DNA of sperm. We obtained semen and data from 67 men, as part of a North Carolina-based study: The Influence of the Environment on Gametic Epigenetic Reprogramming (TIEGER) study. Dietary data included intake of fruits/nuts, vegetables/soups, whole grain bread, meat, seafood/fish, and fatty or processed food items. Multiple regression models were used to explore the association between dietary habits and clinical sperm parameters as well as DNA methylation levels, quantified using bisulfite pyrosequencing at 12 differentially methylated regions (DMRs) of the following imprinted genes: GRB10, IGF2, H19, MEG3, NDN, NNAT, PEG1/MEST, PEG3, PLAGL1, SNRPN, and SGCE/PEG10. After adjusting for age, obesity status and recruitment method, we found that Total Motile Count (TMC) was significantly higher if men consumed fruits/nuts (β=+6.9, SE=1.9, p=0.0005) and vegetables (β=+5.4, SE=1.9, p=0.006), whereas consumption of fries was associated with lower TMC (β=-20.2, SE=8.7, p=0.024). Semen volume was also higher if vegetables or fruits/nuts were frequently consumed (β=+0.06, SE=0.03, p=0.03). Similarly, our sperm epigenetic analyses showed opposing associations for healthy versus fast food items. Frequent consumption of fries was related to a higher chance of sperm being methylated at the MEG3-IG CpG4 site (OR=1.073, 95%CI: 1.035-1.112), and high consumption of vegetables was associated with a lower risk of DNA methylation at the NNAT CpG3 site (OR=0.941, 95%CI: 0.914-0.968). These results remained significant after adjusting for multiple testing. We conclude that dietary habits are linked to sperm epigenetic outcomes. If carried into the next generation paternal unhealthy dietary patterns may result in adverse metabolic conditions and increased risk for chronic diseases in offspring. }, journal={FRONTIERS IN ENDOCRINOLOGY}, author={Soubry, Adelheid and Murphy, Susan K. and Vansant, Greet and He, Yang and Price, Thomas M. and Hoyo, Cathrine}, year={2021}, month={Apr} } @article{fallavollita_do_schechter_kollins_zheng_qin_maguire_hoyo_murphy_fuemmeler_2021, title={Smoke-Free Home Rules and Association with Child Secondhand Smoke Exposure among Mother-Child Dyad Relationships}, volume={18}, ISSN={["1660-4601"]}, DOI={10.3390/ijerph18105256}, abstractNote={Smoke-free home rules restrict smoking in the home, but biomarkers of secondhand smoke exposure are needed to help understand the association between smoke-free homes and child secondhand smoke exposure. Participants (n = 346) were majority Black/African American mother–child dyads from a longitudinal study in North Carolina. Mothers completed questionnaires on household smoking behaviors and rules, and child saliva samples were assayed for secondhand smoke exposure. Regression models used smoke-free home rules to predict child risk for secondhand smoke exposure. Children in households with smoke-free home rules had less salivary cotinine and risk for secondhand smoke exposure. After controlling for smokers in the household, home smoking rules were not a significant predictor of secondhand smoke exposure. Compared to children in households with no smokers, children in households with at least one smoker but a non-smoking mother (OR 5.35, 95% CI: 2.22, 13.17) and households with at least one smoker including a smoking mother (OR 13.73, 95% CI: 6.06, 33.28) had greater risk for secondhand smoke exposure. Results suggest smoke-free home rules are not sufficient to fully protect children from secondhand smoke exposure, especially in homes with smokers. Future research should focus on how household members who smoke can facilitate the prevention of child secondhand smoke exposure.}, number={10}, journal={INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH}, author={Fallavollita, Westley L. and Do, Elizabeth K. and Schechter, Julia C. and Kollins, Scott H. and Zheng, Junfeng and Qin, Jian and Maguire, Rachel L. and Hoyo, Cathrine and Murphy, Susan K. and Fuemmeler, Bernard F.}, year={2021}, month={May} } @article{neumann_walton_alemany_cecil_gonzalez_jima_lahti_tuominen_barker_binder_et al._2020, title={Association between DNA methylation and ADHD symptoms from birth to school age: a prospective meta-analysis}, volume={10}, ISSN={["2158-3188"]}, DOI={10.1038/s41398-020-01058-z}, abstractNote={Abstract}, number={1}, journal={TRANSLATIONAL PSYCHIATRY}, author={Neumann, Alexander and Walton, Esther and Alemany, Silvia and Cecil, Charlotte and Gonzalez, Juan Ramon and Jima, Dereje D. and Lahti, Jari and Tuominen, Samuli T. and Barker, Edward D. and Binder, Elisabeth and et al.}, year={2020}, month={Nov} } @article{gonzalez-nahm_nihlani_s. house_l. maguire_g. skinner_hoyo_2020, title={Associations between Maternal Cadmium Exposure with Risk of Preterm Birth and Low after Birth Weight Effect of Mediterranean Diet Adherence on Affected Prenatal Outcomes}, volume={8}, ISSN={["2305-6304"]}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-85094109102&partnerID=MN8TOARS}, DOI={10.3390/toxics8040090}, abstractNote={Prenatal cadmium exposure at non-occupational levels has been associated with poor birth outcomes. The intake of essential metals, such as iron and selenium, may mitigate cadmium exposure effects. However, at high levels, these metals can be toxic. The role of dietary patterns rich in these metals is less studied. We used a linear and logistic regression in a cohort of 185 mother–infant pairs to assess if a Mediterranean diet pattern during pregnancy modified the associations between prenatal cadmium exposure and (1) birth weight and (2) preterm birth. We found that increased cadmium exposure during pregnancy was associated with lower birth weight (β = −210.4; 95% CI: −332.0, −88.8; p = 0.008) and preterm birth (OR = 0.11; 95% CI: 0.01, 0.72; p = 0.04); however, these associations were comparable in offspring born to women reporting high adherence to a Mediterranean diet (β = −274.95; 95% CI: −701.17, 151.26; p = 0.20) and those with low adherence (β = −64.76; 95% CI: −359.90, 230.37; p = 0.66). While the small sample size limits inference, our findings suggest that adherence to a Mediterranean dietary pattern may not mitigate cadmium exposure effects. Given the multiple organs targeted by cadmium and its slow excretion rate, larger studies are required to clarify these findings.}, number={4}, journal={TOXICS}, publisher={MDPI AG}, author={Gonzalez-Nahm, Sarah and Nihlani, Kiran and S. House, John and L. Maguire, Rachel and G. Skinner, Harlyn and Hoyo, Cathrine}, year={2020}, month={Dec} } @article{fuemmeler_sheng_schechter_do_zucker_majors_maguire_murphy_hoyo_kollins_2020, title={Associations between attention deficit hyperactivity disorder symptoms and eating behaviors in early childhood}, volume={15}, ISSN={["2047-6302"]}, DOI={10.1111/ijpo.12631}, abstractNote={Abstract}, number={7}, journal={PEDIATRIC OBESITY}, author={Fuemmeler, Bernard F. and Sheng, Yaou and Schechter, Julia C. and Do, Elizabeth and Zucker, Nancy and Majors, Alesha and Maguire, Rachel and Murphy, Susan K. and Hoyo, Cathrine and Kollins, Scott H.}, year={2020}, month={Jul} } @article{vehmeijer_kuepers_sharp_salas_lent_jima_tindula_reese_qi_gruzieva_et al._2020, title={DNA methylation and body mass index from birth to adolescence: meta-analyses of epigenome-wide association studies}, volume={12}, ISSN={["1756-994X"]}, DOI={10.1186/s13073-020-00810-w}, abstractNote={Abstract}, number={1}, journal={GENOME MEDICINE}, author={Vehmeijer, Florianne O. L. and Kuepers, Leanne K. and Sharp, Gemma C. and Salas, Lucas A. and Lent, Samantha and Jima, Dereje D. and Tindula, Gwen and Reese, Sarah and Qi, Cancan and Gruzieva, Olena and et al.}, year={2020}, month={Dec} } @article{benjamin-neelon_iversen_clancy_hoyo_bennett_kravitz_ostbye_2020, title={Early Child Care and Weight Status in a Cohort of Predominantly Black Infants in the Southeastern United States}, volume={16}, ISSN={["2153-2176"]}, DOI={10.1089/chi.2019.0127}, abstractNote={Background: Previous studies show inconsistent relations between child care and obesity, but few assessed longitudinal associations during infancy and even fewer included racially diverse children. We examined associations of time infants spent in child care, both overall and in different types of care, with weight status at 6 and 12 months. Methods: We examined 664 infants living in central North Carolina. We conducted adjusted multivariable linear regressions examining (1) child care from birth to 6 months and 6-month weight-for-length (WFL) z-score, and (2) child care from birth to 12 months and 12-month WFL z-score. We assessed any child care and child care by type, including relative care, informal care by a nonrelative, formal child care, and a combination of care (e.g., relative and informal care). Results: Nearly 70% of infants were black and 49% were female. After adjustment for potential confounders, any child care was not associated with WFL z-score at 6 months (0.07; 95% confidence intervals [CI] -0.02 to 0.16; p = 0.13) or 12 months (0.05; 95% CI -0.02 to 0.12; p = 0.19). However, greater combination care was associated with higher WFL z-score at 6 months (0.68; 95% CI 0.23-1.13; p = 0.003) and greater care by a relative was associated with higher WFL z-score at 12 months (0.16; 95% CI 0.05-0.26; p = 0.005). Conclusions: Although we did not observe associations with any child care, combination care and relative care during infancy were associated with higher weight. Interventions aimed at preventing excessive weight gain in early life may target relatives who provide regular care for infants.}, number={2}, journal={CHILDHOOD OBESITY}, author={Benjamin-Neelon, Sara E. and Iversen, Edwin and Clancy, Shayna M. and Hoyo, Cathrine and Bennett, Gary G. and Kravitz, Richard M. and Ostbye, Truls}, year={2020}, month={Mar}, pages={122–128} } @article{schechter_do_zhang_hoyo_murphy_kollins_fuemmeler_2020, title={Effect of Prenatal Smoke Exposure on Birth Weight: The Moderating Role of Maternal Depressive Symptoms}, volume={22}, ISSN={["1469-994X"]}, DOI={10.1093/ntr/nty267}, abstractNote={Abstract}, number={1}, journal={NICOTINE & TOBACCO RESEARCH}, author={Schechter, Julia C. and Do, Elizabeth K. and Zhang, Junfeng and Hoyo, Cathrine and Murphy, Susan K. and Kollins, Scott H. and Fuemmeler, Bernard F.}, year={2020}, month={Jan}, pages={40–47} } @article{shafiee-kermani_carney_jima_utin_farrar_oputa_hines_kinyamu_trotter_archer_et al._2020, title={Expression of UDP Glucuronosyltransferases2B15and2B17is associated with methylation status in prostate cancer cells}, ISBN={1559-2308}, DOI={10.1080/15592294.2020.1795601}, abstractNote={ABSTRACT Studies have suggested that abrogated expression of detoxification enzymes, UGT2B15 and UGT2B17, are associated with prostate tumour risk and progression. We investigated the role of EGF on the expression of these enzymes since it interacts with signalling pathways to also affect prostate tumour progression and is additionally associated with decreased DNA methylation. The expression of UGT2B15, UGT2B17, de novo methyltransferases, DNMT3A and DNMT3B was assessed in prostate cancer cells (LNCaP) treated with EGF, an EGFR inhibitor PD16893, and the methyltransferase inhibitor, 5-azacytidine, respectively. The results showed that EGF treatment decreased levels of expression of all four genes and that their expression was reversed by PD16893. Treatment with 5-azacytidine, markedly decreased expression of UGT2B15 and UGT2B17 over 85% as well as significantly decreased expression of DNMT3B, but not the expression of DNMT3A. DNMT3B siRNA treated LNCaP cells had decreased expression of UGT2B15 and UGT2B17, while DNMT3A siRNA treated cells had only moderately decreased UGT2B15 expression. Treatment with DNMT methyltransferase inhibitor, RG108, significantly decreased UGT2B17 expression. Additionally, methylation differences between prostate cancer samples and benign prostate samples from an Illumina 450K Methylation Array study were assessed. The results taken together suggest that hypomethylation of the UGT2B15 and UGT2B17 genes contributes to increased risk of prostate cancer and may provide a putative biomarker or epigenetic target for chemotherapeutics. Mechanistic studies are warranted to determine the role of the methylation marks in prostate cancer.}, journal={EPIGENETICS}, author={Shafiee-Kermani, Farideh and Carney, Skyla T. and Jima, Dereje and Utin, Utibe C. and Farrar, LaNeisha B. and Oputa, Melvin O. and Hines, Marcono R., Jr. and Kinyamu, H. Karimi and Trotter, Kevin W. and Archer, Trevor K. and et al.}, year={2020} } @article{oddo_hoyo_ostbye_benjamin-neelon_2020, title={Maternal Employment and Infant BMI z Score in a US Birth Cohort}, volume={28}, ISSN={["1930-739X"]}, DOI={10.1002/oby.23009}, abstractNote={ObjectiveThe purpose of this study was to investigate the association between maternal employment and infant BMI z score.}, number={12}, journal={OBESITY}, author={Oddo, Vanessa M. and Hoyo, Cathrine and Ostbye, Truls and Benjamin-Neelon, Sara E.}, year={2020}, month={Dec}, pages={2389–2396} } @article{york_latendresse_jackson-cook_lapato_moyer_wolen_roberson-nay_do_murphy_hoyo_et al._2020, title={Replicated umbilical cord blood DNA methylation loci associated with gestational age at birth}, volume={15}, ISSN={["1559-2308"]}, DOI={10.1080/15592294.2020.1767277}, abstractNote={DNA methylation is highly sensitive to in utero perturbations and has an established role in both embryonic development and regulation of gene expression. The foetal genetic component has been previously shown to contribute significantly to the timing of birth, yet little is known about the identity and behaviour of individual genes. The aim of this study was to test the extent genome-wide DNA methylation levels in umbilical cord blood were associated with gestational age at birth (GA). Findings were validated in an independent sample and evidence for the regulation of gene expression was evaluated for cis gene relationships in specimens with multi-omic data. Genome-wide DNA methylation, measured by the Illumina Infinium Human Methylation 450 K BeadChip, was associated with GA for 2,372 CpG probes (5% FDR) in both the Pregnancy, Race, Environment, Genes (PREG) and Newborn Epigenetic Study (NEST) cohorts. Significant probes mapped to 1,640 characterized genes and an association with nearby gene expression measures obtained by the Affymetrix HG-133A microarray was found for 11 genes. Differentially methylated positions were enriched for actively transcribed and enhancer chromatin states, were predominately located outside of CpG islands, and mapped to genes enriched for inflammation and innate immunity ontologies. In both PREG and NEST, the first principal component derived from these probes explained approximately one-half (58.1% and 47.8%, respectively) of the variation in GA. Gene pathways identified are consistent with the hypothesis of pathogen detection and response by the immune system to elicit premature labour as a consequence of unscheduled inflammation.}, number={11}, journal={EPIGENETICS}, author={York, Timothy P. and Latendresse, Shawn J. and Jackson-Cook, Colleen and Lapato, Dana M. and Moyer, Sara and Wolen, Aaron R. and Roberson-Nay, Roxann and Do, Elizabeth K. and Murphy, Susan K. and Hoyo, Catherine and et al.}, year={2020}, month={Nov}, pages={1243–1258} } @article{huang_tzeng_maguire_hoyo_allen_2020, title={The association between neuraxial anesthesia and the development of childhood asthma - a secondary analysis of the newborn epigenetics study cohort}, volume={36}, ISSN={["1473-4877"]}, DOI={10.1080/03007995.2020.1747417}, abstractNote={Abstract Objectives Childhood asthma is a common chronic illness that has been associated with mode of delivery. However, the effect of cesarean delivery alone does not fully account for the increased prevalence of childhood asthma. We tested the hypothesis that neuraxial anesthesia used for labor analgesia and cesarean delivery alters the risk of developing childhood asthma. Methods Within the Newborn Epigenetics Study birth cohort, 196 mother and child pairs with entries in the electronic anesthesia records were included. From these records, data on maternal anesthesia type, duration of exposure, and drugs administered peripartum were abstracted and combined with questionnaire-derived prenatal risk factors and medical records and questionnaire-derived asthma diagnosis data in children. Logistic regression models were used to evaluate associations between type of anesthesia, duration of anesthesia, and the development of asthma in males and females. Results We found that longer duration of epidural anesthesia was associated with a lower risk of asthma in male children (OR = 0.80; 95% CI = 0.66–0.95) for each hour of epidural exposure. Additionally, a unit increase in the composite dose of local anesthetics and opioid analgesics administered via the spinal route was associated with a lower risk of asthma in both male (OR = 0.59, 95% CI = 0.36–0.96) and female children (OR 0.26, 95% CI 0.09–0.82). Conclusion Our data suggest that peripartum exposure to neuraxial anesthesia may reduce the risk of childhood asthma primarily in males. Larger human studies and model systems with longer follow-up are required to elucidate these findings.}, number={6}, journal={CURRENT MEDICAL RESEARCH AND OPINION}, author={Huang, Yueyang and Tzeng, Jung-Ying and Maguire, Rachel and Hoyo, Cathrine and Allen, Terrence}, year={2020}, month={Jun}, pages={1025–1032} } @article{differding_benjamin-neelon_hoyo_ostbye_mueller_2020, title={Timing of complementary feeding is associated with gut microbiota diversity and composition and short chain fatty acid concentrations over the first year of life}, volume={20}, ISSN={["1471-2180"]}, DOI={10.1186/s12866-020-01723-9}, abstractNote={Abstract}, number={1}, journal={BMC MICROBIOLOGY}, author={Differding, Moira K. and Benjamin-Neelon, Sara E. and Hoyo, Cathrine and ostbye, Truls and Mueller, Noel T.}, year={2020}, month={Mar} } @article{zhang_differding_benjamin-neelon_ostbye_hoyo_mueller_2019, title={Association of prenatal antibiotics with measures of infant adiposity and the gut microbiome}, volume={18}, ISSN={["1476-0711"]}, DOI={10.1186/s12941-019-0318-9}, abstractNote={Prenatal antibiotic exposure has been associated with an altered infant gut microbiome composition and higher risk of childhood obesity, but no studies have examined if prenatal antibiotics simultaneously alter the gut microbiome and adiposity in infants. In this prospective study (Nurture: recruitment 2013–2015 in North Carolina, United States), we examined in 454 infants the association of prenatal antibiotic exposure (by any prenatal antibiotic exposure; by trimester of pregnancy; by number of courses; by type of antibiotics) with infant age- and sex-specific weight-for-length z score (WFL-z) and skinfold thicknesses (subscapular, triceps, abdominal) at 12 months of age. In a subsample, we also examined whether prenatal antibiotic exposure was associated with alterations in the infant gut microbiome at ages 3 and 12 months. Compared to infants not exposed to prenatal antibiotics, infants who were exposed to any prenatal antibiotics had 0.21 (95% confidence interval [CI] 0.02, 0.41) higher WFL-z at 12 months, and 0.28 (95% CI 0.02, 0.55) higher WFL-z if they were exposed to antibiotics in the second trimester, after adjustment for potential confounders, birth weight, and gestational age. We also observed a dose-dependent association (P-value for trend = 0.006) with infants exposed to ≥ 3 courses having 0.41 (95% CI 0.13, 0.68) higher WFL-z at 12 months. After further adjustment for delivery method, only second-trimester antibiotic exposure remained associated with higher infant WFL-z (0.27, 95% CI 0.003, 0.54) and subscapular skinfold thickness (0.49 mm, 95% CI 0.11, 0.88) at 12 months. Infants exposed to second-trimester antibiotics versus not had differential abundance of 13 bacterial amplicon sequence variants (ASVs) at age 3 months and 17 ASVs at 12 months (false discovery rate adjusted P-value < 0.05). Prenatal antibiotic exposure in the second trimester was associated with an altered infant gut microbiome composition at 3 and 12 months and with higher infant WFL-z and subscapular skinfold thickness at 12 months.}, journal={ANNALS OF CLINICAL MICROBIOLOGY AND ANTIMICROBIALS}, author={Zhang, Mingyu and Differding, Moira K. and Benjamin-Neelon, Sara E. and Ostbye, Truls and Hoyo, Cathrine and Mueller, Noel T.}, year={2019}, month={Jun} } @article{howe_zhou_wang_pittman_thompson_campbell_bastain_grubbs_salam_hoyo_et al._2019, title={Associations between Maternal Tobacco Smoke Exposure and the Cord Blood CD4(+) DNA Methylome}, volume={127}, ISSN={["1552-9924"]}, DOI={10.1289/EHP3398}, abstractNote={Background: Maternal tobacco smoke exposure has been associated with altered DNA methylation. However, previous studies largely used methylation arrays, which cover a small fraction of CpGs, and focused on whole cord blood. Objectives: The current study examined the impact of in utero exposure to maternal tobacco smoke on the cord blood CD4+ DNA methylome. Methods: The methylomes of 20 Hispanic white newborns (n=10 exposed to any maternal tobacco smoke in pregnancy; n=10 unexposed) from the Maternal and Child Health Study (MACHS) were profiled by whole-genome bisulfite sequencing (median coverage: 6.5×). Statistical analyses were conducted using the Regression Analysis of Differential Methylation (RADMeth) program because it performs well on low-coverage data (minimizes false positives and negatives). Results: We found that 10,381 CpGs were differentially methylated by tobacco smoke exposure [neighbor-adjusted p-values that are additionally corrected for multiple testing based on the Benjamini-Hochberg method for controlling the false discovery rate (FDR) (pFDR)<0.05]. From these CpGs, RADMeth identified 557 differentially methylated regions (DMRs) that were overrepresented (p<0.05) in important regulatory regions, including enhancers. Of nine DMRs that could be queried in a reduced representation bisulfite sequencing (RRBS) study of adult CD4+ cells (n=9 smokers; n=10 nonsmokers), four replicated (p<0.05). Additionally, a CpG in the promoter of SLC7A8 (percent methylation difference: −9.4% comparing exposed to unexposed) replicated (p<0.05) in an EPIC (Illumina) array study of cord blood CD4+ cells (n=14 exposed to sustained maternal tobacco smoke; n=16 unexposed) and in a study of adult CD4+ cells across two platforms (EPIC: n=9 smokers; n=11 nonsmokers; 450K: n=59 smokers; n=72 nonsmokers). Conclusions: Maternal tobacco smoke exposure in pregnancy is associated with cord blood CD4+ DNA methylation in key regulatory regions, including enhancers. While we used a method that performs well on low-coverage data, we cannot exclude the possibility that some results may be false positives. However, we identified a differentially methylated CpG in amino acid transporter SLC7A8 that is highly reproducible, which may be sensitive to cigarette smoke in both cord blood and adult CD4+ cells. https://doi.org/10.1289/EHP3398}, number={4}, journal={ENVIRONMENTAL HEALTH PERSPECTIVES}, author={Howe, Caitlin G. and Zhou, Meng and Wang, Xuting and Pittman, Gary S. and Thompson, Isabel J. and Campbell, Michelle R. and Bastain, Theresa M. and Grubbs, Brendan H. and Salam, Muhammad T. and Hoyo, Cathrine and et al.}, year={2019}, month={Apr} } @article{do_zucker_huang_schechter_kollins_maguire_murphy_hoyo_fuemmeler_2019, title={Associations between imprinted gene differentially methylated regions, appetitive traits and body mass index in children}, volume={14}, ISSN={["2047-6302"]}, DOI={10.1111/ijpo.12454}, abstractNote={Summary}, number={2}, journal={PEDIATRIC OBESITY}, author={Do, E. K. and Zucker, N. L. and Huang, Z. Y. and Schechter, J. C. and Kollins, S. H. and Maguire, R. L. and Murphy, S. K. and Hoyo, C. and Fuemmeler, B. F.}, year={2019}, month={Feb} } @article{gonzalez-nahm_hoyo_ostbye_neelon_allen_benjamin-neelon_2019, title={Associations of maternal diet with infant adiposity at birth, 6 months and 12 months}, volume={9}, ISSN={["2044-6055"]}, DOI={10.1136/bmjopen-2019-030186}, abstractNote={ObjectivesTo assess associations between maternal prenatal diet quality and infant adiposity.}, number={9}, journal={BMJ OPEN}, author={Gonzalez-Nahm, Sarah and Hoyo, Cathrine and Ostbye, Truls and Neelon, Brian and Allen, Carter and Benjamin-Neelon, Sara E.}, year={2019}, month={Sep} } @article{sikdar_joehanes_joubert_xu_vives-usano_rezwan_felix_ward_guan_richmond_et al._2019, title={Comparison of smoking-related DNA methylation between newborns from prenatal exposure and adults from personal smoking}, volume={11}, ISSN={["1750-192X"]}, DOI={10.2217/epi-2019-0066}, abstractNote={ Aim: Cigarette smoking influences DNA methylation genome wide, in newborns from pregnancy exposure and in adults from personal smoking. Whether a unique methylation signature exists for in utero exposure in newborns is unknown. Materials & methods: We separately meta-analyzed newborn blood DNA methylation (assessed using Illumina450k Beadchip), in relation to sustained maternal smoking during pregnancy (9 cohorts, 5648 newborns, 897 exposed) and adult blood methylation and personal smoking (16 cohorts, 15907 participants, 2433 current smokers). Results & conclusion: Comparing meta-analyses, we identified numerous signatures specific to newborns along with many shared between newborns and adults. Unique smoking-associated genes in newborns were enriched in xenobiotic metabolism pathways. Our findings may provide insights into specific health impacts of prenatal exposure on offspring. }, number={13}, journal={EPIGENOMICS}, author={Sikdar, Sinjini and Joehanes, Roby and Joubert, Bonnie R. and Xu, Cheng-Jian and Vives-Usano, Marta and Rezwan, Faisal I. and Felix, Janine F. and Ward, James M. and Guan, Weihua and Richmond, Rebecca C. and et al.}, year={2019}, month={Oct}, pages={1487–1500} } @article{xie_leung_chen_long_hoyo_ho_2019, title={Differential methylation values in differential methylation analysis}, volume={35}, ISSN={["1460-2059"]}, DOI={10.1093/bioinformatics/bty778}, abstractNote={Abstract}, number={7}, journal={BIOINFORMATICS}, author={Xie, Changchun and Leung, Yuet-Kin and Chen, Aimin and Long, Ding-Xin and Hoyo, Catherine and Ho, Shuk-Mei}, year={2019}, month={Apr}, pages={1094–1097} } @article{mueller_zhang_hoyo_ostbye_benjamin-neelon_2019, title={Does cesarean delivery impact infant weight gain and adiposity over the first year of life?}, volume={43}, ISSN={["1476-5497"]}, DOI={10.1038/s41366-018-0239-2}, abstractNote={Potentially driven by the lack of mother-to-infant transmission of microbiota at birth, cesarean delivery has been associated with higher risk of offspring obesity. Yet, no studies have examined when delivery-mode differences in adiposity begin to emerge. In this study, we examine differences in infant weight and adiposity trajectories from birth to 12 months by delivery mode.From 2013 to 2015, we recruited pregnant women into the Nurture Study and followed up their 666 infants. We ascertained maternal delivery method and infant birth weight from medical records. We measured weight, length, and skinfold thicknesses (subscapular, triceps, abdominal) when infants were 3, 6, 9, and 12 months of age. The main outcome, infant weight-for-length z score, was derived based on the WHO Child Growth Standards. We used linear regression models to assess the difference at each time point and used linear mixed models to examine the growth rate for infant weight and adiposity trajectories. We controlled for maternal age, race, marital status, education level, household income, smoking status, maternal pre-pregnancy body mass index, and infant birth weight.Of the 563 infants in our final sample, 179 (31.8%) were cesarean delivered. From birth to 12 months, the rate of increase in weight-for-length z score was 0.02/month (p = 0.03) greater for cesarean-delivered than vaginally-delivered infants. As a result of more rapid growth, cesarean-delivered infants had higher weight-for-length z score (0.26, 95% CI: 0.05, 0.47) and sum of subscapular and triceps (SS + TR) skinfold thickness (0.95 mm, 95% CI: 0.30, 1.60)-an indicator for overall adiposity-at 12 months, compared to vaginally-delivered infants.Compared to vaginal delivery, cesarean delivery was associated with greater offspring rate of weight gain over the first year and differences in adiposity that appear as early as 3 months of age. Monitoring cesarean-delivered infants closely for excess weight gain may help guide primordial prevention of obesity later in life.}, number={8}, journal={INTERNATIONAL JOURNAL OF OBESITY}, author={Mueller, Noel T. and Zhang, Mingyu and Hoyo, Cathrine and Ostbye, Truls and Benjamin-Neelon, Sara E.}, year={2019}, month={Aug}, pages={1549–1555} } @article{chawla_fuemmeler_benjamin-neelon_hoyo_murphy_daniels_2019, title={Early prenatal vitamin D concentrations and social-emotional development in infants}, volume={32}, ISSN={["1476-4954"]}, DOI={10.1080/14767058.2017.1408065}, abstractNote={Abstract Background: Many pregnant women in the United States have suboptimal vitamin D, but the impact on infant development is unclear. Moreover, no pregnancy-specific vitamin D recommendations have been widely accepted. Aims: Given the ubiquitous expression of vitamin D receptors in the brain, we investigated the association between early prenatal plasma 25-hydroxyvitamin D (25(OH)D) concentrations and children’s social and emotional development in the Newborn Epigenetic Study, a prospective study of pregnancies from 2009 to 2011 in Durham, North Carolina. Methods: We measured 25(OH)D concentrations in first or second trimester plasma samples and categorized 25(OH)D concentrations into quartiles. Covariates were derived from maternal questionnaires. Mothers completed the Infant Toddler Social-Emotional Development Assessment when children were 12–24 months of age. We used multivariable linear regression to evaluate associations between 25(OH)D and specific behavior scores, adjusted for season of blood draw, maternal age, education, parity, smoking, marital status, prepregnancy BMI, and infant gender. We investigated effect-measure modification by race/ethnicity. Results: Of the 218 mother–infant pairs with complete data, Black mothers had much lower 25(OH)D concentrations as compared to White and Hispanic mothers. After adjustment, lower prenatal 25(OH)D was associated with slightly higher (less favorable) Internalizing scores among White children, but lower (more favorable) Internalizing scores among Black and Hispanic children. Lower prenatal 25(OH)D also appears to be associated with higher (less favorable) dysregulation scores, though only among White and Hispanic children. Conclusions: Though imprecise, preliminary results warrant further investigation regarding a role for prenatal vitamin D on children’s early social and emotional development.}, number={9}, journal={JOURNAL OF MATERNAL-FETAL & NEONATAL MEDICINE}, author={Chawla, Devika and Fuemmeler, Bernard and Benjamin-Neelon, Sara E. and Hoyo, Cathrine and Murphy, Susan and Daniels, Julie L.}, year={2019}, month={May}, pages={1441–1448} } @article{sorrow_maguire_murphy_belcher_hoyo_2019, title={Elevated metabolites of acetaminophen in cord blood of children with obesity}, volume={14}, ISSN={["2047-6302"]}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-85053785805&partnerID=MN8TOARS}, DOI={10.1111/ijpo.12465}, abstractNote={Summary}, number={1}, journal={PEDIATRIC OBESITY}, author={Sorrow, P. and Maguire, R. and Murphy, S. K. and Belcher, S. M. and Hoyo, C.}, year={2019}, month={Jan} } @article{reese_xu_dekker_lee_sikdar_ruiz-arenas_merid_rezwan_page_ullemar_et al._2019, title={Epigenome-wide meta-analysis of DNA methylation and childhood asthma}, volume={143}, ISSN={["1097-6825"]}, DOI={10.1016/j.jaci.2018.11.043}, abstractNote={Epigenetic mechanisms, including methylation, can contribute to childhood asthma. Identifying DNA methylation profiles in asthmatic patients can inform disease pathogenesis.We sought to identify differential DNA methylation in newborns and children related to childhood asthma.Within the Pregnancy And Childhood Epigenetics consortium, we performed epigenome-wide meta-analyses of school-age asthma in relation to CpG methylation (Illumina450K) in blood measured either in newborns, in prospective analyses, or cross-sectionally in school-aged children. We also identified differentially methylated regions.In newborns (8 cohorts, 668 cases), 9 CpGs (and 35 regions) were differentially methylated (epigenome-wide significance, false discovery rate < 0.05) in relation to asthma development. In a cross-sectional meta-analysis of asthma and methylation in children (9 cohorts, 631 cases), we identified 179 CpGs (false discovery rate < 0.05) and 36 differentially methylated regions. In replication studies of methylation in other tissues, most of the 179 CpGs discovered in blood replicated, despite smaller sample sizes, in studies of nasal respiratory epithelium or eosinophils. Pathway analyses highlighted enrichment for asthma-relevant immune processes and overlap in pathways enriched both in newborns and children. Gene expression correlated with methylation at most loci. Functional annotation supports a regulatory effect on gene expression at many asthma-associated CpGs. Several implicated genes are targets for approved or experimental drugs, including IL5RA and KCNH2.Novel loci differentially methylated in newborns represent potential biomarkers of risk of asthma by school age. Cross-sectional associations in children can reflect both risk for and effects of disease. Asthma-related differential methylation in blood in children was substantially replicated in eosinophils and respiratory epithelium.}, number={6}, journal={JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY}, author={Reese, Sarah E. and Xu, Cheng-Jian and Dekker, Herman T. and Lee, Mi Kyeong and Sikdar, Sinjini and Ruiz-Arenas, Carlos and Merid, Simon K. and Rezwan, Faisal I and Page, Christian M. and Ullemar, Vilhelmina and et al.}, year={2019}, month={Jun}, pages={2062–2074} } @article{grant_manichaikul_alberg_bandera_barnholtz-sloan_bondy_cote_funkhouser_moorman_peres_et al._2019, title={Evaluation of vitamin D biosynthesis and pathway target genes reveals UGT2A1/2 and EGFR polymorphisms associated with epithelial ovarian cancer in African American Women}, volume={8}, ISSN={["2045-7634"]}, DOI={10.1002/cam4.1996}, abstractNote={Abstract}, number={5}, journal={CANCER MEDICINE}, author={Grant, Delores J. and Manichaikul, Ani and Alberg, Anthony J. and Bandera, Elisa V and Barnholtz-Sloan, Jill and Bondy, Melissa and Cote, Michele L. and Funkhouser, Ellen and Moorman, Patricia G. and Peres, Lauren C. and et al.}, year={2019}, month={May}, pages={2503–2513} } @article{michael_oyekunle_howard_de hoedt_hoyo_grant_freedland_2019, title={Interplay between exercise and BMI; results from an equal access, racially diverse biopsy study}, volume={30}, ISSN={["1573-7225"]}, DOI={10.1007/s10552-018-1104-2}, abstractNote={{"Label"=>"PURPOSE", "NlmCategory"=>"OBJECTIVE"} It is unclear if exercise and BMI interact to influence prostate cancer (PC) risk. We hypothesized BMI is linked with increased aggressive PC risk but this link will be attenuated with increased exercise. {"Label"=>"METHODS", "NlmCategory"=>"METHODS"} Men undergoing prostate biopsy completed a questionnaire and metabolic equivalent (MET) hours of exercise was calculated. Of 695 men, 349 had PC; 161 low-grade, and 188 high-grade. We assessed the link between exercise and PC risk, high-grade PC (Gleason 7-10), and low-grade PC (Gleason 2-6) using logistic and multinomial logistic regression. Analysis was stratified by BMI. Link between BMI and PC risk and aggressive PC was similarly tested. {"Label"=>"RESULTS", "NlmCategory"=>"RESULTS"} On multivariable analysis, there was no link between exercise and PC diagnosis in the entire cohort (p trend = 0.18-0.71) or across BMI groups (p trend = 0.15-0.97). For the entire cohort, higher BMI was linked with increased risk of high-grade PC (OR 1.06, p = 0.008). When stratified by exercise groups, the trend for higher BMI and increased risk of high-grade PC remained (OR 1.03-1.15, p = 0.02-0.66). There were no interactions between exercise and BMI in predicting PC risk (all p ≥ 0.31). {"Label"=>"CONCLUSIONS", "NlmCategory"=>"CONCLUSIONS"} Regardless of exercise, higher BMI was linked with higher risk of aggressive PC, while exercise was unrelated to PC risk. Confirmatory studies are needed.}, number={1}, journal={CANCER CAUSES & CONTROL}, author={Michael, Jamie and Oyekunle, Taofik and Howard, Lauren and De Hoedt, Amanda and Hoyo, Catherine and Grant, Delores and Freedland, Stephen}, year={2019}, month={Jan}, pages={13–20} } @article{martin_jima_sharp_mccullough_park_gowdy_skaar_cowley_maguire_fuemmeler_et al._2019, title={Maternal pre-pregnancy obesity, offspring cord blood DNA methylation, and offspring cardiometabolic health in early childhood: an epigenome-wide association study}, volume={14}, ISSN={["1559-2308"]}, url={https://doi.org/10.1080/15592294.2019.1581594}, DOI={10.1080/15592294.2019.1581594}, abstractNote={ABSTRACT Pre-pregnancy obesity is an established risk factor for adverse sex-specific cardiometabolic health in offspring. Epigenetic alterations, such as in DNA methylation (DNAm), are a hypothesized link; however, sex-specific epigenomic targets remain unclear. Leveraging data from the Newborn Epigenetics Study (NEST) cohort, linear regression models were used to identify CpG sites in cord blood leukocytes associated with pre-pregnancy obesity in 187 mother-female and 173 mother-male offsprings. DNAm in cord blood was measured using the Illumina HumanMethylation450k BeadChip. Replication analysis was conducted among the Avon Longitudinal Study of Parents and Children (ALSPAC) cohort. Associations between pre-pregnancy obesity-associated CpG sites and offspring BMI z-score (BMIz) and blood pressure (BP) percentiles at 4–5-years of age were also examined. Maternal pre-pregnacy obesity was associated with 876 CpGs in female and 293 CpGs in male offspring (false discovery rate <5%). Among female offspring, 57 CpG sites, including the top 18, mapped to the TAPBP gene (range of effect estimates: −0.83% decrease to 4.02% increase in methylation). CpG methylation differences in the TAPBP gene were also observed among males (range of effect estimates: −0.30% decrease to 2.59% increase in methylation). While technically validated, none of the TAPBP CpG sites were replicated in ALSPAC. In NEST, methylation differences at CpG sites of the TAPBP gene were associated with BMI z-score (cg23922433 and cg17621507) and systolic BP percentile (cg06230948) in female and systolic (cg06230948) and diastolic (cg03780271) BP percentile in male offspring. Together, these findings suggest sex-specific effects, which, if causal, may explain observed sex-specific effects of maternal obesity.}, number={4}, journal={EPIGENETICS}, author={Martin, Chantel L. and Jima, Dereje and Sharp, Gemma C. and McCullough, Lauren E. and Park, Sarah S. and Gowdy, Kymberly M. and Skaar, David and Cowley, Michael and Maguire, Rachel L. and Fuemmeler, Bernard and et al.}, year={2019}, month={Apr}, pages={325–340} } @article{kupers_monnereau_sharp_yousefi_salas_ghantous_page_reese_wilcox_czamara_et al._2019, title={Meta-analysis of epigenome-wide association studies in neonates reveals widespread differential DNA methylation associated with birthweight}, volume={10}, ISSN={["2041-1723"]}, DOI={10.1038/s41467-019-09671-3}, abstractNote={Abstract}, journal={NATURE COMMUNICATIONS}, author={Kupers, Leanne K. and Monnereau, Claire and Sharp, Gemma C. and Yousefi, Paul and Salas, Lucas A. and Ghantous, Akram and Page, Christian M. and Reese, Sarah E. and Wilcox, Allen J. and Czamara, Darina and et al.}, year={2019}, month={Apr} } @article{josey_mccullough_hoyo_williams-devane_2019, title={Overall gestational weight gain mediates the relationship between maternal and child obesity}, volume={19}, ISSN={["1471-2458"]}, DOI={10.1186/s12889-019-7349-1}, abstractNote={Approximately 17% of children in the U.S. are obese. Children that are overweight or obese are also more likely to be obese as adults and suffer from various chronic diseases and premature death. Maternal obesity can affect the weight status of her offspring through intrauterine mechanisms like excessive gestational weight gain (GWG). Current literature shows a positive association between maternal weight status and GWG on child obesity, yet the direct and indirect effects have not been decomposed or quantified. The purpose of this study was to estimate the effect of maternal obesity on child obesity, mediated by GWG, which is a modifiable risk factor.The study participants were a birth cohort of offspring from women who received prenatal care in the Duke/Durham Regional health care system in Durham, NC between 2005 and 2009. Anthropomorphic data was collected via electronic medical records (EMRs) during each voluntary visit to a health care facility. The exposure of interest was maternal obesity, measured by pre-pregnancy body mass index, the mediator was GWG, dichotomized into excessive and not excessive based on maternal prenatal BMI, and the outcome was child obesity at age 4, measured as BMI z-scores from the last recorded height and weight. A counterfactual theory-based product method analysis estimated the mediated effects of GWG, adjusted for maternal race, socioeconomic status, and smoking status.Of the 766 children, 25% were overweight or obese, and among all mothers, 25 and 31% were overweight and obese, respectively. Maternal BMI was associated with an overall increase of 0.04 in offspring z-score. The proportion of the effect of maternal obesity on child age 4 obesity mediated by GWG was 8.1%.GWG, in part, mediated the relationship between maternal BMI and childhood adiposity. Even when the mediator is fixed, children are at an increased risk of a higher BMI if the mother is obese. These findings highlight an important public health education opportunity to stress the impact of a pre-pregnancy weight and excessive GWG on the risk of child obesity for all mothers.}, number={1}, journal={BMC PUBLIC HEALTH}, author={Josey, Michele J. and McCullough, Lauren E. and Hoyo, Cathrine and Williams-DeVane, ClarLynda}, year={2019}, month={Aug} } @article{fuemmeler_zucker_sheng_sanchez_maguire_murphy_kollins_hoyo_2019, title={Pre-Pregnancy Weight and Symptoms of Attention Deficit Hyperactivity Disorder and Executive Functioning Behaviors in Preschool Children}, volume={16}, ISSN={["1660-4601"]}, DOI={10.3390/ijerph16040667}, abstractNote={This study examines pre-pregnancy Body Mass Index (BMI) and gestational weight gain (GWG) in relation to early childhood Attention Deficit Hyperactivity Disorder (ADHD) symptoms and related executive self-regulation behaviors. The analyses sample (n = 331) included a subsample of participants from a birth cohort recruited from prenatal clinics and hospital facilities from April 2005 to June 2011 in Durham, North Carolina. Pre-pregnancy BMI was calculated from weight at the last menstrual period and height was extracted from medical records. Gestational weight gain was calculated from pre-pregnancy weight and weight measured at the time of delivery. ADHD symptoms and executive self-regulation behaviors were assessed by maternal report (mean age = 3 years). Multivariable regression methods with inverse probability weighting (IPW) were used to evaluate associations accounting for sample selection bias and confounding. Pre-pregnancy BMI at levels ≥35 was positively associated with higher ADHD symptoms and worse executive self-regulation behaviors (inhibitory control and attention). Compared to adequate GWG, less than adequate GWG was related to more ADHD hyperactive-impulsive symptoms, whereas greater than adequate GWG was related to more problematic behaviors related to working memory and planning. The findings support a link between maternal weight and child neurodevelopment. Continued research that help identify biological mechanisms are needed.}, number={4}, journal={INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH}, author={Fuemmeler, Bernard F. and Zucker, Nancy and Sheng, Yaou and Sanchez, Carmen E. and Maguire, Rachel and Murphy, Susan K. and Kollins, Scott H. and Hoyo, Cathrine}, year={2019}, month={Feb} } @article{skinner_lumey_fleming_sapienza_hoyo_aronica_thompson_nichol_2019, title={RW-2018-Research Workshop: The Effect of Nutrition on Epigenetic Status, Growth, and Health}, volume={43}, ISSN={["1941-2444"]}, DOI={10.1002/jpen.1536}, abstractNote={Abstract}, number={5}, journal={JOURNAL OF PARENTERAL AND ENTERAL NUTRITION}, author={Skinner, Michael and Lumey, L. H. and Fleming, Tom P. and Sapienza, Carmen and Hoyo, Cathrine and Aronica, Lucia and Thompson, Jeff and Nichol, Peter F.}, year={2019}, month={Jul}, pages={627–637} } @article{chawla_daniels_benjamin-neelon_fuemmeler_hoyo_buckley_2019, title={Racial and ethnic differences in predictors of vitamin D among pregnant women in south-eastern USA}, volume={8}, ISSN={["2048-6790"]}, DOI={10.1017/jns.2019.4}, abstractNote={Abstract}, journal={JOURNAL OF NUTRITIONAL SCIENCE}, author={Chawla, Devika and Daniels, Julie L. and Benjamin-Neelon, Sara E. and Fuemmeler, Bernard F. and Hoyo, Cathrine and Buckley, Jessie P.}, year={2019}, month={Feb} } @article{bergens_pittman_thompson_campbell_wang_hoyo_bell_2019, title={Smoking-associated AHRR demethylation in cord blood DNA: impact of CD235a+nucleated red blood cells}, volume={11}, ISSN={["1868-7083"]}, DOI={10.1186/s13148-019-0686-1}, abstractNote={Numerous studies have demonstrated that DNA methylation levels in the aryl hydrocarbon receptor repressor (AHRR) gene measured in cord blood are significantly associated with prenatal tobacco smoke exposure and can be used as a fetal exposure biomarker. The mechanism driving this demethylation has not been determined and it is unclear if all cord blood cell types are impacted. Nucleated red blood cells (nRBCs/CD235a+ cells) are developmentally immature RBCs that display genome-wide hypomethylation and are observed at increased frequency in the cord blood of smoking mothers. We tested if AHRR methylation levels in CD235a+ nRBCs or nRBC counts influenced AHRR methylation in whole cord blood.Cord blood was collected from smoking (n = 34) and nonsmoking (n = 19) mothers and DNA was prepared from whole cord blood, isolated CD235a+ nRBCs, and CD14+ monocytes. AHRR methylation in cord blood DNA was measured using Illumina 850K arrays (cg05575921, chr5:373378). Pyrosequencing was used to compare methylation levels among cord blood, CD235a+, and CD14+ cells. We measured nRBC percentages using conventional complete blood counts and estimated percent nRBCs by a deconvolution model.Methylation levels in AHRR were significantly lower in nRBCs relative to whole cord blood and CD14+ monocytes. While AHRR methylation levels in the cell types were significantly correlated across all subjects, methylation values at the chr5:373378 CpG averaged 14.6% lower in nRBCs (range 0.4 to 24.8%; p = 3.8E-13) relative to CD14+, with nonsmokers showing a significantly greater hypomethylation (- 4.1%, p = 1.8E-02). Methylation level at the AHRR chr5:373378 CpG was strongly associated with self-reported smoking in both CD14+ monocytes (t test p = 5.7E-09) and nRBCs (p = 4.8E-08), as well as cotinine levels (regression p = 1.1E-07 and p = 3.6E-04, respectively). For subjects with whole blood 850K data, robust linear regression models adjusting for estimated cell type composition, either including nRBCs counts or estimates, modestly increased the association between smoking and cg05575921 methylation.Prenatal smoke exposure was highly significantly associated with AHRR methylation in cord blood, CD14+ monocytes, and CD235a+ nRBCs. AHRR methylation levels in nRBCs and nRBC counts had minimal effect on cord blood methylation measurements. However, regression models using estimated nRBCs or actual nRBC counts outperformed those lacking these covariates.}, journal={CLINICAL EPIGENETICS}, author={Bergens, Matthew A. and Pittman, Gary S. and Thompson, Isabel J. B. and Campbell, Michelle R. and Wang, Xuting and Hoyo, Cathrine and Bell, Douglas A.}, year={2019}, month={Jun} } @article{xue_maguire_liu_kollins_murphy_hoyo_fuemmeler_2019, title={Snacking frequency and dietary intake in toddlers and preschool children}, volume={142}, ISSN={["1095-8304"]}, DOI={10.1016/j.appet.2019.104369}, abstractNote={Understanding the relationship between snacking and dietary intake in early life years is one key but understudied area. In this study, we examined snacking patterns in toddlers and preschool children and the associations between snacking frequency and daily energy intake. We analyzed data from children aged 12–72 months (N = 1186) in the Newborn Epigenetic STudy (NEST). We used Bonferroni multiple comparison methods to examine the differences in snacking patterns across subgroups. Linear and quantile regression models were fit to investigate the association between dietary intake and snacking frequency. Our estimates suggest that Non-Hispanic blacks had the highest total daily energy intake from snacks (334 kcal/day) compared to non-Hispanic whites (270 kcal/day) and Hispanics (274 kcal/day) in 12-to-24-month-olds. In 2-to-6-year-olds, mean energy intake from snacks was 296 kcal/day without a significant racial/ethnic difference. Carbohydrate, fat and protein from snacks contributed about 17%, 9% and 4% respectively of the total energy intake in 12-to-24-month-olds while they contributed about 15%, 7% and 2% respectively of the total energy intake in the other age group. Snacking frequency was positively and significantly associated with total daily energy intake in both 12-to-24-month-olds and 2-to-6-year-olds as indicated by regression coefficient estimates of snacking frequency (β = 31.3 kcal/day with P = 0.027 and β = 175.4 kcal/day with P < 0.0001, respectively, indicating a higher snacking frequency was associated with a greater total daily energy intake). In conclusion, snacking frequency was positively associated with daily energy intake. Carbohydrates and fats from snacks are significant energy contributors. Age differentiation was apparent regarding the relationship between snacking frequency and dietary intake. Differentiated interventions that are age-specific and focus on the dietary quality of snacks instead of quantity are needed.}, journal={APPETITE}, author={Xue, Hong and Maguire, Rachel L. and Liu, Jin and Kollins, Scott H. and Murphy, Susan K. and Hoyo, Cathrine and Fuemmeler, Bernard F.}, year={2019}, month={Nov} } @article{dozmorov_bilbo_kollins_zucker_do_schechter_zhang_murphy_hoyo_fuemmeler_2018, title={Associations between maternal cytokine levels during gestation and measures of child cognitive abilities and executive functioning}, volume={70}, ISSN={["1090-2139"]}, DOI={10.1016/j.bbi.2018.03.029}, abstractNote={Preclinical studies demonstrate that environmentally-induced alterations in inflammatory cytokines generated by the maternal and fetal immune system can significantly impact fetal brain development. Yet, the relationship between maternal cytokines during gestation and later cognitive ability and executive function remains understudied. Children (n = 246) were born of mothers enrolled in the Newborn Epigenetic Study – a prospective pre-birth cohort in the Southeastern US. We characterized seven cytokines [IL-1β, IL-4,IL-6, IL-12p70, IL-17A, tumor necrosis factor-α (TNFα), and interferon-γ (IFNγ)] and one chemokine (IL-8) from maternal plasma collected during pregnancy. We assessed children’s cognitive abilities and executive functioning at a mean age of 4.5 (SD = 1.1) years. Children’s DAS-II and NIH toolbox scores were regressed on cytokines and the chemokine, controlling for maternal age, race, education, body mass index, IQ, parity, smoking status, delivery type, gestational weeks, and child birth weight and sex. Higher IL-12p70 (βIL-12p70 = 4.26, p = 0.023) and IL-17A (βIL-17A = 3.70, p = 0.042) levels were related to higher DAS-II GCA score, whereas higher IL-1β (βIL-1B = −6.07, p = 0.003) was related to lower GCA score. Higher IL-12p70 was related to higher performance on NIH toolbox measures of executive functions related to inhibitory control and attention (βIL-12p70 = 5.20, p = 0.046) and cognitive flexibility (βIL-12p70 = 5.10, p = 0.047). Results suggest that dysregulation in gestational immune activity are associated with child cognitive ability and executive functioning.}, journal={BRAIN BEHAVIOR AND IMMUNITY}, author={Dozmorov, Mikhail G. and Bilbo, Staci D. and Kollins, Scott H. and Zucker, Nancy and Do, Elizabeth K. and Schechter, Julia C. and Zhang, Junfeng and Murphy, Susan K. and Hoyo, Cathrine and Fuemmeler, Bernard F.}, year={2018}, month={May}, pages={390–397} } @article{green_hoyo_mattingly_luo_tzeng_murphy_buchwalter_planchart_2018, title={Cadmium exposure increases the risk of juvenile obesity: a human and zebrafish comparative study}, volume={42}, ISSN={0307-0565 1476-5497}, url={http://dx.doi.org/10.1038/S41366-018-0036-Y}, DOI={10.1038/S41366-018-0036-Y}, abstractNote={Human obesity is a complex metabolic disorder disproportionately affecting people of lower socioeconomic strata, and ethnic minorities, especially African Americans and Hispanics. Although genetic predisposition and a positive energy balance are implicated in obesity, these factors alone do not account for the excess prevalence of obesity in lower socioeconomic populations. Therefore, environmental factors, including exposure to pesticides, heavy metals, and other contaminants, are agents widely suspected to have obesogenic activity, and they also are spatially correlated with lower socioeconomic status. Our study investigates the causal relationship between exposure to the heavy metal, cadmium (Cd), and obesity in a cohort of children and in a zebrafish model of adipogenesis.An extensive collection of first trimester maternal blood samples obtained as part of the Newborn Epigenetics Study (NEST) was analyzed for the presence of Cd, and these results were cross analyzed with the weight-gain trajectory of the children through age 5 years. Next, the role of Cd as a potential obesogen was analyzed in an in vivo zebrafish model.Our analysis indicates that the presence of Cd in maternal blood during pregnancy is associated with increased risk of juvenile obesity in the offspring, independent of other variables, including lead (Pb) and smoking status. Our results are recapitulated in a zebrafish model, in which exposure to Cd at levels approximating those observed in the NEST study is associated with increased adiposity.Our findings identify Cd as a potential human obesogen. Moreover, these observations are recapitulated in a zebrafish model, suggesting that the underlying mechanisms may be evolutionarily conserved, and that zebrafish may be a valuable model for uncovering pathways leading to Cd-mediated obesity in human populations.}, number={7}, journal={International Journal of Obesity}, publisher={Springer Science and Business Media LLC}, author={Green, Adrian J. and Hoyo, Cathrine and Mattingly, Carolyn J. and Luo, Yiwen and Tzeng, Jung-Ying and Murphy, Susan K. and Buchwalter, David B. and Planchart, Antonio}, year={2018}, month={Feb}, pages={1285–1295} } @article{felix_joubert_baccarelli_sharp_almqvist_annesi-maesano_arshad_baiz_bakermans-kranenburg_bakulski_et al._2018, title={Cohort profile: Pregnancy and childhood epigenetics (PACE) consortium}, volume={47}, number={1}, journal={International Journal of Epidemiology}, author={Felix, J. F. and Joubert, B. R. and Baccarelli, A. A. and Sharp, G. C. and Almqvist, C. and Annesi-Maesano, I. and Arshad, H. and Baiz, N. and Bakermans-Kranenburg, M. J. and Bakulski, K. M. and et al.}, year={2018}, pages={22-} } @article{gomih_smith_north_hudgens_brewster_huang_skaar_valea_bentley_vidal_et al._2018, title={DNA methylation of imprinted gene control regions in the regression of low-grade cervical lesions}, volume={143}, ISSN={["1097-0215"]}, DOI={10.1002/ijc.31350}, abstractNote={The role of host epigenetic mechanisms in the natural history of low‐grade cervical intraepithelial neoplasia (CIN1) is not well characterized. We explored differential methylation of imprinted gene regulatory regions as predictors of the risk of CIN1 regression. A total of 164 patients with CIN1 were recruited from 10 Duke University clinics for the CIN Cohort Study. Participants had colposcopies at enrollment and up to five follow‐up visits over 3 years. DNA was extracted from exfoliated cervical cells for methylation quantitation at CpG (cytosine‐phosphate‐guanine) sites and human papillomavirus (HPV) genotyping. Hazard ratios (HR) and 95% confidence intervals (CI) were estimated using Cox regression to quantify the effect of methylation on CIN1 regression over two consecutive visits, compared to non‐regression (persistent CIN1; progression to CIN2+; or CIN1 regression at a single time‐point), adjusting for age, race, high‐risk HPV (hrHPV), parity, oral contraceptive and smoking status. Median participant age was 26.6 years (range: 21.0–64.4 years), 39% were African‐American, and 11% were current smokers. Most participants were hrHPV‐positive at enrollment (80.5%). Over one‐third of cases regressed (n = 53, 35.1%). Median time‐to‐regression was 12.6 months (range: 4.5–24.0 months). Probability of CIN1 regression was negatively correlated with methylation at IGF2AS CpG 5 (HR = 0.41; 95% CI = 0.23–0.77) and PEG10 DMR (HR = 0.80; 95% CI = 0.65–0.98). Altered methylation of imprinted IGF2AS and PEG10 DMRs may play a role in the natural history of CIN1. If confirmed in larger studies, further research on imprinted gene DMR methylation is warranted to determine its efficacy as a biomarker for cervical cancer screening.}, number={3}, journal={INTERNATIONAL JOURNAL OF CANCER}, author={Gomih, Ayodele and Smith, Jennifer S. and North, Kari E. and Hudgens, Michael G. and Brewster, Wendy R. and Huang, Zhiqing and Skaar, David and Valea, Fidel and Bentley, Rex C. and Vidal, Adriana C. and et al.}, year={2018}, month={Aug}, pages={552–560} } @article{gonzalez-nahm_mendez_benjamin-neelon_murphy_hogan_rowley_hoyo_2018, title={DNA methylation of imprinted genes at birth is associated with child weight status at birth, 1 year, and 3 years}, volume={10}, journal={Clinical Epigenetics}, author={Gonzalez-Nahm, S. and Mendez, M. A. and Benjamin-Neelon, S. E. and Murphy, S. K. and Hogan, V. K. and Rowley, D. L. and Hoyo, C.}, year={2018} } @article{hoyo_skaar_park_sorrow_2018, title={EPIGENOMICS AND HUMAN OBESITY}, volume={6}, ISBN={["978-0-12-812215-0"]}, DOI={10.1016/B978-0-12-812215-0.00014-5}, abstractNote={Obesity has become one of the most urgent public health problems globally with the steepest increases in prevalence reported among socioeconomically disadvantaged and ethnic minorities. Obesity is associated with sizable reductions in life expectancy and quality of life. Although evidence from model systems supports that epigenetic dysregulation may cause obesity, the affected pathways are still unclear. This chapter summarizes human data on CpG methylation, the most studied epigenetic mechanism in humans, in the context of causal inference, in adults and children. Recent technological advances in the measurement of CpG methylation have led to the identification of multiple obesity-related sequence regions. Still limited are data on the temporal stability of regions identified thus far, and the extent to which obesity-related sequence regions remain significant in ethnic minorities. We conclude with a call for sex- and ethnic-specific data, together with data demonstrating that obesity-associated DNA methylation marks identified precede obesity.}, journal={EPIGENETICS IN HUMAN DISEASE, 2ND EDITION}, author={Hoyo, Cathrine and Skaar, David A. and Park, Sarah S. and Sorrow, Patricia}, year={2018}, pages={409–426} } @article{cowley_skaar_jima_maguire_hudson_park_sorrow_hoyo_2018, title={Effects of cadmium exposure on DNA methylation at imprinting control regions and genome-wide in mothers and newborn children}, volume={126}, number={3}, journal={Environmental Health Perspectives}, author={Cowley, M. and Skaar, D. A. and Jima, D. D. and Maguire, R. L. and Hudson, K. M. and Park, S. S. and Sorrow, P. and Hoyo, C.}, year={2018} } @article{planchart_green_hoyo_mattingly_2018, title={Heavy Metal Exposure and Metabolic Syndrome: Evidence from Human and Model System Studies}, volume={5}, ISSN={2196-5412}, url={http://dx.doi.org/10.1007/S40572-018-0182-3}, DOI={10.1007/S40572-018-0182-3}, abstractNote={Metabolic syndrome (MS) describes the co-occurrence of conditions that increase one’s risk for heart disease and other disorders such as diabetes and stroke. The worldwide increase in the prevalence of MS cannot be fully explained by lifestyle factors such as sedentary behavior and caloric intake alone. Environmental exposures, such as heavy metals, have been implicated, but results are conflicting and possible mechanisms remain unclear. To assess recent progress in determining a possible role between heavy metal exposure and MS, we reviewed epidemiological and model system data for cadmium (Cd), lead (Pb), and mercury (Hg) from the last decade. Data from 36 epidemiological studies involving 17 unique countries/regions and 13 studies leveraging model systems are included in this review. Epidemiological and model system studies support a possible association between heavy metal exposure and MS or comorbid conditions; however, results remain conflicting. Epidemiological studies were predominantly cross-sectional and collectively, they highlight a global interest in this question and reveal evidence of differential susceptibility by sex and age to heavy metal exposures. In vivo studies in rats and mice and in vitro cell-based assays provide insights into potential mechanisms of action relevant to MS including altered regulation of lipid and glucose homeostasis, adipogenesis, and oxidative stress. Heavy metal exposure may contribute to MS or comorbid conditions; however, available data are conflicting. Causal inference remains challenging as epidemiological data are largely cross-sectional; and variation in study design, including samples used for heavy metal measurements, age of subjects at which MS outcomes are measured; the scope and treatment of confounding factors; and the population demographics vary widely. Prospective studies, standardization or increased consistency across study designs and reporting, and consideration of molecular mechanisms informed by model system studies are needed to better assess potential causal links between heavy metal exposure and MS.}, number={1}, journal={Current Environmental Health Reports}, publisher={Springer Science and Business Media LLC}, author={Planchart, Antonio and Green, Adrian and Hoyo, Cathrine and Mattingly, Carolyn J.}, year={2018}, month={Feb}, pages={110–124} } @article{schechter_fuemmeler_hoyo_murphy_zhang_kollins_2018, title={Impact of smoking ban on passive smoke exposure in pregnant non-smokers in the Southeastern United States}, volume={15}, number={1}, journal={International Journal of Environmental Research and Public Health}, author={Schechter, J. C. and Fuemmeler, B. F. and Hoyo, C. and Murphy, S. K. and Zhang, J. F. and Kollins, S. H.}, year={2018} } @article{neelon_white_vidal_schildkraut_murtha_murphy_kullman_hoyo_2018, title={Maternal vitamin D, DNA methylation at imprint regulatory regions and offspring weight at birth, 1 year and 3 years}, volume={42}, ISSN={["1476-5497"]}, DOI={10.1038/ijo.2017.160}, abstractNote={Vitamin D deficiency during pregnancy is associated with poor birth outcomes in some studies, but few have examined weight beyond birth. In addition, little is known about how vitamin D influences DNA methylation of regulatory regions known to be involved in growth, as possible mediators to weight status in offspring. We conducted linear regressions to assess maternal plasma 25-hydroxyvitamin D (25(OH)D) by quartile and birth weight for gestational age z-score, 1-year weight-for-length z-score and 3-year body mass index (BMI) z-score among 476 mother/infant dyads from a prospective cohort. We assessed maternal 25(OH)D and infant DNA methylation at nine differentially methylated regions (DMRs) of genomically imprinted genes with known functions in fetal growth, including H19, IGF2, MEG3, MEG3-IG, MEST, NNAT, PEG3, PLAGL1 and SGCE/PEG10. Mean (standard deviation, s.d.) maternal 25(OH)D was 41.1 (14.2) nmol l−m at a mean (s.d.) of 13.2 (5.5) weeks gestation. After adjustment for potential confounders, the first (Q1) and second (Q2) quartiles of 25(OH)D, compared to the fourth (Q4), were associated with lower birth weight for gestational age z-scores (−0.43 units; CI: −0.79, −0.07; P=0.02 for Q1 and −0.56 units; CI: −0.89, −0.23; P=0.001 for Q2). Q1 compared to Q4 was associated with higher 1-year weight-for-length z-scores (0.78 units; 0.08, 1.54; P=0.04) and higher 3-year BMI z-scores (0.83 units; 0.11, 0.93; P=0.02). We did not observe associations between maternal 25(OH)D and methylation for any of the nine DMRs after correcting for multiple testing. Reduced maternal 25(OH)D was associated with lower birth weight for gestational age z-scores but higher 1-year weight-for-length and 3-year BMI z-scores in offspring. However, 25(OH)D does not appear to be operating through the regulatory sequences of the genomically imprinted genes we examined.}, number={4}, journal={INTERNATIONAL JOURNAL OF OBESITY}, author={Neelon, S. E. Benjamin and White, A. J. and Vidal, A. C. and Schildkraut, J. M. and Murtha, A. P. and Murphy, S. K. and Kullman, S. W. and Hoyo, C.}, year={2018}, month={Apr}, pages={587–593} } @article{house_mendez_maguire_gonzalez-nahm_huang_daniels_murphy_fuemmeler_wright_hoyo_2018, title={Periconceptional maternal mediterranean diet is associated with favorable offspring behaviors and altered CpG methylation of imprinted genes}, volume={6}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-85053720031&partnerID=MN8TOARS}, DOI={10.3389/fcell.2018.00107}, abstractNote={Background: Maternal diet during pregnancy has been shown to influence the child neuro-developmental outcomes. Studies examining effects of dietary patterns on offspring behavior are sparse. Objective: Determine if maternal adherence to a Mediterranean diet is associated with child behavioral outcomes assessed early in life, and to evaluate the role of differentially methylated regions (DMRs) regulating genomically imprinted genes in these associations. Methods: Among 325 mother/infant pairs, we used regression models to evaluate the association between tertiles of maternal periconceptional Mediterranean diet adherence (MDA) scores derived from a Food Frequency Questionnaire, and social and emotional scores derived from the Infant Toddler Social and Emotional Assessment (ITSEA) questionnaire in the second year of life. Methylation of nine genomically imprinted genes was measured to determine if MDA was associated with CpG methylation. Results: Child depression was inversely associated with maternal MDA (Bonferroni-corrected p = 0.041). While controlling for false-discovery, compared to offspring of women with the lowest MDA tertile, those with MDA scores in middle and high MDA tertiles had decreased odds for atypical behaviors [OR (95% CI) = 0.40 (0.20, 0.78) for middle and 0.40 (0.17, 0.92) for highest tertile], for maladaptive behaviors [0.37 (0.18, 0.72) for middle tertile and 0.42 (0.18, 0.95) for highest tertile] and for an index of autism spectrum disorder behaviors [0.46 (0.23, 0.90) for middle and 0.35 (0.15, 0.80) for highest tertile]. Offspring of women with the highest MDA tertile were less likely to exhibit depressive [OR = 0.28 (0.12, 0.64)] and anxiety [0.42 (0.18, 0.97)] behaviors and increased odds of social relatedness [2.31 (1.04, 5.19)] behaviors when compared to low MDA mothers. Some associations varied by sex. Perinatal MDA score was associated with methylation differences for imprinted control regions of PEG10/SGCE [females: Beta (95% CI) = 1.66 (0.52, 2.80) – Bonferroni-corrected p = 0.048; males: -0.56 (-1.13, -0.00)], as well as both MEG3 and IGF2 in males [0.97 (0.00, 1.94)] and -0.92 (-1.65, -0.19) respectively. Conclusion: In this ethnically diverse cohort, maternal adherence to a Mediterranean diet in early pregnancy was associated with favorable neurobehavioral outcomes in early childhood and with sex-dependent methylation differences of MEG3, IGF2, and SGCE/PEG10 DMRs.}, number={SEP}, journal={Frontiers in Cell and Developmental Biology}, author={House, John S. and Mendez, M. and Maguire, R.L. and Gonzalez-Nahm, S. and Huang, Z. and Daniels, J. and Murphy, S.K. and Fuemmeler, B.F. and Wright, F.A. and Hoyo, C.}, year={2018}, pages={107} } @article{golden_yu_meilleur_blakeley_duff_karton_vrielink_2017, title={An Extended n-h bond, driven by a conserved second-order interaction, orients the flavin n5 orbital in cholesterol oxidase}, volume={7}, journal={Scientific Reports}, author={Golden, E. and Yu, L. J. and Meilleur, F. and Blakeley, M. P. and Duff, A. P. and Karton, A. and Vrielink, A.}, year={2017} } @article{neelon_ostbye_bennett_kravitz_clancy_stroo_iversen_hoyo_2017, title={Cohort profile for the Nurture Observational Study examining associations of multiple caregivers on infant growth in the Southeastern USA}, volume={7}, number={2}, journal={BMJ Open}, author={Neelon, S. E. B. and Ostbye, T. and Bennett, G. G. and Kravitz, R. M. and Clancy, S. M. and Stroo, M. and Iversen, E. and Hoyo, C.}, year={2017} } @article{maguire_vidal_murphy_hoyo_2017, title={Disparities in cervical cancer incidence and mortality: Can epigenetics contribute to eliminating disparities?}, volume={133}, journal={Cancer disparities}, author={Maguire, R. L. and Vidal, A. C. and Murphy, S. K. and Hoyo, C.}, year={2017}, pages={129–156} } @article{gao_millstein_siegmund_dubeau_maguire_gilliland_murphy_hoyo_breton_2017, title={Epigenetic regulation of AXL and risk of childhood asthma symptoms}, volume={9}, journal={Clinical Epigenetics}, author={Gao, L. and Millstein, J. and Siegmund, K. D. and Dubeau, L. and Maguire, R. and Gilliland, F. D. and Murphy, S. K. and Hoyo, C. and Breton, C. V.}, year={2017} } @article{guerrios-rivera_howard_frank_de hoedt_beverly_grant_hoyo_freedland_2017, title={Is Body Mass Index the Best Adiposity Measure for Prostate Cancer Risk? Results From a Veterans Affairs Biopsy Cohort}, volume={105}, ISSN={["1527-9995"]}, DOI={10.1016/j.urology.2017.03.042}, abstractNote={To test multiple adiposity measures and prostate cancer (PC) risk in men undergoing prostate biopsy. We hypothesized that body mass index (BMI), body fat, and waist circumference would be highly correlated, and all would be associated with aggressive PC, but not overall risk.A case (483)-control (496) study among men undergoing prostate biopsy from 2007 to 2016 was conducted at the Durham Veterans Affairs Medical Center. Anthropometric and self-reported measurements were taken. Percent body fat was measured. Associations between adiposity measures and PC risk and high-grade PC (Gleason ≥7) were examined using logistic regression.BMI, percent body fat, and waist circumference were highly correlated (ρ ≥ .79) (P < .001). On multivariable analysis, BMI (P = .011) was associated with overall PC risk, but percent body fat (P = .16) and waist circumference (P = .19) were not. However, all adiposity measurements were associated with high-grade disease (P < .001). We found a strong relationship between self-reported and measured weight (ρ = .97) and height (ρ = .92).BMI, body fat, and waist circumference were all highly correlated and associated with aggressive PC. This study supports the idea that higher adiposity is selectively associated with high-grade PC and reinforces the continued use of self-reported BMI as a measure of obesity in epidemiologic studies of PC.}, journal={UROLOGY}, author={Guerrios-Rivera, Lourdes and Howard, Lauren and Frank, Jennifer and De Hoedt, Amanda and Beverly, Devon and Grant, Delores J. and Hoyo, Cathrine and Freedland, Stephen J.}, year={2017}, month={Jul}, pages={129–135} } @article{freedland_hoyo_turner_moorman_muller_faria_carvahal_reis_mauad_carvalho_et al._2017, title={MP92-09 Implications of Regionalizing Care in the Developing World: Impact of Distance to Referral Center on Compliance to Biopsy Recommendations in a Brazilian Prostate Cancer Screening Cohort}, volume={197}, ISSN={0022-5347 1527-3792}, url={http://dx.doi.org/10.1016/J.JURO.2017.02.2870}, DOI={10.1016/J.JURO.2017.02.2870}, abstractNote={You have accessJournal of UrologyGeneral & Epidemiological Trends & Socioeconomics: Quality Improvement & Patient Safety II1 Apr 2017MP92-09 IMPLICATIONS OF REGIONALIZING CARE IN THE DEVELOPING WORLD: IMPACT OF DISTANCE TO REFERRAL CENTER ON COMPLIANCE TO BIOPSY RECOMMENDATIONS IN A BRAZILIAN PROSTATE CANCER SCREENING COHORT Alexis Freedland, Cathrine Hoyo, Elizabeth Turner, Patricia Moorman, Roberto Muller, Eliney Faria, Gustavo Carvahal, Rodolfo Reis, Edmundo Mauad, Andre Carvalho, and Stephen Freedland Alexis FreedlandAlexis Freedland More articles by this author , Cathrine HoyoCathrine Hoyo More articles by this author , Elizabeth TurnerElizabeth Turner More articles by this author , Patricia MoormanPatricia Moorman More articles by this author , Roberto MullerRoberto Muller More articles by this author , Eliney FariaEliney Faria More articles by this author , Gustavo CarvahalGustavo Carvahal More articles by this author , Rodolfo ReisRodolfo Reis More articles by this author , Edmundo MauadEdmundo Mauad More articles by this author , Andre CarvalhoAndre Carvalho More articles by this author , and Stephen FreedlandStephen Freedland More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2017.02.2870AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES In many developing countries, care is regionalized at a few high volume centers. However, unlike Western nations where high percentages live in urban areas, developing countries have a higher percent living in rural areas or small towns. It is unknown if the benefits of regionalization outweigh the barriers this creates for access. We tested the link between distance from screening site to biopsy (bx) referral center and risk of non-compliance with showing up to have a bx in a population-based PC screening cohort in Brazil. METHODS We reviewed records from 1,561 men recommended to undergo a bx after an initial PC screen by a medical mobile unit at their local clinic between 2004 and 2007. Bxs were performed at a regional referral center, Barretos Cancer Hospital (BCH). Clinical data between men who complied with the bx vs. not were compared with rank-sum & chi-square. Multivariable logistic regression analysis of distance from screening site to BCH (km) and risk of non-compliance was performed adjusting for age and year of screening. RESULTS Median distance was 257km (IQR 135-718). Non-compliant men were older (68 vs 66 yrs), had a higher PSA (4.9 vs 4.2), were less likely to have an abnormal DRE (20% vs 33%) and lived further from BCH (921 vs 225 km) (all p<0.001). On crude and multivariable analyses, further distance was significantly linked with bx non-compliance (OR/100km 0.83, p<0.001, see figure). Among men who lived within 150km of BCH, distance was unrelated to compliance (OR/100km 1.09, p=0.87). CONCLUSIONS In Brazil, where distances from PC screening to bx clinic can be hundreds of kms, greater distance to referral center was related to reduced compliance to bx. However, among men who lived within 150km, distance was unrelated to compliance. While regionalization of care may in theory improve quality, it comes at the cost of reduced compliance and thus reduced access and represents a significant barrier to optimal care if distances are large. In regards to PC screening and bx, our data suggest distances up to 150km do not create barriers for care. Alternative thresholds, however, may apply for other services and in other cultures. © 2017FiguresReferencesRelatedDetails Volume 197Issue 4SApril 2017Page: e1229-e1230 Advertisement Copyright & Permissions© 2017MetricsAuthor Information Alexis Freedland More articles by this author Cathrine Hoyo More articles by this author Elizabeth Turner More articles by this author Patricia Moorman More articles by this author Roberto Muller More articles by this author Eliney Faria More articles by this author Gustavo Carvahal More articles by this author Rodolfo Reis More articles by this author Edmundo Mauad More articles by this author Andre Carvalho More articles by this author Stephen Freedland More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...}, number={4S}, journal={Journal of Urology}, publisher={Ovid Technologies (Wolters Kluwer Health)}, author={Freedland, Alexis and Hoyo, Cathrine and Turner, Elizabeth and Moorman, Patricia and Muller, Roberto and Faria, Eliney and Carvahal, Gustavo and Reis, Rodolfo and Mauad, Edmundo and Carvalho, Andre and et al.}, year={2017}, month={Apr} } @article{sharp_salas_monnereau_allard_yousefi_everson_bohlin_xu_huang_reese_et al._2017, title={Maternal BMI at the start of pregnancy and offspring epigenome-wide DNA methylation: findings from the pregnancy and childhood epigenetics (PACE) consortium}, volume={26}, number={20}, journal={Human Molecular Genetics}, author={Sharp, G. C. and Salas, L. A. and Monnereau, C. and Allard, C. and Yousefi, P. and Everson, T. M. and Bohlin, J. and Xu, Z. L. and Huang, R. C. and Reese, S. E. and et al.}, year={2017}, pages={4067–4085} } @article{luo_mccullough_tzeng_darrah_vengosh_maguire_maity_samuel-hodge_murphy_mendez_et al._2017, title={Maternal blood cadmium, lead and arsenic levels, nutrient combinations, and offspring birthweight}, volume={17}, journal={BMC Public Health}, author={Luo, Y. W. and McCullough, L. E. and Tzeng, J. Y. and Darrah, T. and Vengosh, A. and Maguire, R. L. and Maity, A. and Samuel-Hodge, C. and Murphy, S. K. and Mendez, M. A. and et al.}, year={2017} } @article{mccullough_miller_calderwood_shivappa_steck_forman_mendez_maguire_fuemmeler_kollins_et al._2017, title={Maternal inflammatory diet and adverse pregnancy outcomes: Circulating cytokines and genomic imprinting as potential regulators?}, volume={12}, ISSN={["1559-2308"]}, DOI={10.1080/15592294.2017.1347241}, abstractNote={ABSTRACT Excessive inflammation during pregnancy alters homeostatic mechanisms of the developing fetus and has been linked to adverse pregnancy outcomes. An anti-inflammatory diet could be a promising avenue to combat the pro-inflammatory state of pregnancy, particularly in obese women, but we lack mechanistic data linking this dietary pattern during pregnancy to inflammation and birth outcomes. In an ethnically diverse cohort of 1057 mother-child pairs, we estimated the relationships between dietary inflammatory potential [measured via the energy-adjusted dietary inflammatory index (E-DII™)] and birth outcomes overall, as well as by offspring sex and maternal pre-pregnancy body mass index (BMI). In a subset of women, we also explored associations between E-DII, circulating cytokines (n = 105), and offspring methylation (n = 338) as potential modulators of these relationships using linear regression. Adjusted regression models revealed that women with pro-inflammatory diets had elevated rates of preterm birth among female offspring [β = −0.22, standard error (SE) = 0.07, P<0.01], but not male offspring (β=0.09, SE = 0.06, P<0.12) (Pinteraction = 0.003). Similarly, we observed pro-inflammatory diets were associated with higher rates of caesarean delivery among obese women (β = 0.17, SE = 0.08, P = 0.03), but not among women with BMI <25 kg/m2 (Pinteraction = 0.02). We observed consistent inverse associations between maternal inflammatory cytokine concentrations (IL-12, IL-17, IL-4, IL-6, and TNFα) and lower methylation at the MEG3 regulatory sequence (P<0.05); however, results did not support the link between maternal E-DII and circulating cytokines. We replicate work by others on the association between maternal inflammatory diet and adverse pregnancy outcomes and provide the first empirical evidence supporting the inverse association between circulating cytokine concentrations and offspring methylation.}, number={8}, journal={EPIGENETICS}, author={McCullough, Lauren E. and Miller, Erline E. and Calderwood, Laura E. and Shivappa, Nitin and Steck, Susan E. and Forman, Michele R. and Mendez, Michelle A. and Maguire, Rachel and Fuemmeler, Bernard F. and Kollins, Scott H. and et al.}, year={2017}, pages={688–697} } @article{hoffman_butt_webster_preston_hammel_makey_lorenzo_cooper_carignan_meeker_et al._2017, title={Temporal Trends in Exposure to Organophosphate Flame Retardants in the United States}, volume={4}, ISSN={["2328-8930"]}, DOI={10.1021/acs.estlett.6b00475}, abstractNote={During the past decade, use of organophosphate compounds as flame retardants and plasticizers has increased. Numerous studies investigating biomarkers (i.e., urinary metabolites) demonstrate ubiquitous human exposure and suggest that human exposure may be increasing. To formally assess temporal trends, we combined data from 14 U.S. epidemiologic studies for which our laboratory group previously assessed exposure to two commonly used organophosphate compounds, tris(1,3-dichloro-2-propyl) phosphate (TDCIPP) and triphenyl phosphate (TPHP). Using individual-level data and samples collected between 2002 and 2015, we assessed temporal and seasonal trends in urinary bis(1,3-dichloro-2-propyl) phosphate (BDCIPP) and diphenyl phosphate (DPHP), the metabolites of TDCIPP and TPHP, respectively. Data suggest that BDCIPP concentrations have increased dramatically since 2002. Samples collected in 2014 and 2015 had BDCIPP concentrations that were more than 15 times higher than those collected in 2002 and 2003 (10β = 16.5; 95% confidence interval from 9.64 to 28.3). Our results also demonstrate significant increases in DPHP levels; however, increases were much smaller than for BDCIPP. Additionally, results suggest that exposure varies seasonally, with significantly higher levels of exposure in summer for both TDCIPP and TPHP. Given these increases, more research is needed to determine whether the levels of exposure experienced by the general population are related to adverse health outcomes.}, number={3}, journal={ENVIRONMENTAL SCIENCE & TECHNOLOGY LETTERS}, author={Hoffman, Kate and Butt, Craig M. and Webster, Thomas F. and Preston, Emma V. and Hammel, Stephanie C. and Makey, Colleen and Lorenzo, Amelia M. and Cooper, Ellen M. and Carignan, Courtney and Meeker, John D. and et al.}, year={2017}, month={Mar}, pages={112–118} } @article{zapata_howard_frank_simon_hoyo_grant_freedland_vidal_2017, title={The association between sexual function and prostate cancer risk in US veterans}, volume={19}, ISSN={["1745-7262"]}, DOI={10.4103/1008-682x.184869}, abstractNote={Sexual dysfunction and prostate cancer are common among older men. Few studies explored the association between these two illnesses. We examined whether sexual function is associated with prostate cancer risk among older men. Among 448 men undergoing prostate biopsy at the Durham Veterans Affairs Hospital, sexual function was ascertained from the Expanded Prostate Cancer Index Composite sexual assessment. We tested the link between sexual function and prostate cancer risk adjusting for multiple demographic and clinical characteristics using logistic regression. Multinomial logistic regression was used to test the associations with risk of low-grade (Gleason ≤6) and high-grade (Gleason ≥7 or ≥4 + 3) disease versus no cancer. Of 448 men, 209 (47%) had a positive biopsy; these men were less likely to be white (43% vs 55%, P = 0.013), had higher prostate-specific antigen (PSA) (6.0 vs 5.4 ng ml−1 , P < 0.001), but with lower mean sexual function score (47 vs 54, P = 0.007). There was no difference in age, BMI, pack years smoked, history of heart disease and/or diabetes. After adjusting for baseline differences, sexual function was linked with a decreased risk of overall prostate cancer risk (OR: 0.91 per 10-point change in sexual function, P = 0.004) and high-grade disease whether defined as Gleason ≥7 (OR: 0.86, P = 0.001) or ≥4 + 3 (OR: 0.85, P = 0.009). Sexual function was unrelated to low-grade prostate cancer (OR: 0.94, P = 0.13). Thus, among men undergoing prostate biopsy, higher sexual function was associated with a decreased risk of overall and high-grade prostate cancer. Confirmatory studies are needed.}, number={2}, journal={ASIAN JOURNAL OF ANDROLOGY}, author={Zapata, Daniel F. and Howard, Lauren E. and Frank, Jennifer and Simon, Ross M. and Hoyo, Cathrine and Grant, Delores J. and Freedland, Stephen J. and Vidal, Adriana C.}, year={2017}, pages={191–195} } @article{moylan_mavis_bashir_malik_bozdogan_buie_hoyo_diehl_murphy_abdelmalek_2017, title={Visceral and subcutaneous adipose tissue measurements associate with increased metabolic risk for NAFLD in pre-pubertal obese children}, volume={66}, journal={Hepatology}, author={Moylan, C. A. and Mavis, A. M. and Bashir, M. R. and Malik, D. and Bozdogan, E. and Buie, S. and Hoyo, C. and Diehl, A. M. and Murphy, S. K. and Abdelmalek, M. F.}, year={2017}, pages={665A–665} } @article{fuemmeler_wang_iversen_maguire_murphy_hoyo_2016, title={Association between Prepregnancy Body Mass Index and Gestational Weight Gain with Size, Tempo, and Velocity of Infant Growth: Analysis of the Newborn Epigenetic Study Cohort}, volume={12}, ISSN={["2153-2176"]}, DOI={10.1089/chi.2015.0253}, abstractNote={BACKGROUND The first 1000 days of life is a critical period of infant growth that has been linked to future adult health. Understanding prenatal factors that contribute to variation in growth during this period could inform successful prevention strategies. METHODS Prenatal and maternal characteristics, including prepregnancy obesity and gestational weight gain were evaluated in relation to weight growth trajectories during the first 24 months of life using the SuperImposition by Translation and Rotation (SITAR) method, which provides estimates of infant size, timing to peak velocity, and growth velocity. The study sample included 704 mother-infant dyads from a multiethnic prebirth cohort from the Southeastern United States. The total number of weight measures was 8670 (median number per child = 14). RESULTS Several prenatal and maternal characteristics were linked with infant growth parameters. The primary findings show that compared to women with a prepregnancy BMI between 18 and 24.9, women with a prepregnancy BMI ≥40 had infants that were 8% larger during the first 24 months, a delayed tempo of around 9 days, and a slower velocity. Mothers who had greater than adequate gestational weight gain had infants that were 5% larger even after controlling for prepregnancy BMI and several other covariates. CONCLUSIONS The findings contribute new data on the associations between gestational weight gain and aspects of early growth using the SITAR method, and support a growing consensus in the literature that both prepregnancy BMI and gestational weight gain relate independently to risk for greater postnatal weight growth.}, number={3}, journal={CHILDHOOD OBESITY}, author={Fuemmeler, Bernard F. and Wang, Lin and Iversen, Edwin S. and Maguire, Rachel and Murphy, Susan K. and Hoyo, Cathrine}, year={2016}, month={Jun}, pages={210–218} } @article{joubert_felix_yousefi_bakulski_just_breton_reese_markunas_richmond_xu_et al._2016, title={DNA Methylation in Newborns and Maternal Smoking in Pregnancy: Genome-wide Consortium Meta-analysis}, volume={98}, ISSN={0002-9297}, url={http://dx.doi.org/10.1016/J.AJHG.2016.02.019}, DOI={10.1016/J.AJHG.2016.02.019}, abstractNote={Epigenetic modifications, including DNA methylation, represent a potential mechanism for environmental impacts on human disease. Maternal smoking in pregnancy remains an important public health problem that impacts child health in a myriad of ways and has potential lifelong consequences. The mechanisms are largely unknown, but epigenetics most likely plays a role. We formed the Pregnancy And Childhood Epigenetics (PACE) consortium and meta-analyzed, across 13 cohorts (n = 6,685), the association between maternal smoking in pregnancy and newborn blood DNA methylation at over 450,000 CpG sites (CpGs) by using the Illumina 450K BeadChip. Over 6,000 CpGs were differentially methylated in relation to maternal smoking at genome-wide statistical significance (false discovery rate, 5%), including 2,965 CpGs corresponding to 2,017 genes not previously related to smoking and methylation in either newborns or adults. Several genes are relevant to diseases that can be caused by maternal smoking (e.g., orofacial clefts and asthma) or adult smoking (e.g., certain cancers). A number of differentially methylated CpGs were associated with gene expression. We observed enrichment in pathways and processes critical to development. In older children (5 cohorts, n = 3,187), 100% of CpGs gave at least nominal levels of significance, far more than expected by chance (p value < 2.2 × 10−16). Results were robust to different normalization methods used across studies and cell type adjustment. In this large scale meta-analysis of methylation data, we identified numerous loci involved in response to maternal smoking in pregnancy with persistence into later childhood and provide insights into mechanisms underlying effects of this important exposure. Epigenetic modifications, including DNA methylation, represent a potential mechanism for environmental impacts on human disease. Maternal smoking in pregnancy remains an important public health problem that impacts child health in a myriad of ways and has potential lifelong consequences. The mechanisms are largely unknown, but epigenetics most likely plays a role. We formed the Pregnancy And Childhood Epigenetics (PACE) consortium and meta-analyzed, across 13 cohorts (n = 6,685), the association between maternal smoking in pregnancy and newborn blood DNA methylation at over 450,000 CpG sites (CpGs) by using the Illumina 450K BeadChip. Over 6,000 CpGs were differentially methylated in relation to maternal smoking at genome-wide statistical significance (false discovery rate, 5%), including 2,965 CpGs corresponding to 2,017 genes not previously related to smoking and methylation in either newborns or adults. Several genes are relevant to diseases that can be caused by maternal smoking (e.g., orofacial clefts and asthma) or adult smoking (e.g., certain cancers). A number of differentially methylated CpGs were associated with gene expression. We observed enrichment in pathways and processes critical to development. In older children (5 cohorts, n = 3,187), 100% of CpGs gave at least nominal levels of significance, far more than expected by chance (p value < 2.2 × 10−16). Results were robust to different normalization methods used across studies and cell type adjustment. In this large scale meta-analysis of methylation data, we identified numerous loci involved in response to maternal smoking in pregnancy with persistence into later childhood and provide insights into mechanisms underlying effects of this important exposure.}, number={4}, journal={The American Journal of Human Genetics}, publisher={Elsevier BV}, author={Joubert, Bonnie R. and Felix, Janine F. and Yousefi, Paul and Bakulski, Kelly M. and Just, Allan C. and Breton, Carrie and Reese, Sarah E. and Markunas, Christina A. and Richmond, Rebecca C. and Xu, Cheng-Jian and et al.}, year={2016}, month={Apr}, pages={680–696} } @article{joubert_felix_yousefi_bakulski_just_breton_reese_markunas_richmond_xu_et al._2016, title={DNA methylation in newborns and maternal smoking in pregnancy: Genome-wide consortium meta-analysis}, volume={98}, number={4}, journal={American Journal of Human Genetics}, author={Joubert, B. R. and Felix, J. F. and Yousefi, P. and Bakulski, K. M. and Just, A. C. and Breton, C. and Reese, S. E. and Markunas, C. A. and Richmond, R. C. and Xu, C. J. and et al.}, year={2016}, pages={680–696} } @article{skaar_murphy_hoyo_2016, title={Effects of Environmentally Acquired Heavy Metals and Nutrients on the Epigenome and Phenotype}, ISBN={["978-3-319-27447-8"]}, ISSN={["2168-4219"]}, DOI={10.1007/978-3-319-27449-2_5}, abstractNote={Cadmium, arsenic, mercury and lead are ubiquitous environmental contaminants that tend to co-occur. Unlike organic compounds that are chemically, biologically, or photo-degraded, these metals persist in the environment for indefinite periods. Although protein disruption/misfolding, generation of oxidative stress, and endocrine disruption are known effects of toxic metal exposure, beyond the known toxic effects of high dose exposure, mechanisms causing these effects, especially at low chronic doses, are still largely unknown. Epigenetics is emerging as a viable mechanistic framework to explain how the environment interacts with the genome to alter disease risk. Alterations in DNA methylation, histone marks and chromatin structure have been proposed as useful exposure assessment biomarkers that can substantially improve assessment of risk in etiologic studies where exposure occurs early during the life course. If developed into exposure-specific biomarkers, these epigenetic marks can be a powerful tool to identify populations exposed to low doses where phenotypic response may not be immediately apparent, and also to evaluate the efficacy of therapeutic and public health interventions. This could be particularly important as exposed populations tend to be the socioeconomically disadvantaged who have limited contact with the health care system. In this review, we provide an overview of the current state of literature on heavy-metal-associated epigenetic alterations. We discuss the extent to which such epigenetic alterations alter susceptibility to common chronic diseases and how they might be mitigated by some nutrients, albeit within narrow margins. We conclude by discussing key issues that must be resolved if human epigenetic data is to provide useful biomarkers and mechanistic insights into how low dose chronic exposure to these metals might alter the epigenome and increase disease susceptibility.}, journal={TRANSLATIONAL TOXICOLOGY: DEFINING A NEW THERAPEUTIC DISCIPLINE}, author={Skaar, David A. and Murphy, Susan K. and Hoyo, Cathrine}, year={2016}, pages={139–169} } @article{skaar_jirtle_hoyo_2016, title={Environmentally Induced Alterations in the Epigenome Affecting Obesity and Cancer in Minority Populations}, ISBN={["978-3-319-41608-3"]}, DOI={10.1007/978-3-319-41610-6_5}, abstractNote={The obesity epidemic of the last 30–40 years is may be linked to increased environmental chemical exposures with endocrine disrupting potential. The increases in obesity prevalence and severity coincide with increases in several adenocarcinomas at a time when cancer incidence has been generally declining, with disproportionate effects in different ethnic groups. Despite demonstrated associations between such exposures with obesity, and obesity with these cancers, an association between exposure to these environmental chemicals and adenocarcinomas has been difficult to demonstrate in part due to limits in exposure assessment. Exposure to these compounds elicits stable epigenetic responses; thus, if these alterations to the epigenome can be fully characterized, they can be exploited to improve exposure ascertainment. We summarize in this chapter evidence for the influence of environmental exposures on obesity and how epigenetic alterations may contribute to cancers that disproportionately affect minority populations exhibit disparities in incidence and mortality.}, journal={EPIGENETICS, ENERGY BALANCE, AND CANCER}, author={Skaar, David A. and Jirtle, Randy L. and Hoyo, Cathrine}, year={2016}, pages={109–146} } @article{li_xie_murphy_skaar_nye_vidal_cecil_dietrich_puga_jirtle_et al._2016, title={Lead Exposure during Early Human Development and DNA Methylation of Imprinted Gene Regulatory Elements in Adulthood}, volume={124}, ISSN={["1552-9924"]}, DOI={10.1289/ehp.1408577}, abstractNote={Background: Lead exposure during early development causes neurodevelopmental disorders by unknown mechanisms. Epidemiologic studies have focused recently on determining associations between lead exposure and global DNA methylation; however, such approaches preclude the identification of loci that may alter human disease risk. Objectives: The objective of this study was to determine whether maternal, postnatal, and early childhood lead exposure can alter the differentially methylated regions (DMRs) that control the monoallelic expression of imprinted genes involved in metabolism, growth, and development. Methods: Questionnaire data and serial blood lead levels were obtained from 105 participants (64 females, 41 males) of the Cincinnati Lead Study from birth to 78 months. When participants were adults, we used Sequenom EpiTYPER assays to test peripheral blood DNA to quantify CpG methylation in peripheral blood leukocytes at DMRs of 22 human imprinted genes. Statistical analyses were conducted using linear regression. Results: Mean blood lead concentration from birth to 78 months was associated with a significant decrease in PEG3 DMR methylation (β = –0.0014; 95% CI: –0.0023, –0.0005, p = 0.002), stronger in males (β = –0.0024; 95% CI: –0.0038, –0.0009, p = 0.003) than in females (β = –0.0009; 95% CI: –0.0020, 0.0003, p = 0.1). Elevated mean childhood blood lead concentration was also associated with a significant decrease in IGF2/H19 (β = –0.0013; 95% CI: –0.0023, –0.0003, p = 0.01) DMR methylation, but primarily in females, (β = –0.0017; 95% CI: –0.0029, –0.0006, p = 0.005) rather than in males, (β = –0.0004; 95% CI: –0.0023, 0.0015, p = 0.7). Elevated blood lead concentration during the neonatal period was associated with higher PLAGL1/HYMAI DMR methylation regardless of sex (β = 0.0075; 95% CI: 0.0018, 0.0132, p = 0.01). The magnitude of associations between cumulative lead exposure and CpG methylation remained unaltered from 30 to 78 months. Conclusions: Our findings provide evidence that early childhood lead exposure results in sex-dependent and gene-specific DNA methylation differences in the DMRs of PEG3, IGF2/H19, and PLAGL1/HYMAI in adulthood. Citation: Li Y, Xie C, Murphy SK, Skaar D, Nye M, Vidal AC, Cecil KM, Dietrich KN, Puga A, Jirtle RL, Hoyo C. 2016. Lead exposure during early human development and DNA methylation of imprinted gene regulatory elements in adulthood. Environ Health Perspect 124:666–673; http://dx.doi.org/10.1289/ehp.1408577}, number={5}, journal={ENVIRONMENTAL HEALTH PERSPECTIVES}, author={Li, Yue and Xie, Changchun and Murphy, Susan K. and Skaar, David and Nye, Monica and Vidal, Adriana C. and Cecil, Kim M. and Dietrich, Kim N. and Puga, Alvaro and Jirtle, Randy L. and et al.}, year={2016}, month={May}, pages={666–673} } @article{mccullough_miller_mendez_murtha_murphy_hoyo_2016, title={Maternal B vitamins: effects on offspring weight and DNA methylation at genomically imprinted domains}, volume={8}, journal={Clinical Epigenetics}, author={McCullough, L. E. and Miller, E. E. and Mendez, M. A. and Murtha, A. P. and Murphy, S. K. and Hoyo, C.}, year={2016} } @article{king_kane_scarbrough_hoyo_murphy_2016, title={Neighborhood and Family Environment of Expectant Mothers May Influence Prenatal Programming of Adult Cancer Risk: Discussion and an Illustrative DNA Methylation Example}, volume={62}, ISSN={["1948-5573"]}, DOI={10.1080/19485565.2015.1126501}, abstractNote={Childhood stressors including physical abuse predict adult cancer risk. Prior research portrays this finding as an indirect mechanism that operates through coping behaviors, including adult smoking, or through increased toxic exposures during childhood. Little is known about potential direct causal mechanisms between early-life stressors and adult cancer. Because prenatal conditions can affect gene expression by altering DNA methylation, with implications for adult health, we hypothesize that maternal stress may program methylation of cancer-linked genes during gametogenesis. To illustrate this hypothesis, we related maternal social resources to methylation at the imprinted MEG3 differentially methylated regulatory region, which has been linked to multiple cancer types. Mothers (n = 489) from a diverse birth cohort (Durham, North Carolina) provided newborns’ cord blood and completed a questionnaire. Newborns of currently married mothers showed lower (−0.321 SD, p < .05) methylation compared to newborns of never-married mothers, who did not differ from newborns whose mothers were cohabiting and others (adjusted for demographics). MEG3 DNA methylation levels were also lower when maternal grandmothers co-resided before pregnancy (−0.314 SD, p < .05). A 1-SD increase in prenatal neighborhood disadvantage also predicted higher methylation (−0.137 SD, p < .05). In conclusion, we found that maternal social resources may result in differential methylation of MEG3, which demonstrates a potential partial mechanism priming socially disadvantaged newborns for later risk of some cancers.}, number={1}, journal={BIODEMOGRAPHY AND SOCIAL BIOLOGY}, author={King, Katherine E. and Kane, Jennifer B. and Scarbrough, Peter and Hoyo, Cathrine and Murphy, Susan K.}, year={2016}, month={Jan}, pages={87–104} } @article{soubry_guo_huang_hoyo_romanus_price_murphy_2016, title={Obesity-related DNA methylation at imprinted genes in human sperm: Results from the TIEGER study}, volume={8}, journal={Clinical Epigenetics}, author={Soubry, A. and Guo, L. S. and Huang, Z. Q. and Hoyo, C. and Romanus, S. and Price, T. and Murphy, S. K.}, year={2016} } @article{mccullough_mendez_miller_murtha_murphy_hoyo_2015, title={Associations between prenatal physical activity, birth weight, and DNA methylation at genomically imprinted domains in a multiethnic newborn cohort}, volume={10}, ISSN={["1559-2308"]}, DOI={10.1080/15592294.2015.1045181}, abstractNote={Birth weight is a commonly used indicator of the fetal environment and a predictor of future health outcomes. While the etiology of birth weight extremes is likely multifactorial, epidemiologic data suggest that prenatal physical activity (PA) may play an important role. The mechanisms underlying this association remain unresolved, although epigenetics has been proposed. This study aimed to estimate associations between prenatal PA, birth weight, and newborn DNA methylation levels at differentially methylated regions (DMRs) regulating 4 imprinted genes known to be important in fetal development. Study participants (N = 1281) were enrolled as part of the Newborn Epigenetics Study. Prenatal PA was ascertained using the Pregnancy Physical Activity Questionnaire, and birth weight data obtained from hospital records. Among 484 term mother-infant pairs, imprinted gene methylation levels were measured at DMRs using bisulfite pyrosequencing. Generalized linear and logistic regression models were used to estimate associations. After adjusting for preterm birth and race/ethnicity, we found that infants born to mothers in the highest quartile of total non-sedentary time had lower birth weight compared to infants of mothers in the lowest quartile (β = −81.16, SE = 42.02, P = 0.05). These associations appeared strongest among male infants (β = −125.40, SE = 58.10, P = 0.03). Methylation at the PLAGL1 DMR was related to total non-sedentary time (P < 0.05). Our findings confirm that prenatal PA is associated with reduced birth weight, and is the first study to support a role for imprinted gene plasticity in these associations. Larger studies are required.}, number={7}, journal={EPIGENETICS}, author={McCullough, Lauren E. and Mendez, Michelle A. and Miller, Erline E. and Murtha, Amy P. and Murphy, Susan K. and Hoyo, Cathrine}, year={2015}, month={Jul}, pages={597–606} } @article{neelon_stroo_mayhew_maselko_hoyo_2015, title={Correlation between maternal and infant cortisol varies by breastfeeding status}, volume={40}, ISSN={["1879-0453"]}, DOI={10.1016/j.infbeh.2015.06.005}, abstractNote={The objective of this study was to examine associations of mother and infant salivary cortisol, measured three times over the course of a day, and assess whether these varied by breastfeeding status. We conducted a cross-sectional study of 54 mothers and their infants aged 4–11 months. Mothers collected their own saliva and that of their infants upon awakening, 30 min after waking and at bedtime. Breastfeeding status was reported by mothers and cortisol level was measured in saliva in μg/dl using standard techniques. We used generalized linear models to evaluate relationships between maternal and infant cortisol levels, and assessed whether the relationship differed by breastfeeding status: formula only compared to partial and full breastfeeding, adjusting for infant sex, race, age, maternal education, and family income. Thirty-four infants received formula only and 20 were either partially or fully breastfed. Breastfeeding was associated with higher household income, higher maternal education, and white race. Cortisol levels were higher among breastfed infants at all three time points. After adjustment, maternal cortisol levels were related with infant cortisol at bedtime only (regression estimate 0.06; 95% CI: 0.10, 1.1; p = 0.02). The adjusted association between bedtime maternal and infant cortisol was stronger among breastfeeding dyads than among formula-feeding dyads (regression estimate 1.0; 95% CI: 0.1, 2.0; p = 0.04 vs. 0.6; CI: −0.1, 1.3; p = 0.10). In addition, we assessed the influence of maternal education and household income in our adjusted model; income strengthened the observed association, whereas maternal education did not change the estimate. Breastfeeding mothers and infants had significant correlations for cortisol at bedtime, while formula-feeding dyads did not. These data suggest that several factors may contribute to cortisol synchrony observed in mother/infant dyads, including the transfer of cortisol in human milk, physical interaction such as skin-to-skin contact, and shared environment. In addition, our findings support household income as a possible contributor.}, journal={INFANT BEHAVIOR & DEVELOPMENT}, author={Neelon, Sara E. Benjamin and Stroo, Marissa and Mayhew, Meghan and Maselko, Joanna and Hoyo, Cathrine}, year={2015}, month={Aug}, pages={252–258} } @article{king_murphy_hoyo_2015, title={Epigenetic regulation of Newborns' imprinted genes related to gestational growth: patterning by parental race/ethnicity and maternal socioeconomic status}, volume={69}, ISSN={["1470-2738"]}, DOI={10.1136/jech-2014-204781}, abstractNote={Background Children born to parents with lower income and education are at risk for obesity and later-life risk of common chronic diseases, and epigenetics has been hypothesised to link these associations. However, epigenetic targets are unknown. We focus on a cluster of well-characterised genomically imprinted genes because their monoallelic expression is regulated by DNA methylation at differentially methylated regions (DMRs), are critical in fetal growth, and DNA methylation patterns at birth have been associated with increased risk of birth weight extremes and overweight status or obesity in early childhood. Methods We measured DNA methylation at DMRs regulating genomically imprinted domains (IGF2/H19, DLK1/MEG3, NNAT and PLAGL1) using umbilical cord blood leucocytes from 619 infants recruited in Durham, North Carolina in 2010–2011. We examined differences in DNA methylation levels by race/ethnicity of both parents, and the role that maternal socioeconomic status (SES) may play in the association between race/ethnic epigenetic differences. Results Unadjusted race/ethnic differences only were evident for DMRs regulating MEG3 and IGF2; race/ethnic differences persisted in IGF2/H19 and NNAT after accounting for income and education. Conclusions Results suggest that parental factors may not only influence DNA methylation, but also do so in ways that vary by DMR. Findings support the hypothesis that epigenetics may link the observed lower SES during the prenatal period and poor outcomes such as low birth weight; lower birth weight has previously been associated with adult-onset chronic diseases and conditions that include cardiovascular diseases, diabetes, obesity and some cancers.}, number={7}, journal={JOURNAL OF EPIDEMIOLOGY AND COMMUNITY HEALTH}, author={King, Katherine and Murphy, Susan and Hoyo, Cathrine}, year={2015}, month={Jul}, pages={639–647} } @article{murphy_erginer_huang_visco_hoyo_2015, title={Genotype-epigenotype interaction at the IGF2 DMR}, volume={6}, number={3}, journal={Genes}, author={Murphy, S. K. and Erginer, E. and Huang, Z. Q. and Visco, Z. and Hoyo, C.}, year={2015}, pages={777–789} } @article{king_darrah_money_meentemeyer_maguire_nye_michener_murtha_jirtle_murphy_et al._2015, title={Geographic clustering of elevated blood heavy metal levels in pregnant women}, volume={15}, ISSN={["1471-2458"]}, DOI={10.1186/s12889-015-2379-9}, abstractNote={Cadmium (Cd), lead (Pb), mercury (Hg), and arsenic (As) exposure is ubiquitous and has been associated with higher risk of growth restriction and cardiometabolic and neurodevelopmental disorders. However, cost-efficient strategies to identify at-risk populations and potential sources of exposure to inform mitigation efforts are limited. The objective of this study was to describe the spatial distribution and identify factors associated with Cd, Pb, Hg, and As concentrations in peripheral blood of pregnant women.Heavy metals were measured in whole peripheral blood of 310 pregnant women obtained at gestational age ~12 weeks. Prenatal residential addresses were geocoded and geospatial analysis (Getis-Ord Gi* statistics) was used to determine if elevated blood concentrations were geographically clustered. Logistic regression models were used to identify factors associated with elevated blood metal levels and cluster membership.Geospatial clusters for Cd and Pb were identified with high confidence (p-value for Gi* statistic <0.01). The Cd and Pb clusters comprised 10.5 and 9.2 % of Durham County residents, respectively. Medians and interquartile ranges of blood concentrations (μg/dL) for all participants were Cd 0.02 (0.01-0.04), Hg 0.03 (0.01-0.07), Pb 0.34 (0.16-0.83), and As 0.04 (0.04-0.05). In the Cd cluster, medians and interquartile ranges of blood concentrations (μg/dL) were Cd 0.06 (0.02-0.16), Hg 0.02 (0.00-0.05), Pb 0.54 (0.23-1.23), and As 0.05 (0.04-0.05). In the Pb cluster, medians and interquartile ranges of blood concentrations (μg/dL) were Cd 0.03 (0.02-0.15), Hg 0.01 (0.01-0.05), Pb 0.39 (0.24-0.74), and As 0.04 (0.04-0.05). Co-exposure with Pb and Cd was also clustered, the p-values for the Gi* statistic for Pb and Cd was <0.01. Cluster membership was associated with lower education levels and higher pre-pregnancy BMI.Our data support that elevated blood concentrations of Cd and Pb are spatially clustered in this urban environment compared to the surrounding areas. Spatial analysis of metals concentrations in peripheral blood or urine obtained routinely during prenatal care can be useful in surveillance of heavy metal exposure.}, number={1}, journal={BMC PUBLIC HEALTH}, publisher={Springer Science and Business Media LLC}, author={King, Katherine E. and Darrah, Thomas H. and Money, Eric and Meentemeyer, Ross and Maguire, Rachel L. and Nye, Monica D. and Michener, Lloyd and Murtha, Amy P. and Jirtle, Randy and Murphy, Susan K. and et al.}, year={2015}, month={Oct} } @article{vidal_skaar_maguire_dodor_musselwhite_bartlett_oneko_obure_mlay_murphy_et al._2015, title={IL-10, IL-15, IL-17, and GMCSF levels in cervical cancer tissue of Tanzanian women infected with HPV16/18 vs. non-HPV16/18 genotypes}, volume={10}, journal={Infectious Agents and Cancer}, author={Vidal, A. C. and Skaar, D. and Maguire, R. and Dodor, S. and Musselwhite, L. W. and Bartlett, J. A. and Oneko, O. and Obure, J. and Mlay, P. and Murphy, S. K. and et al.}, year={2015} } @article{nye_hoyo_murphy_2015, title={In vitro lead exposure changes DNA methylation and expression of IGF2 and PEG1/MEST}, volume={29}, ISSN={["1879-3177"]}, DOI={10.1016/j.tiv.2015.01.002}, abstractNote={Epigenetic processes, such as changes in DNA methylation, likely mediate the link between environmental exposures in utero and altered gene expression. Differentially methylated regions (DMRs) that regulate imprinted genes may be especially vulnerable to environmental exposures since imprinting is established and maintained largely through DNA methylation, resulting in expression from only one parental chromosome. We used the human embryonic kidney cell line, HEK-293, to investigate the effects of exposure to physiologically relevant doses of lead acetate (Pb) on the methylation status of nine imprinted gene DMRs. We assessed mean methylation after seventy-two hours of Pb exposure (0–25 μg/dL) using bisulfite pyrosequencing. The PEG1/MEST and IGF2 DMRs had maximum methylation decreases of 9.6% (20 μg/dL; p < 0.005) and 3.8% (25 μg/dL; p < 0.005), respectively. Changes at the MEG3 DMRs had a maximum decrease in methylation of 2.9% (MEG3) and 1.8% (MEG3-IG) at 5 μg/dL Pb, but were not statistically significant. The H19, NNAT, PEG3, PLAGL1, and SGCE/PEG10 DMRs showed a less than 0.5% change in methylation, across the dose range used, and were deemed non-responsive to Pb in our model. Pb exposure below reportable/actionable levels increased expression of PEG1/MEST concomitant with decreased methylation. These results suggest that Pb exposure can stably alter the regulatory capacity of multiple imprinted DMRs.}, number={3}, journal={TOXICOLOGY IN VITRO}, author={Nye, Monica D. and Hoyo, Cathrine and Murphy, Susan K.}, year={2015}, month={Apr}, pages={544–550} } @article{zapata_howard_frank_ross_hoyo_grant_freedland_vidal_2015, title={MP14-06 SELF-REPORTED SEXUAL FUNCTION IS ASSOCIATED WITH PROSTATE CANCER RISK}, volume={193}, ISSN={0022-5347 1527-3792}, url={http://dx.doi.org/10.1016/J.JURO.2015.02.868}, DOI={10.1016/J.JURO.2015.02.868}, abstractNote={You have accessJournal of UrologyProstate Cancer: Epidemiology & Natural History III1 Apr 2015MP14-06 SELF-REPORTED SEXUAL FUNCTION IS ASSOCIATED WITH PROSTATE CANCER RISK Daniel Zapata, Lauren E. Howard, Jennifer Frank, Simon Ross, Catherine Hoyo, Dolores Grant, Stephen J. Freedland, and Adriana C. Vidal Daniel ZapataDaniel Zapata More articles by this author , Lauren E. HowardLauren E. Howard More articles by this author , Jennifer FrankJennifer Frank More articles by this author , Simon RossSimon Ross More articles by this author , Catherine HoyoCatherine Hoyo More articles by this author , Dolores GrantDolores Grant More articles by this author , Stephen J. FreedlandStephen J. Freedland More articles by this author , and Adriana C. VidalAdriana C. Vidal More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2015.02.868AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Introduction and objectives: Erectile dysfunction and prostate cancer (PC) are prevalent conditions among older men. To date, few studies have explored the association between these two conditions. Therefore, we tested if there is an association between sexual function and the risk of PC among men undergoing prostate biopsy. METHODS We reviewed data of 448 men undergoing prostate biopsy at a Veterans Affairs Medical Center. Sexual function data were obtained from the Expanded Prostate Cancer Index Composite sexual assessment which queries ability to have an erection, reach an orgasm, quality and frequency of erections, overall sexual function and a bother index. Most questions had a score from 1–5 (1=very poor, 5=very good). Each number was mapped to a 0–100 score and scores were averaged to create an overall sexual function score ranging from 0–100. Men with a positive biopsy were divided into low- (Gleason≤6) and high-grade (Gleason ≥7) disease. Logistic regression was used to test the link between sexual function and PC risk. Multinomial logistic regression was used to test the association between sexual function and risk of low-grade vs. no cancer and risk of high-grade vs. no cancer. RESULTS 209 (47%) men had a positive biopsy; these men were less likely to be white (43% vs. 55%, p=0.01), more recently accrued (2010 vs. 2009, p=0.002), had higher PSA (6.0 vs. 5.4ng/ml, p<0.001) but lower mean sexual function score (47 vs. 54, p<0.001). There was no difference in age, BMI, pack years smoked, history of heart disease and/or diabetes. Sexual function was linked with a decreased risk of overall PC risk (OR 0.91 per 10-pt change in sexual function, p=0.004) and high grade disease (OR 0.86, p=0.001). There was no association between sexual function and low grade PC. CONCLUSIONS Among men undergoing prostate biopsy, higher sexual function was associated with a decreased risk of overall and high-grade PC. Confirmatory studies are needed. © 2015 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 193Issue 4SApril 2015Page: e152-e153 Advertisement Copyright & Permissions© 2015 by American Urological Association Education and Research, Inc.MetricsAuthor Information Daniel Zapata More articles by this author Lauren E. Howard More articles by this author Jennifer Frank More articles by this author Simon Ross More articles by this author Catherine Hoyo More articles by this author Dolores Grant More articles by this author Stephen J. Freedland More articles by this author Adriana C. Vidal More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...}, number={4S}, journal={Journal of Urology}, publisher={Ovid Technologies (Wolters Kluwer Health)}, author={Zapata, Daniel and Howard, Lauren E. and Frank, Jennifer and Ross, Simon and Hoyo, Catherine and Grant, Dolores and Freedland, Stephen J. and Vidal, Adriana C.}, year={2015}, month={Apr} } @article{guerrios_howard_sourbeer_arulraja_beverly_grant_hoyo_freedland_2015, title={MP14-11 IS BMI THE BEST ADIPOSITY MEASURE FOR PROSTATE CANCER RISK?}, volume={193}, ISSN={0022-5347 1527-3792}, url={http://dx.doi.org/10.1016/J.JURO.2015.02.873}, DOI={10.1016/J.JURO.2015.02.873}, abstractNote={You have accessJournal of UrologyProstate Cancer: Epidemiology & Natural History III1 Apr 2015MP14-11 IS BMI THE BEST ADIPOSITY MEASURE FOR PROSTATE CANCER RISK? Lourdes Guerrios, Lauren Howard, Katherine Sourbeer, Evangeline Arulraja, Devon Beverly, Delores J. Grant, Catherine Hoyo, and Steve Freedland Lourdes GuerriosLourdes Guerrios More articles by this author , Lauren HowardLauren Howard More articles by this author , Katherine SourbeerKatherine Sourbeer More articles by this author , Evangeline ArulrajaEvangeline Arulraja More articles by this author , Devon BeverlyDevon Beverly More articles by this author , Delores J. GrantDelores J. Grant More articles by this author , Catherine HoyoCatherine Hoyo More articles by this author , and Steve FreedlandSteve Freedland More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2015.02.873AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES The association between body mass index (BMI) and prostate cancer (PC) risk is mixed. Some have speculated that this relates to the fact that BMI is only a moderate measure of adiposity and that perhaps better measures (total percent body fat) or that central adiposity (waist circumference) may better correlate with PC risk. We tested multiple measures of adiposity and PC risk using prospectively collected and measured data from men undergoing prostate biopsies in a Veterans Affairs hospital. We hypothesized that on the aggregate level, BMI, total percent body fat and waist circumference would be highly correlated and that all would be associated with aggressive PC, but not overall incidence. METHODS We used data from a case-control study among veterans between 2007 and 2012 undergoing prostate biopsy at the Durham Veterans Affairs. The sample consisted of 323 (46%) with biopsy-positive PC (cases) and 375 (54%) biopsy negative (controls). We abstracted Gleason score and race from the records. Weight, height, and waist circumference were measured by trained personnel. Body fat was measured using bio-impedance. We used logistic regression to obtain odds ratios (ORs) and 95% confidence intervals (CIs) to test the association between adiposity measures and PC risk. Multinomial logistic regression was used to examined high-grade PC (Gleason 7–10) vs. low-grade (2–6) vs. no-PC. RESULTS BMI was strongly related to percent body fat (Spearman, r=0.81) and waist circumference (r=0.87). Men with higher BMI had significantly higher TRUS prostate volumes, percent body fat, and waist circumference. In both adjusted and unadjusted logistic regression analyses, all three adiposity measures were unrelated to total PC risk (all p>=0.14). However, when stratified by Gleason score, all adiposity measures were associated with a significantly increased risk of high-grade disease (all p<0.009) but none were related to low-grade PC (all p>=0.35). CONCLUSIONS BMI, body fat and waist circumference are all highly correlated with each other and all were significantly associated with aggressive PC, but not overall PC risk. Despite individual differences in these measures, this study supports the continued use of BMI in epidemiological studies of obesity and PC. © 2015 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 193Issue 4SApril 2015Page: e155 Advertisement Copyright & Permissions© 2015 by American Urological Association Education and Research, Inc.MetricsAuthor Information Lourdes Guerrios More articles by this author Lauren Howard More articles by this author Katherine Sourbeer More articles by this author Evangeline Arulraja More articles by this author Devon Beverly More articles by this author Delores J. Grant More articles by this author Catherine Hoyo More articles by this author Steve Freedland More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...}, number={4S}, journal={Journal of Urology}, publisher={Ovid Technologies (Wolters Kluwer Health)}, author={Guerrios, Lourdes and Howard, Lauren and Sourbeer, Katherine and Arulraja, Evangeline and Beverly, Devon and Grant, Delores J. and Hoyo, Catherine and Freedland, Steve}, year={2015}, month={Apr} } @article{vidal_semenova_darrah_vengosh_huang_king_nye_fry_skaar_maguire_et al._2015, title={Maternal cadmium, iron and zinc levels, DNA methylation and birth weight}, volume={16}, journal={BMC Pharmacology & Toxicology}, author={Vidal, A. C. and Semenova, V. and Darrah, T. and Vengosh, A. and Huang, Z. Q. and King, K. and Nye, M. D. and Fry, R. and Skaar, D. and Maguire, R. and et al.}, year={2015} } @article{soubry_hoyo_jirtle_murphy_2014, title={A paternal environmental legacy: Evidence for epigenetic inheritance through the male germ line}, volume={36}, ISSN={0265-9247}, url={http://dx.doi.org/10.1002/BIES.201300113}, DOI={10.1002/BIES.201300113}, abstractNote={Abstract}, number={4}, journal={BioEssays}, publisher={Wiley}, author={Soubry, Adelheid and Hoyo, Cathrine and Jirtle, Randy L. and Murphy, Susan K.}, year={2014}, month={Jan}, pages={359–371} } @article{vidal_williams_allott_howard_grant_mcphail_sourbeer_hwa_boffetta_hoyo_et al._2014, title={Carbohydrate intake, glycemic index and prostate cancer risk}, volume={75}, ISSN={0270-4137}, url={http://dx.doi.org/10.1002/PROS.22929}, DOI={10.1002/PROS.22929}, abstractNote={Reported associations between dietary carbohydrate and prostate cancer (PC) risk are poorly characterized by race.}, number={4}, journal={The Prostate}, publisher={Wiley}, author={Vidal, Adriana C. and Williams, Christina D. and Allott, Emma H. and Howard, Lauren E. and Grant, Delores J. and McPhail, Megan and Sourbeer, Katharine N. and Hwa, Lin Pao and Boffetta, Paolo and Hoyo, Cathrine and et al.}, year={2014}, month={Nov}, pages={430–439} } @article{soubry_verbeke_hoyo_2014, title={Do early paternal exposures to lifestyle factors such as smoking increase the risk of chronic diseases in the offspring?}, volume={22}, ISSN={1018-4813 1476-5438}, url={http://dx.doi.org/10.1038/EJHG.2014.206}, DOI={10.1038/EJHG.2014.206}, abstractNote={Do early paternal exposures to lifestyle factors such as smoking increase the risk of chronic diseases in the offspring?}, number={12}, journal={European Journal of Human Genetics}, publisher={Springer Science and Business Media LLC}, author={Soubry, Adelheid and Verbeke, Geert and Hoyo, Cathrine}, year={2014}, month={Oct}, pages={1341–1342} } @article{hoyo_daltveit_iversen_benjamin-neelon_fuemmeler_schildkraut_murtha_overcash_vidal_wang_et al._2014, title={Erythrocyte folate concentrations, CpG methylation at genomically imprinted domains, and birth weight in a multiethnic newborn cohort}, volume={9}, ISSN={["1559-2308"]}, DOI={10.4161/epi.29332}, abstractNote={Epigenetic mechanisms are proposed to link maternal concentrations of methyl group donor nutrients with the risk of low birth weight. However, empirical data are lacking. We have examined the association between maternal folate and birth weight and assessed the mediating role of DNA methylation at nine differentially methylated regions (DMRs) of genomically imprinted genes in these associations. Compared with newborns of women with folate levels in the lowest quartile, birth weight was higher in newborns of mothers in the second (β = 143.2, se = 63.2, P = 0.02), third (β = 117.3, se = 64.0, P = 0.07), and fourth (β = 133.9, se = 65.2, P = 0.04) quartiles, consistent with a threshold effect. This pattern of association did not vary by race/ethnicity but was more apparent in newborns of non-obese women. DNA methylation at the PLAGL1, SGCE, DLK1/MEG3 and IGF2/H19 DMRs was associated with maternal folate levels and also birth weight, suggestive of threshold effects. MEG3 DMR methylation mediated the association between maternal folate levels and birth weight (P =0.06). While the small sample size and partial scope of examined DMRs limit our conclusions, our data suggest that, with respect to birth weight, no additional benefits may be derived from increased maternal folate concentrations, especially in non-obese women. These data also support epigenetic plasticity as a key mechanistic response to folate availability during early fetal development.}, number={8}, journal={EPIGENETICS}, author={Hoyo, Cathrine and Daltveit, Anne Kjersti and Iversen, Edwin and Benjamin-Neelon, Sara E. and Fuemmeler, Bernard and Schildkraut, Joellen and Murtha, Amy P. and Overcash, Francine and Vidal, Adriana C. and Wang, Frances and et al.}, year={2014}, month={Aug}, pages={1120–1130} } @article{vidal_smith_valea_bentley_gradison_yarnall_ford_overcash_grant_murphy_et al._2014, title={HPV genotypes and cervical intraepithelial neoplasia in a multiethnic cohort in the southeastern USA}, volume={25}, ISSN={["1573-7225"]}, DOI={10.1007/s10552-014-0406-2}, abstractNote={For poorly understood reasons, invasive cervical cancer (ICC) incidence and mortality rates are higher in women of African descent. Oncogenic human papillomavirus (HPV) genotypes distribution may vary between European American (EA) and African-American (AA) women and may contribute to differences in ICC incidence. The current study aimed at disentangling differences in HPV distribution among AA and EA women.Five-hundred and seventy-two women were enrolled at the time of colposcopic evaluation following an abnormal liquid-based cytology screen. HPV infections were detected using HPV linear array, and chi-squared tests and linear regression models were used to compare HPV genotypes across racial/ethnic groups by CIN status.Of the 572 participants, 494 (86 %) had detectable HPV; 245 (43 %) had no CIN lesion, 239 (42 %) had CIN1, and 88 (15 %) had CIN2/3. Seventy-three percent of all women were infected with multiple HPV genotypes. After adjusting for race, age, parity, income, oral contraception use, and current smoking, AAs were two times less likely to harbor HPV 16/18 (OR 0.48, 95 % CI 0.21-0.94, p = 0.03) when all women were considered. This association remained unchanged when only women with CIN2/3 lesions were examined (OR 0.22, 95 % CI 0.05-0.95, p = 0.04). The most frequent high-risk HPV genotypes detected among EAs were 16, 18, 56, 39, and 66, while HPV genotypes 33, 35, 45, 58, and 68 were the most frequent ones detected in AAs.Our data suggest that while HPV 16/18 are the most common genotypes among EA women with CIN, AAs may harbor different genotypes.}, number={8}, journal={CANCER CAUSES & CONTROL}, author={Vidal, Adriana C. and Smith, Jennifer S. and Valea, Fidel and Bentley, Rex and Gradison, Maggie and Yarnall, Kimberly S. H. and Ford, Anne and Overcash, Francine and Grant, Kathy and Murphy, Susan K. and et al.}, year={2014}, month={Aug}, pages={1055–1062} } @article{vidal_williams_allott_howard_grant_mcphail_sourbeer_boffetta_hoyo_freedland_2014, title={PD31-11 CARBOHYDRATE INTAKE, GLYCEMIC INDEX AND PROSTATE CANCER RISK}, volume={191}, ISSN={0022-5347 1527-3792}, url={http://dx.doi.org/10.1016/J.JURO.2014.02.2270}, DOI={10.1016/J.JURO.2014.02.2270}, abstractNote={You have accessJournal of UrologyProstate Cancer: Epidemiology & Natural History I1 Apr 2014PD31-11 CARBOHYDRATE INTAKE, GLYCEMIC INDEX AND PROSTATE CANCER RISK Adriana C. Vidal, Christina Williams, Emma H. Allott, Lauren E. Howard, Delores J. Grant, Megan McPhail, Katharine N. Sourbeer, Paolo Boffetta, Cathrine Hoyo, and Stephen J. Freedland Adriana C. VidalAdriana C. Vidal More articles by this author , Christina WilliamsChristina Williams More articles by this author , Emma H. AllottEmma H. Allott More articles by this author , Lauren E. HowardLauren E. Howard More articles by this author , Delores J. GrantDelores J. Grant More articles by this author , Megan McPhailMegan McPhail More articles by this author , Katharine N. SourbeerKatharine N. Sourbeer More articles by this author , Paolo BoffettaPaolo Boffetta More articles by this author , Cathrine HoyoCathrine Hoyo More articles by this author , and Stephen J. FreedlandStephen J. Freedland More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2014.02.2270AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Reported associations between dietary carbohydrate and prostate cancer (PC) risk are inconsistent and poorly characterized by race. We examined the associations between dietary carbohydrate intake, glycemic index (GI), and PC risk in blacks and whites. METHODS We analyzed data from an ongoing case-control study of white (N=262) and black (N=168) veterans at the Durham VA Hospital. Cases were 156 men with biopsy-confirmed PC. Controls were men who had undergone PSA testing but were not recommended for further evaluation. Demographic and lifestyle risk data were collected using self-administered questionnaires prior to diagnosis. Diet information was obtained using the Harvard food frequency questionnaire. Logistic regression models were used to estimate PC risk and results were adjusted for age, race, body mass index and caloric intake. RESULTS Among controls, median carbohydrate intake was 224 gms/day, which amounted to 49% (IQR 43-55%) of calories from carbohydrates. Higher total carbohydrate intake was associated with reduced PC risk (3rd tertile vs. 1st tertile, OR=0.29, 95%CI 0.11-0.72, p-trend=0.007). Though associations were similar in black and white men, this only reached significance in black men (p-trend=0.007). When carbohydrate intake was measured as percent of energy from carbohydrates, higher intake was associated with reduced PC risk (3rd tertile vs. 1st tertile, OR=0.57, 95%CI 0.34-0.96, p=0.033). Again, results were similar in both races, though this only reached significance in black men (p-trend=0.025). Similarly, higher fiber intake (p-trend=0.047) was associated with lower risk of PC, with results similar in black and white men. In contrast, GI was unrelated to PC risk among all men with a suggestion that higher GI may be linked with increased PC risk in black men (p-trend=0.06). When stratified by grade, associations for all dietary factors examined were similar for both low- and high-grade disease. CONCLUSIONS Among men consuming a Western diet, our findings suggest higher carbohydrate intake and thereby lower intake of other macronutrients (i.e. protein and fat) may be associated with reduced risk of overall PC and both low- and high-grade PC. However, when examining the GI of the diet, there was no association, although there was a suggestion that high GI foods may increase PC risk in black men. While larger studies are needed to confirm our findings, these data suggest that among men consuming a Western diet, those eating more complex carbohydrates (i.e. fiber, whole grains) but not refined carbohydrates may have lower PC risk. © 2014FiguresReferencesRelatedDetails Volume 191Issue 4SApril 2014Page: e835 Advertisement Copyright & Permissions© 2014MetricsAuthor Information Adriana C. Vidal More articles by this author Christina Williams More articles by this author Emma H. Allott More articles by this author Lauren E. Howard More articles by this author Delores J. Grant More articles by this author Megan McPhail More articles by this author Katharine N. Sourbeer More articles by this author Paolo Boffetta More articles by this author Cathrine Hoyo More articles by this author Stephen J. Freedland More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...}, number={4S}, journal={Journal of Urology}, publisher={Ovid Technologies (Wolters Kluwer Health)}, author={Vidal, Adriana C. and Williams, Christina and Allott, Emma H. and Howard, Lauren E. and Grant, Delores J. and McPhail, Megan and Sourbeer, Katharine N. and Boffetta, Paolo and Hoyo, Cathrine and Freedland, Stephen J.}, year={2014}, month={Apr} } @article{gaines_turner_moorman_freedland_keto_mcphail_grant_vidal_hoyo_2014, title={The association between race and prostate cancer risk on initial biopsy in an equal access, multiethnic cohort}, volume={25}, ISSN={0957-5243 1573-7225}, url={http://dx.doi.org/10.1007/S10552-014-0402-6}, DOI={10.1007/S10552-014-0402-6}, abstractNote={Population-based studies have established a link between race and prostate cancer (PC) risk, but whether race predicts PC after adjusting for clinical characteristics is unclear. We investigated the association between race and risk of low- and high-grade PC in men undergoing initial prostate biopsy in an equal access medical center. We conducted a retrospective record review of 887 men (48.6 % black, 51.4 % white) from the Durham Veterans Affairs Medical Center who underwent initial prostate biopsy between 2001 and 2009. Multivariable logistic regression analysis of race and biopsy outcome was conducted adjusting for age, body mass index, number of cores taken, prostate-specific antigen (PSA), and digital rectal examination findings. Multinomial logistic regression was used to test the association between black race and PC grade (Gleason <7 vs. ≥7). Black men were younger at biopsy (61 vs. 65 years, p < 0.001) and had a higher pre-biopsy PSA (6.6 vs. 5.8 ng/ml, p = 0.001). A total of 499 men had PC on biopsy (245 low grade; 254 high grade). In multivariable analyses, black race was significantly predictive of PC overall [odds ratio 1.50, p = 0.006] and high-grade PC [relative risk ratio (RRR) 1.84, p = 0.001], but was not significantly associated with low-grade PC (RRR 1.29, p = 0.139). In an equal access healthcare facility, black race was associated with greater risk of PC detection on initial biopsy and of high-grade PC after adjusting for clinical characteristics. Additional investigation of mechanisms linking black race and PC risk and PC aggressiveness is needed.}, number={8}, journal={Cancer Causes & Control}, publisher={Springer Science and Business Media LLC}, author={Gaines, Alexis R. and Turner, Elizabeth L. and Moorman, Patricia G. and Freedland, Stephen J. and Keto, Christopher J. and McPhail, Megan E. and Grant, Delores J. and Vidal, Adriana C. and Hoyo, Cathrine}, year={2014}, month={May}, pages={1029–1035} } @article{liu_hoyo_murphy_overcash_thompson_brown_murtha_2013, title={75: DNA methylation at imprinted regulatory regions in preterm birth and infection}, volume={208}, ISSN={0002-9378}, url={http://dx.doi.org/10.1016/j.ajog.2012.10.240}, DOI={10.1016/j.ajog.2012.10.240}, number={1}, journal={American Journal of Obstetrics and Gynecology}, publisher={Elsevier BV}, author={Liu, Ying and Hoyo, Cathrine and Murphy, Susan and Overcash, Francine and Thompson, Jennifer and Brown, Haywood and Murtha, Amy}, year={2013}, month={Jan}, pages={S45} } @article{thomas_antonelli_banez_hoyo_grant_demark-wahnefried_platz_gerber_shuler_eyoh_et al._2013, title={Androgenetic alopecia at various ages and prostate cancer risk in an equal-access multiethnic case–control series of veterans}, volume={24}, ISSN={0957-5243 1573-7225}, url={http://dx.doi.org/10.1007/S10552-013-0182-4}, DOI={10.1007/S10552-013-0182-4}, abstractNote={Epidemiological data are conflicting regarding the association between androgenetic alopecia (AA) and prostate cancer (CaP). We examined the relationship between these two conditions. We performed a case–control study at a Veterans Affairs Hospital among 708 men: 312 healthy controls, 167 men with CaP, and 229 men without CaP on prostate biopsy. Participants were asked to self-describe hair patterns at ages 30 and 40 and at study enrollment. We tested the association between hair pattern (overall, vertex, or frontal) and CaP status using logistic regression analysis adjusting for multiple clinical features. Disease grade was similarly examined as a secondary outcome. Relative to healthy controls, younger age of AA onset was significantly associated with increased CaP risk (p = 0.008). Similar patterns were noted for frontal (p = 0.005) and not vertex balding (p = 0.22). When compared with biopsy-negative men, a similar pattern was seen with younger age of AA onset having higher risk of CaP, though this was not significant (p = 0.07). A suggestion for younger age of AA onset for frontal (p = 0.07) being associated with CaP versus biopsy-negative men was also observed. Overall balding (yes/no) was associated with greater than twofold increase in high-grade disease (p = 0.02). Men reporting earlier AA onset were at increased CaP risk and suggestively had more aggressive disease. Contrary to other studies, frontal balding was the predominant pattern associated with elevated CaP risk. Further study is required to confirm these findings in a larger sample and to better understand the role of AA, androgens, and CaP biology.}, number={5}, journal={Cancer Causes & Control}, publisher={Springer Science and Business Media LLC}, author={Thomas, Jean-Alfred and Antonelli, Jodi A. and Banez, Lionel L. and Hoyo, Catherine and Grant, Delores and Demark-Wahnefried, Wendy and Platz, Elizabeth A. and Gerber, Leah and Shuler, Kathryn and Eyoh, Enwono and et al.}, year={2013}, month={Mar}, pages={1045–1052} } @article{singh_jones_antonelli_gerber_calloway_shuler_freedland_grant_hoyo_bañez_2013, title={Association between exercise and primary incidence of prostate cancer}, volume={119}, ISSN={0008-543X}, url={http://dx.doi.org/10.1002/CNCR.27791}, DOI={10.1002/CNCR.27791}, abstractNote={Abstract}, number={7}, journal={Cancer}, publisher={Wiley}, author={Singh, Abhay A. and Jones, Lee W. and Antonelli, Jodi A. and Gerber, Leah and Calloway, Elizabeth E. and Shuler, Kathleen H. and Freedland, Stephen J. and Grant, Delores J. and Hoyo, Cathrine and Bañez, Lionel L.}, year={2013}, month={Feb}, pages={1338–1343} } @article{vidal_murphy_murtha_schildkraut_soubry_huang_neelon_fuemmeler_iversen_wang_et al._2013, title={Associations between antibiotic exposure during pregnancy, birth weight and aberrant methylation at imprinted genes among offspring}, volume={37}, ISSN={0307-0565 1476-5497}, url={http://dx.doi.org/10.1038/IJO.2013.47}, DOI={10.1038/IJO.2013.47}, abstractNote={Low birth weight (LBW) has been associated with common adult-onset chronic diseases, including obesity, cardiovascular disease, type II diabetes and some cancers. The etiology of LBW is multi-factorial. However, recent evidence suggests exposure to antibiotics may also increase the risk of LBW. The mechanisms underlying this association are unknown, although epigenetic mechanisms are hypothesized. In this study, we evaluated the association between maternal antibiotic use and LBW and examined the potential role of altered DNA methylation that controls growth regulatory imprinted genes in these associations.Between 2009-2011, 397 pregnant women were enrolled and followed until delivery. Prenatal antibiotic use was ascertained through maternal self-report. Imprinted genes methylation levels were measured at differentially methylated regions (DMRs) using bisulfite pyrosequencing. Generalized linear models were used to examine associations among antibiotic use, birth weight and DMR methylation fractions.After adjusting for infant gender, race/ethnicity, maternal body mass index, delivery route, gestational weight gain, gestational age at delivery, folic acid intake, physical activity, maternal smoking and parity, antibiotic use during pregnancy was associated with 138 g lower birth weight compared with non-antibiotic use (β-coefficient=-132.99, s.e.=50.70, P=0.008). These associations were strongest in newborns of women who reported antibiotic use other than penicillins (β-coefficient=-135.57, s.e.=57.38, P=0.02). Methylation at five DMRs, IGF2 (P=0.05), H19 (P=0.15), PLAGL1 (P=0.01), MEG3 (P=0.006) and PEG3 (P=0.08), was associated with maternal antibiotic use; among these, only methylation at the PLAGL1 DMR was also associated with birth weight.We report an inverse association between in utero exposure to antibiotics and lower infant birth weight and provide the first empirical evidence supporting imprinted gene plasticity in these associations.}, number={7}, journal={International Journal of Obesity}, publisher={Springer Science and Business Media LLC}, author={Vidal, A C and Murphy, S K and Murtha, A P and Schildkraut, J M and Soubry, A and Huang, Z and Neelon, S E B and Fuemmeler, B and Iversen, E and Wang, F and et al.}, year={2013}, month={Mar}, pages={907–913} } @article{liu_hoyo_murphy_huang_overcash_thompson_brown_murtha_2013, title={DNA methylation at imprint regulatory regions in preterm birth and infection}, volume={208}, ISSN={0002-9378}, url={http://dx.doi.org/10.1016/J.AJOG.2013.02.006}, DOI={10.1016/J.AJOG.2013.02.006}, abstractNote={To aid in understanding long-term health consequences of intrauterine infections in preterm birth, we evaluated DNA methylation at 9 differentially methylated regions that regulate imprinted genes by type of preterm birth (spontaneous preterm labor, preterm premature rupture of membranes, or medically indicated [fetal growth restriction and preeclampsia]) and infection status (chorioamnionitis or funisitis).Data on type of preterm birth and infection status were abstracted from medical records and standardized pathology reports in 73 preterm infants enrolled in the Newborn Epigenetics STudy, a prospective cohort study of mother-infant dyads in Durham, NC. Cord blood was collected at birth, and infant DNA methylation levels at the H19, IGF2, MEG3, MEST, SGCE/PEG10, PEG3, NNAT, and PLAGL1 differentially methylated regions were measured using bisulfite pyrosequencing. One-way analyses of variance and logistic regression models were used to compare DNA methylation levels by type of preterm birth and infection status.DNA methylation levels did not differ at any of the regions (P > .20) between infants born via spontaneous preterm labor (average n = 29), preterm premature rupture of membranes (average n = 17), or medically indicated preterm birth (average n = 40). Levels were significantly increased at PLAGL1 in infants with chorioamnionitis (n = 10, 64.4%) compared with infants without chorioamnionitis (n = 63, 57.9%), P < .01. DNA methylation levels were also increased at PLAGL1 for infants with funisitis (n = 7, 63.3%) compared with infants without funisitis (n = 66, 58.3%), P < .05.Dysregulation of PLAGL1 has been associated with abnormal development and cancer. Early-life exposures, including infection/inflammation, may affect epigenetic changes that increase susceptibility to later chronic disease.}, number={5}, journal={American Journal of Obstetrics and Gynecology}, publisher={Elsevier BV}, author={Liu, Ying and Hoyo, Cathrine and Murphy, Susan and Huang, Zhiqing and Overcash, Francine and Thompson, Jennifer and Brown, Haywood and Murtha, Amy P.}, year={2013}, month={May}, pages={395.e1–395.e7} } @article{fish_moorman_wordlaw-stintson_vidal_smith_hoyo_2013, title={Factors Associated With Adherence to Follow-up Colposcopy}, volume={44}, ISSN={1932-5037 2168-3751}, url={http://dx.doi.org/10.1080/19325037.2013.838881}, DOI={10.1080/19325037.2013.838881}, abstractNote={Background Understanding the gaps in knowledge about human papilloma virus (HPV) infection, transmission, and health consequences and factors associated with the knowledge gap is an essential first step for the development of interventions to improve adherence to follow-up among women with abnormal Pap smears. Purpose To examine the relationship between knowledge about HPV and adherence to scheduled colposcopic evaluation and variables related to lack of knowledge among women with abnormal Pap tests. Methods Telephone surveys were conducted with women who attended their scheduled appointments (adherers) and women who did not attend their appointments (nonadherers). Results The multivariable analyses indicate that lower HPV knowledge was independently associated with nonadherence to follow-up, controlling for race and education level. Factors related to lower knowledge scores included non-white race, lower education, and lack of health insurance at the time of the scheduled appointment. Conclusion Lack of knowledge of HPV was related to nonadherence among women scheduled for colposcopic evaluation. Translation to Health Education Practice Health education interventions that deliver complex information about HPV and cervical cancer should be in a format that is accessible and understandable to the women who are most at risk of being nonadherent.}, number={6}, journal={American Journal of Health Education}, publisher={Informa UK Limited}, author={Fish, Laura J. and Moorman, Patricia G. and Wordlaw-Stintson, Lashawn and Vidal, Adriana and Smith, Jennifer S. and Hoyo, Cathrine}, year={2013}, month={Nov}, pages={293–298} } @article{soubry_murphy_wang_huang_vidal_fuemmeler_kurtzberg_murtha_jirtle_schildkraut_et al._2013, title={Newborns of obese parents have altered DNA methylation patterns at imprinted genes}, volume={39}, ISSN={0307-0565 1476-5497}, url={http://dx.doi.org/10.1038/IJO.2013.193}, DOI={10.1038/IJO.2013.193}, abstractNote={Several epidemiologic studies have demonstrated associations between periconceptional environmental exposures and health status of the offspring in later life. Although these environmentally related effects have been attributed to epigenetic changes, such as DNA methylation shifts at imprinted genes, little is known about the potential effects of maternal and paternal preconceptional overnutrition or obesity.We examined parental preconceptional obesity in relation to DNA methylation profiles at multiple human imprinted genes important in normal growth and development, such as: maternally expressed gene 3 (MEG3), mesoderm-specific transcript (MEST), paternally expressed gene 3 (PEG3), pleiomorphic adenoma gene-like 1 (PLAGL1), epsilon sarcoglycan and paternally expressed gene 10 (SGCE/PEG10) and neuronatin (NNAT).We measured methylation percentages at the differentially methylated regions (DMRs) by bisulfite pyrosequencing in DNA extracted from umbilical cord blood leukocytes of 92 newborns. Preconceptional obesity, defined as BMI ⩾30 kg m(-2), was ascertained through standardized questionnaires.After adjusting for potential confounders and cluster effects, paternal obesity was significantly associated with lower methylation levels at the MEST (β=-2.57; s.e.=0.95; P=0.008), PEG3 (β=-1.71; s.e.=0.61; P=0.005) and NNAT (β=-3.59; s.e.=1.76; P=0.04) DMRs. Changes related to maternal obesity detected at other loci were as follows: β-coefficient was +2.58 (s.e.=1.00; P=0.01) at the PLAGL1 DMR and -3.42 (s.e.=1.69; P=0.04) at the MEG3 DMR.We found altered methylation outcomes at multiple imprint regulatory regions in children born to obese parents, compared with children born to non-obese parents. In spite of the small sample size, our data suggest a preconceptional influence of parental life-style or overnutrition on the (re)programming of imprint marks during gametogenesis and early development. More specifically, the significant and independent association between paternal obesity and the offspring's methylation status suggests the susceptibility of the developing sperm for environmental insults. The acquired imprint instability may be carried onto the next generation and increase the risk for chronic diseases in adulthood.}, number={4}, journal={International Journal of Obesity}, publisher={Springer Science and Business Media LLC}, author={Soubry, A and Murphy, S K and Wang, F and Huang, Z and Vidal, A C and Fuemmeler, B F and Kurtzberg, J and Murtha, A and Jirtle, R L and Schildkraut, J M and et al.}, year={2013}, month={Oct}, pages={650–657} } @article{vidal_henry_murphy_oneko_nye_bartlett_overcash_huang_wang_mlay_et al._2013, title={PEG1/MEST and IGF2 DNA methylation in CIN and in cervical cancer}, volume={16}, ISSN={1699-048X 1699-3055}, url={http://dx.doi.org/10.1007/S12094-013-1067-4}, DOI={10.1007/S12094-013-1067-4}, abstractNote={Although most invasive cervical cancer (ICC) harbor <20 human papillomavirus (HPV) genotypes, use of HPV screening to predict ICC from HPV has low specificity, resulting in multiple and costly follow-up visits and overtreatment. We examined DNA methylation at regulatory regions of imprinted genes in relation to ICC and its precursor lesions to determine if methylation profiles are associated with progression of HPV-positive lesions to ICC.We enrolled 148 controls, 38 CIN and 48 ICC cases at Kilimanjaro Christian Medical Centre from 2008 to 2009. HPV was genotyped by linear array and HIV-1 serostatus was tested by two rapid HIV tests. DNA methylation was measured by bisulfite pyrosequencing at regions regulating eight imprinted domains. Logistic regression models were used to estimate odd ratios.After adjusting for age, HPV infection, parity, hormonal contraceptive use, and HIV-1 serostatus, a 10 % decrease in methylation levels at an intragenic region of IGF2 was associated with higher risk of ICC (OR 2.00, 95 % CI 1.14-3.44) and cervical intraepithelial neoplasia (CIN) (OR 1.51, 95 % CI 1.00-2.50). Methylation levels at the H19 DMR and PEG1/MEST were also associated with ICC risk (OR 1.51, 95 % CI 0.90-2.53, and OR 1.44, 95 % CI 0.90-2.35, respectively). Restricting analyses to women >30 years further strengthened these associations.While the small sample size limits inference, these findings show that altered DNA methylation at imprinted domains including IGF2/H19 and PEG1/MEST may mediate the association between HPV and ICC risk.}, number={3}, journal={Clinical and Translational Oncology}, publisher={Springer Science and Business Media LLC}, author={Vidal, A. C. and Henry, N. M. and Murphy, S. K. and Oneko, O. and Nye, M. and Bartlett, J. A. and Overcash, F. and Huang, Z. and Wang, F. and Mlay, P. and et al.}, year={2013}, month={Jun}, pages={266–272} } @article{grant_hoyo_akushevich_iversen_whitaker_marks_berchuck_schildkraut_2013, title={Vitamin D receptor (VDR) polymorphisms and risk of ovarian cancer in Caucasian and African American women}, volume={129}, ISSN={0090-8258}, url={http://dx.doi.org/10.1016/J.YGYNO.2012.12.027}, DOI={10.1016/J.YGYNO.2012.12.027}, abstractNote={Polymorphisms in the vitamin D receptor (VDR) gene have been shown in some studies to be associated with the risk of epithelial ovarian cancer (EOC) in Caucasian women. There are no published reports among African Americans.Case-control data from the North Carolina Ovarian Cancer Study were analyzed using logistic regression to determine the association between seven VDR polymorphisms and EOC in both Caucasians (513 cases, 532 controls) and African Americans (74 cases, 79 controls). In a larger sample of African-Americans (125 cases, 155 controls), we assessed associations between six SNPs in proximity of rs7975232.African American women who carried at least one minor allele of rs7975232 were at higher risk for invasive EOC controlling for age and admixture with an odds ratio (OR) for association under the log-additive model of 2.08 (95% confidence interval (CI)=1.19, 3.63, p=0.010). No association was observed between any of the VDR variants and EOC among Caucasians. A larger sample of African Americans revealed a nearly two-fold increased risk of invasive EOC associated with rs7305032, a SNP in proximity to rs7975232 (R(2)=0.369) with a log-additive OR of 1.87 (95% CI=1.20, 2.93, p=0.006).This is the first report showing VDR variants associated with ovarian cancer risk in African American women. A larger study of African American women is needed to confirm these findings. These results imply that vitamin D exposure is a possible modifiable risk factor of ovarian cancer among African Americans.}, number={1}, journal={Gynecologic Oncology}, publisher={Elsevier BV}, author={Grant, Delores J. and Hoyo, Cathrine and Akushevich, Lucy and Iversen, Edwin S. and Whitaker, Regina and Marks, Jeffrey and Berchuck, Andrew and Schildkraut, Joellen M.}, year={2013}, month={Apr}, pages={173–178} } @article{thomas_antonelli_bañez_gerber_hoyo_grant_demark-wahnefried_platz_calloway_eyoh_et al._2012, title={341 ANDROGENETIC ALOPECIA AT VARIOUS AGES AND PROSTATE CANCER RISK IN AN EQUAL ACCESS MULTIETHNIC CASE CONTROL SERIES OF VETERANS}, volume={187}, ISSN={0022-5347 1527-3792}, url={http://dx.doi.org/10.1016/j.juro.2012.02.402}, DOI={10.1016/j.juro.2012.02.402}, abstractNote={You have accessJournal of UrologyProstate Cancer: Epidemiology and Natural History II1 Apr 2012341 ANDROGENETIC ALOPECIA AT VARIOUS AGES AND PROSTATE CANCER RISK IN AN EQUAL ACCESS MULTIETHNIC CASE CONTROL SERIES OF VETERANS Jean-Alfred Thomas, Jodi A. Antonelli, Lionel L. Bañez, Leah Gerber, Cathrine Hoyo, Delores Grant, Wendy Demark-Wahnefried, Elizabeth Platz, Elizabeth Calloway, Enwono Eyoh, Kathleen Shuler, and Stephen J. Freedland Jean-Alfred ThomasJean-Alfred Thomas Durham, NC More articles by this author , Jodi A. AntonelliJodi A. Antonelli Durham, NC More articles by this author , Lionel L. BañezLionel L. Bañez Durham, NC More articles by this author , Leah GerberLeah Gerber Durham, NC More articles by this author , Cathrine HoyoCathrine Hoyo Durham, NC More articles by this author , Delores GrantDelores Grant Durham, NC More articles by this author , Wendy Demark-WahnefriedWendy Demark-Wahnefried Birmingham, AL More articles by this author , Elizabeth PlatzElizabeth Platz Balitmore, MD More articles by this author , Elizabeth CallowayElizabeth Calloway Durham, NC More articles by this author , Enwono EyohEnwono Eyoh Durham, NC More articles by this author , Kathleen ShulerKathleen Shuler Durham, NC More articles by this author , and Stephen J. FreedlandStephen J. Freedland Durham, NC More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2012.02.402AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Epidemiological data are conflicting regarding the association between androgenetic alopecia (AA) and prostate cancer (CaP). We examined the relationship between these two conditions. METHODS We performed a case-control study at a Veterans Affairs Hospital among 709 men: 312 healthy controls, 167 men with CaP, and 229 men without CaP on prostate biopsy. Participants were asked to self-describe hair patterns at ages 30, 40 and at study enrollment. We tested the association between hair pattern (overall, vertex or frontal) and CaP status using logistic regression analysis adjusting for multiple clinical features. Disease grade was similarly examined as a secondary outcome. RESULTS Relative to healthy controls, younger age of AA onset was significantly associated with increased CaP risk (p=0.008). Similar patterns were noted for frontal (p=0.004) and vertex balding (p=0.08). When compared to biopsy negative men, a similar pattern was seen with younger age of AA onset having higher risk for CaP, though this was not significant (p=0.08). Only younger age of AA onset for frontal (p=0.05) was associated with CaP vs. biopsy negative men. However, overall balding (yes/no) was with > 2-fold increase of high-grade disease (p<0.07). CONCLUSIONS In a multiethnic cohort, men reporting earlier AA onset were at increased CaP risk and suggestively had more aggressive disease. Contrary to other studies, frontal balding was the predominant pattern associated with elevated CaP risk. Further study is required to confirm these findings in a larger sample and to better understand the role of AA, androgens, and CaP biology. © 2012 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 187Issue 4SApril 2012Page: e139 Advertisement Copyright & Permissions© 2012 by American Urological Association Education and Research, Inc.MetricsAuthor Information Jean-Alfred Thomas Durham, NC More articles by this author Jodi A. Antonelli Durham, NC More articles by this author Lionel L. Bañez Durham, NC More articles by this author Leah Gerber Durham, NC More articles by this author Cathrine Hoyo Durham, NC More articles by this author Delores Grant Durham, NC More articles by this author Wendy Demark-Wahnefried Birmingham, AL More articles by this author Elizabeth Platz Balitmore, MD More articles by this author Elizabeth Calloway Durham, NC More articles by this author Enwono Eyoh Durham, NC More articles by this author Kathleen Shuler Durham, NC More articles by this author Stephen J. Freedland Durham, NC More articles by this author Expand All Advertisement Advertisement PDF DownloadLoading ...}, number={4S}, journal={Journal of Urology}, publisher={Ovid Technologies (Wolters Kluwer Health)}, author={Thomas, Jean-Alfred and Antonelli, Jodi A. and Bañez, Lionel L. and Gerber, Leah and Hoyo, Cathrine and Grant, Delores and Demark-Wahnefried, Wendy and Platz, Elizabeth and Calloway, Elizabeth and Eyoh, Enwono and et al.}, year={2012}, month={Apr} } @article{hoyo_fortner_murtha_schildkraut_soubry_demark-wahnefried_jirtle_kurtzberg_forman_overcash_et al._2012, title={Association of cord blood methylation fractions at imprinted insulin-like growth factor 2 (IGF2), plasma IGF2, and birth weight}, volume={23}, ISSN={0957-5243 1573-7225}, url={http://dx.doi.org/10.1007/S10552-012-9932-Y}, DOI={10.1007/S10552-012-9932-Y}, abstractNote={Altered methylation at Insulin-like Growth Factor 2 (IGF2) regulatory regions has previously been associated with obesity, and several malignancies including colon, esophageal, and prostate adenocarcinomas, presumably via changes in expression and/or loss of imprinting, but the functional significance of these DNA methylation marks have not been demonstrated in humans. We examined associations among DNA methylation at IGF2 differentially methylated regions (DMRs), circulating IGF2 protein concentrations in umbilical cord blood (UCB) and birth weight in newborns.Questionnaire data were obtained from 300 pregnant women recruited between 2005 and 2009. UCB DNA methylation was measured by bisulfite pyrosequencing. UCB plasma concentrations of soluble IGF2 were measured by ELISA assays. Generalized linear regression models were used to examine the relationship between DMR methylation and IGF2 levels.Lower IGF2 DMR methylation was associated with elevated plasma IGF2 protein concentrations (β = -9.87, p < 0.01); an association that was stronger in infants born to obese women (pre-pregnancy BMI > 30 kg/m(2), β = -20.21, p < 0.0001). Elevated IGF2 concentrations were associated with higher birth weight (p < 0.0001) after adjusting for maternal race/ethnicity, pre-pregnancy BMI, cigarette smoking, gestational diabetes, and infant sex. These patterns of association were not apparent at the H19 DMR.Our data suggest that variation in IGF2 DMR methylation is an important mechanism by which circulating IGF2 concentrations, a putative risk factor for obesity and cancers of the colon, esophagus, and prostate, are modulated; associations that may depend on pre-pregnancy obesity.}, number={4}, journal={Cancer Causes & Control}, publisher={Springer Science and Business Media LLC}, author={Hoyo, Cathrine and Fortner, Kimberly and Murtha, Amy P. and Schildkraut, Joellen M. and Soubry, Adelheid and Demark-Wahnefried, Wendy and Jirtle, Randy L. and Kurtzberg, Joanne and Forman, Michele R. and Overcash, Francine and et al.}, year={2012}, month={Mar}, pages={635–645} } @article{murphy_adigun_huang_overcash_wang_jirtle_schildkraut_murtha_iversen_hoyo_2012, title={Gender-specific methylation differences in relation to prenatal exposure to cigarette smoke}, volume={494}, ISSN={0378-1119}, url={http://dx.doi.org/10.1016/j.gene.2011.11.062}, DOI={10.1016/j.gene.2011.11.062}, abstractNote={Epigenetic alterations may mechanistically explain the developmental origins of adult disease, namely the hypothesis that many complex adult chronic diseases originate as a result of conditions encountered in utero. If true, epigenetically regulated imprinted genes, critical to normal growth and development, may partially mediate these outcomes. We determined the influence of in utero exposure to cigarette smoking on methylation at two differentially methylated regions (DMRs) regulating Insulin-like Growth Factor 2 (IGF2) and H19, and how this might relate to birth weight of infants born to 418 pregnant women. Smoking status was ascertained through self-report and medical records. Bisulfite pyrosequencing was used to measure methylation in umbilical cord blood DNAs. Least squares DNA methylation means at each DMR and birth weight were compared between infants of smokers and non-smokers, using generalized linear models. While there were no significant differences at the H19 DMR, infants born to smokers had higher methylation at the IGF2 DMR than those born to never smokers or those who quit during pregnancy (49.5%, SD = 8.0 versus 46.6%, SD = 5.6 and 45.8%, SD = 6.3, respectively; p = 0.0002). The smoking-related increase in methylation was most pronounced in male offspring (p for sex interaction = 0.03), for whom approximately 20% of smoking-related low birth weight was mediated by DNA methylation at the IGF2 DMR. Our findings suggest that IGF2 DMR plasticity is an important mechanism by which in utero adjustments to environmental toxicants are conferred. Larger studies to replicate these findings are required.}, number={1}, journal={Gene}, publisher={Elsevier BV}, author={Murphy, Susan K. and Adigun, Abayomi and Huang, Zhiqing and Overcash, Francine and Wang, Frances and Jirtle, Randy L. and Schildkraut, Joellen M. and Murtha, Amy P. and Iversen, Edwin S. and Hoyo, Cathrine}, year={2012}, month={Feb}, pages={36–43} } @article{keku_vidal_oliver_hoyo_hall_omofoye_mcdoom_worley_galanko_sandler_et al._2012, title={Genetic variants in IGF-I, IGF-II, IGFBP-3, and adiponectin genes and colon cancer risk in African Americans and Whites}, volume={23}, ISSN={0957-5243 1573-7225}, url={http://dx.doi.org/10.1007/S10552-012-9981-2}, DOI={10.1007/S10552-012-9981-2}, abstractNote={Evaluating genetic susceptibility may clarify effects of known environmental factors and also identify individuals at high risk. We evaluated the association of four insulin-related pathway gene polymorphisms in insulin-like growth factor-1 (IGF-I) (CA)( n ) repeat, insulin-like growth factor-2 (IGF-II) (rs680), insulin-like growth factor-binding protein-3 (IGFBP-3) (rs2854744), and adiponectin (APM1 rs1501299) with colon cancer risk, as well as relationships with circulating IGF-I, IGF-II, IGFBP-3, and C-peptide in a population-based study.Participants were African Americans (231 cases and 306 controls) and Whites (297 cases, 530 controls). Consenting subjects provided blood specimens and lifestyle/diet information. Genotyping for all genes except IGF-I was performed by the 5'-exonuclease (Taqman) assay. The IGF-I (CA)(n) repeat was assayed by PCR and fragment analysis. Circulating proteins were measured by enzyme immunoassays. Odds ratios (ORs) and 95 % confidence intervals (CIs) were calculated by logistic regression.The IGF-I (CA)( 19 ) repeat was higher in White controls (50 %) than African American controls (31 %). Whites homozygous for the IGF-I (CA)(19) repeat had a nearly twofold increase in risk of colon cancer (OR = 1.77; 95 % CI = 1.15-2.73), but not African Americans (OR = 0.73, 95 % CI 0.50-1.51). We observed an inverse association between the IGF-II Apa1 A-variant and colon cancer risk (OR = 0.49, 95 % CI 0.28-0.88) in Whites only. Carrying the IGFBP-3 variant alleles was associated with lower IGFBP-3 protein levels, a difference most pronounced in Whites (p-trend <0.05).These results support an association between insulin pathway-related genes and elevated colon cancer risk in Whites but not in African Americans.}, number={7}, journal={Cancer Causes & Control}, publisher={Springer Science and Business Media LLC}, author={Keku, Temitope O. and Vidal, Adriana and Oliver, Shannon and Hoyo, Catherine and Hall, Ingrid J. and Omofoye, Oluwaseun and McDoom, Maya and Worley, Kendra and Galanko, Joseph and Sandler, Robert S. and et al.}, year={2012}, month={May}, pages={1127–1138} } @article{perkins_murphy_murtha_schildkraut_jirtle_demark-wahnefried_forman_kurtzberg_overcash_huang_et al._2012, title={Insulin-Like Growth Factor 2/H19 Methylation at Birth and Risk of Overweight and Obesity in Children}, volume={161}, ISSN={0022-3476}, url={http://dx.doi.org/10.1016/j.jpeds.2012.01.015}, DOI={10.1016/j.jpeds.2012.01.015}, abstractNote={To determine whether aberrant DNA methylation at differentially methylated regions (DMRs) regulating insulin-like growth factor 2 (IGF2) expression in umbilical cord blood is associated with overweight or obesity in a multiethnic cohort.Umbilical cord blood leukocytes of 204 infants born between 2005 and 2009 in Durham, North Carolina, were analyzed for DNA methylation at two IGF2 DMRs by using pyrosequencing. Anthropometric and feeding data were collected at age 1 year. Methylation differences were compared between children >85th percentile of the Centers for Disease Control and Prevention growth charts weight-for-age (WFA) and children ≤ 85th percentile of WFA at 1 year by using generalized linear models, adjusting for post-natal caloric intake, maternal cigarette smoking, and race/ethnicity.The methylation percentages at the H19 imprint center DMR was higher in infants with WFA >85th percentile (62.7%; 95% CI, 59.9%-65.5%) than in infants with WFA ≤ 85th percentile (59.3%; 95% CI, 58.2%-60.3%; P = .02). At the intragenic IGF2 DMR, methylation levels were comparable between infants with WFA ≤ 85th percentile and infants with WFA >85th percentile.Our findings suggest that IGF2 plasticity may be mechanistically important in early childhood overweight or obese status. If confirmed in larger studies, these findings suggest aberrant DNA methylation at sequences regulating imprinted genes may be useful identifiers of children at risk for the development of early obesity.}, number={1}, journal={The Journal of Pediatrics}, publisher={Elsevier BV}, author={Perkins, Ellen and Murphy, Susan K. and Murtha, Amy P. and Schildkraut, Joellen and Jirtle, Randy L. and Demark-Wahnefried, Wendy and Forman, Michele R. and Kurtzberg, Joanne and Overcash, Francine and Huang, Zhiqing and et al.}, year={2012}, month={Jul}, pages={31–39} } @article{masko_moreira_bañez_hoyo_grant_calloway_shuler_newman_gaines_taylor_et al._2011, title={1613 GENETIC VARIATION IN OBESITY-RELATED GENES ADBR2, ADBR3, GHRL, HSD11B1, AND SHC1 AND RISK OF PROSTATE CANCER: A VA CASE-CONTROL STUDY}, volume={185}, ISSN={0022-5347 1527-3792}, url={http://dx.doi.org/10.1016/j.juro.2011.02.1721}, DOI={10.1016/j.juro.2011.02.1721}, abstractNote={You have accessJournal of UrologyProstate Cancer: Basic Research1 Apr 20111613 GENETIC VARIATION IN OBESITY-RELATED GENES ADBR2, ADBR3, GHRL, HSD11B1, AND SHC1 AND RISK OF PROSTATE CANCER: A VA CASE-CONTROL STUDY Elizabeth M. Masko, Daniel M. Moreira, Lionel L. Bañez, Cathrine Hoyo, Delores J. Grant, Elizabeth E. Calloway, Kathleen H. Shuler, Kathryn A. Newman, Alexis R. Gaines, Loretta A. Taylor, Cary N. Robertson, and Stephen J. Freedland Elizabeth M. MaskoElizabeth M. Masko Durham, NC More articles by this author , Daniel M. MoreiraDaniel M. Moreira New Hyde Park, NY More articles by this author , Lionel L. BañezLionel L. Bañez Durham, NC More articles by this author , Cathrine HoyoCathrine Hoyo Durham, NC More articles by this author , Delores J. GrantDelores J. Grant Durham, NC More articles by this author , Elizabeth E. CallowayElizabeth E. Calloway Durham, NC More articles by this author , Kathleen H. ShulerKathleen H. Shuler Durham, NC More articles by this author , Kathryn A. NewmanKathryn A. Newman Durham, NC More articles by this author , Alexis R. GainesAlexis R. Gaines Durham, NC More articles by this author , Loretta A. TaylorLoretta A. Taylor Durham, NC More articles by this author , Cary N. RobertsonCary N. Robertson Durham, NC More articles by this author , and Stephen J. FreedlandStephen J. Freedland Durham, NC More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2011.02.1721AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Single nucleotide polymorphisms (SNPs) are single nucleotide variations that occur within alleles among individuals. It is believed that SNPs may predispose a person to diseases such as obesity or cancer. One study showed that SNPs within genes linked with obesity were also associated with breast cancer risk. As prostate cancer (PC) mortality is linked with obesity, we determined if SNPs within 5 obesity-related genes were also linked to PC risk in a similar manner to the breast cancer study. METHODS A total of 53 SNPs were tagged in the genes ADBR2, ADBR3, GHRL, HSD11B1, and SHC1 using the program HAPMAP. DNA collected from 216 subjects (108 incident cases, 108 “healthy” controls) from the Durham VA Hospital were then genotyped for these SNPs. Cases and controls were frequency matched on age and BMI. Logistic regression models were used to determine the risk of obesity (BMI >30 kg/m2) and PC (and high-grade defined as Gleason >7 vs. low-grade/control) for each SNP, adjusting for age and race. RESULTS In our study population, 83 men were Caucasian and 133 African American. There was no significant differences in age (p=0.18), race (p=0.96), and BMI (p=0.12) for cases and controls. Among the 53 SNPs genotyped, 5 SNPs in ADRB2, ADRB3, and SHC1 were associated with an increased risk of PC (OR 1.88–2.21; p=0.01–0.04), particularly high-grade disease (OR 2.50–3.26; p=0.0004–0.05). Another 4 SNPs in ADRB2 and HSD11B1 were associated with a decreased risk of PC (p=0.01–0.05). A total of 7 SNPs were associated with an increased risk of obesity (p=0.004–0.02). CONCLUSIONS In this small pilot study, we found 14 of the 53 analyzed single SNPs in genes previously linked with obesity that were associated with PC risk, both positively and negatively at an alpha of <0.05. This is more than the 3 SNPs that would be predicted based upon random chance. Future studies will validate these results in an independent cohort, with the hope of further confirming SNPs that may be used for personalized medicine as well as providing a genetic link between obesity and PC. © 2011 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 185Issue 4SApril 2011Page: e647 Advertisement Copyright & Permissions© 2011 by American Urological Association Education and Research, Inc.MetricsAuthor Information Elizabeth M. Masko Durham, NC More articles by this author Daniel M. Moreira New Hyde Park, NY More articles by this author Lionel L. Bañez Durham, NC More articles by this author Cathrine Hoyo Durham, NC More articles by this author Delores J. Grant Durham, NC More articles by this author Elizabeth E. Calloway Durham, NC More articles by this author Kathleen H. Shuler Durham, NC More articles by this author Kathryn A. Newman Durham, NC More articles by this author Alexis R. Gaines Durham, NC More articles by this author Loretta A. Taylor Durham, NC More articles by this author Cary N. Robertson Durham, NC More articles by this author Stephen J. Freedland Durham, NC More articles by this author Expand All Advertisement Advertisement PDF DownloadLoading ...}, number={4S}, journal={Journal of Urology}, publisher={Ovid Technologies (Wolters Kluwer Health)}, author={Masko, Elizabeth M. and Moreira, Daniel M. and Bañez, Lionel L. and Hoyo, Cathrine and Grant, Delores J. and Calloway, Elizabeth E. and Shuler, Kathleen H. and Newman, Kathryn A. and Gaines, Alexis R. and Taylor, Loretta A. and et al.}, year={2011}, month={Apr} } @article{bañez_hoyo_masko_calloway_shuler_newman_gaines_freedland_robertson_2011, title={605 COMBINATION OF ADH GENE POLYMORPHISM AND ALCOHOL CONSUMPTION CONSTITUTES A NOVEL PROSTATE CANCER RISK FACTOR IN AFRICAN-AMERICAN MEN}, volume={185}, ISSN={0022-5347 1527-3792}, url={http://dx.doi.org/10.1016/j.juro.2011.02.1458}, DOI={10.1016/j.juro.2011.02.1458}, abstractNote={You have accessJournal of UrologyProstate Cancer: Basic Research1 Apr 2011605 COMBINATION OF ADH GENE POLYMORPHISM AND ALCOHOL CONSUMPTION CONSTITUTES A NOVEL PROSTATE CANCER RISK FACTOR IN AFRICAN-AMERICAN MEN Lionel L. Bañez, Cathrine Hoyo, Elizabeth M. Masko, Elizabeth E. Calloway, Kathleen H. Shuler, Kathryn A. Newman, Alexis R. Gaines, Stephen J. Freedland, and Cary N. Robertson Lionel L. BañezLionel L. Bañez Durham, NC More articles by this author , Cathrine HoyoCathrine Hoyo Durham, NC More articles by this author , Elizabeth M. MaskoElizabeth M. Masko Durham, NC More articles by this author , Elizabeth E. CallowayElizabeth E. Calloway Durham, NC More articles by this author , Kathleen H. ShulerKathleen H. Shuler Durham, NC More articles by this author , Kathryn A. NewmanKathryn A. Newman Durham, NC More articles by this author , Alexis R. GainesAlexis R. Gaines Durham, NC More articles by this author , Stephen J. FreedlandStephen J. Freedland Durham, NC More articles by this author , and Cary N. RobertsonCary N. Robertson Durham, NC More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2011.02.1458AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES African-American men (AAM) are at higher risk for prostate cancer (PC) vs. Caucasian men (CM). The cause is likely multi-factorial. Though alcohol intake as a PC risk factor in the overall population is controversial, we recently reported that, among men undergoing prostate biopsy, alcohol intake was associated with increased PC risk only among AAM. Polymorphisms of the alcohol dehydrogenase (ADH) gene, that lead to bodily accumulation of acetaldehyde - a carcinogen, occur more frequently in AAM. Whether these alleles interact with alcohol exposure to promote PC development is unknown. METHODS DNA and alcohol intake surveys were obtained from 347 men from the Durham VA Hospital who underwent prostate biopsy (n=199) or were hospital-based controls (n=148 with no indication for biopsy) from 2007 to 2010. The DNA was genotyped for ADH1B*3 and dichotomized into carriers of the common allele (ADH1B*3-; C/C) and the variant allele (ADH1B*3+; C/T or T/T). Alcohol intake was dichotomized into non-drinker and alcohol drinker. Two separate logistic regression models, adjusting for clinical covariates, were conducted: 1) Only among men who underwent a biopsy; 2) Comparing men with cancer on biopsy to the controls. RESULTS A total of 60 (13%) men were heterozygous and 11 (2%) were homozygous for ADH1B*3. Nearly all ADH1B*3+ subjects were AAM (n=69; 97%) with 35% of AAM carrying the variant allele. ADH1B*3+ alcohol drinkers were ∼4 times more likely to have a positive biopsy than ADH1B*3- non-drinkers (OR=3.7, 95%CI=1.0–13.3). In crude analysis comparing biopsy+ men to controls, ADH1B*3+ alcohol drinkers were 5 times more likely to have PC than ADH1B*3- non-drinkers. There was a trend for increased PC risk among ADH1B*3+ alcohol drinkers in multivariate analyses which did not reach statistical significance (p=0.11). In all models, PC risk for ADH1B*3+ non-drinkers and ADH1B*3- alcohol drinkers were not different from ADH1B*3- non-drinkers. CONCLUSIONS Our preliminary findings suggest the ADH1B*3 variant allele and alcohol intake is a novel gene-environment interaction for PC risk, nearly unique to AAM. If confirmed, this gene-environment interaction may help explain increased PC risk in AAM who consume alcohol, while no effect is seen in CM. Table 1. Odds ratios (OR) and 95% confidence intervals (CI) for prostate cancer among risk groups based on ADH1B*3 genotype and alcohol intake Biopsy(+) vs. Biopsy(-) Biopsy(+) vs. Biopsy(-) Biopsy(+) vs. Controls Biopsy(+) vs. Controls Crude Adjusted⁎ Crude Adjusted⁎⁎ ADH1B*3 Alcohol OR (95% CI) p OR (95% CI) p OR (95% CI) p OR (95% CI) p (-) (-) Ref Ref Ref Ref (+) (+) 4.36(1.36-13.94) 0.02 3.67(1.02-13.28) 0.047 5.21(1.64-16.61) 0.005 3.08(0.77-12.25) 0.11 (+) (-) 1.24(0.47-3.31) 0.67 1.01(0.34-3.05) 0.98 1.60(0.60-4.29) 0.35 1.77(0.51-6.15) 0.37 (-) (+) 1.70(0.89-3.24) 0.10 1.85(0.91-3.73) 0.09 1.46(0.89-3.60) 0.22 1.57(0.75-3.38) 0.23 ⁎ adjusted for age, race, PSA, body mass index and year of biopsy; ⁎⁎ adjusted for age, race, BMI and year of enrollment © 2011 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 185Issue 4SApril 2011Page: e244 Advertisement Copyright & Permissions© 2011 by American Urological Association Education and Research, Inc.MetricsAuthor Information Lionel L. Bañez Durham, NC More articles by this author Cathrine Hoyo Durham, NC More articles by this author Elizabeth M. Masko Durham, NC More articles by this author Elizabeth E. Calloway Durham, NC More articles by this author Kathleen H. Shuler Durham, NC More articles by this author Kathryn A. Newman Durham, NC More articles by this author Alexis R. Gaines Durham, NC More articles by this author Stephen J. Freedland Durham, NC More articles by this author Cary N. Robertson Durham, NC More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...}, number={4S}, journal={Journal of Urology}, publisher={Ovid Technologies (Wolters Kluwer Health)}, author={Bañez, Lionel L. and Hoyo, Cathrine and Masko, Elizabeth M. and Calloway, Elizabeth E. and Shuler, Kathleen H. and Newman, Kathryn A. and Gaines, Alexis R. and Freedland, Stephen J. and Robertson, Cary N.}, year={2011}, month={Apr} } @article{williams_whitley_hoyo_grant_iraggi_newman_gerber_taylor_mckeever_freedland_2011, title={A high ratio of dietary n-6/n-3 polyunsaturated fatty acids is associated with increased risk of prostate cancer}, volume={31}, ISSN={0271-5317}, url={http://dx.doi.org/10.1016/j.nutres.2011.01.002}, DOI={10.1016/j.nutres.2011.01.002}, abstractNote={Experimental studies suggest omega-3 (n-3) polyunsaturated fatty acids (PUFA) suppress and n-6 PUFA promote prostate tumor carcinogenesis. Epidemiologic evidence remains inconclusive. The objectives of this study were to examine the association between n-3 and n-6 PUFA and prostate cancer risk and determine if these associations differ by race or disease aggressiveness. We hypothesize that high intakes of n-3 and n-6 PUFA will be associated with lower and higher prostate cancer risk, respectively. A case-control study comprising 79 prostate cancer cases and 187 controls was conducted at the Durham VA Medical Center. Diet was assessed using a food frequency questionnaire. Logistic regression analyses were used to obtain odds ratios (ORs) and 95% confidence intervals (95% CI) for the associations between n-3 and n-6 PUFA intakes, the dietary ratio of n-6/n-3 fatty acids, and prostate cancer risk. Our results showed no significant associations between specific n-3 or n-6 PUFA intakes and prostate cancer risk. The highest dietary ratio of n-6/n-3 was significantly associated with elevated risk of high-grade (OR, 3.55; 95% CI, 1.18-10.69; P(trend) = 0.03), but not low-grade prostate cancer (OR, 0.95; 95% CI, 0.43-2.17). In race-specific analyses, an increasing dietary ratio of n-6/n-3 fatty acids correlated with higher prostate cancer risk among white men (P(trend) = 0.05), but not black men. In conclusion, our findings suggest that a high dietary ratio of n-6/n-3 fatty acids may increase the risk of overall prostate cancer among white men and possibly increase the risk of high-grade prostate cancer among all men.}, number={1}, journal={Nutrition Research}, publisher={Elsevier BV}, author={Williams, Christina D. and Whitley, Brian M. and Hoyo, Cathrine and Grant, Delores J. and Iraggi, Jared D. and Newman, Kathryn A. and Gerber, Leah and Taylor, Loretta A. and McKeever, Madeline G. and Freedland, Stephen J.}, year={2011}, month={Jan}, pages={1–8} } @article{moreira_anderson_gerber_thomas_bañez_mckeever_hoyo_grant_jayachandran_freedland_2011, title={The association of diabetes mellitus and high-grade prostate cancer in a multiethnic biopsy series}, volume={22}, ISSN={0957-5243 1573-7225}, url={http://dx.doi.org/10.1007/s10552-011-9770-3}, DOI={10.1007/s10552-011-9770-3}, abstractNote={{"Label"=>"OBJECTIVE", "NlmCategory"=>"OBJECTIVE"} To analyze the association of diabetes mellitus (DM) with risk of prostate cancer and cancer grade among men undergoing prostate biopsy and to analyze how obesity and race modify these associations. {"Label"=>"MATERIALS AND METHODS", "NlmCategory"=>"METHODS"} Retrospective analysis of 998 men from the Durham VA undergoing first prostate biopsy between 2001 and 2009 with complete data available. History of DM was determined by chart review. Patients' characteristics at biopsy were analyzed with chi-square and ranksum. Multivariable analyses of DM and risk of cancer and cancer grade were done using logistic regression adjusting for PSA, body mass index, race, age, year, and digital rectal exam. {"Label"=>"RESULTS", "NlmCategory"=>"RESULTS"} At biopsy, 284 (28%) men had DM. DM was associated with African American (AAM; p = 0.010) and higher BMI (p < 0.001). DM was not associated with prostate cancer risk on either bivariate (p = 0.600) or multivariate analysis (p = 0.485). Similar results were found after stratification by race and obesity. In multivariable analysis, DM was associated with greater risk of high-grade disease (RR = 2.13, p = 0.024). The association was stronger among obese men (RR = 3.84, p = 0.020) and null in non-obese subjects (RR = 1.39, p = 0.460). After further stratification by race, DM was associated with high-grade disease only in obese Caucasian men (CM; RR = 5.81, p = 0.025) but not in obese AAM. DM was not associated with risk of low-grade disease in all men together or after stratification by obesity or race. {"Label"=>"CONCLUSION", "NlmCategory"=>"CONCLUSIONS"} History of DM was associated with greater risk of high-grade disease. The association was strongest among obese CM suggesting the effect of DM on high-grade prostate cancer is modified by race and obesity.}, number={7}, journal={Cancer Causes & Control}, publisher={Springer Science and Business Media LLC}, author={Moreira, Daniel M. and Anderson, Tiffany and Gerber, Leah and Thomas, Jean-Alfred and Bañez, Lionel L. and McKeever, Madeline G. and Hoyo, Cathrine and Grant, Delores and Jayachandran, Jayakrishnan and Freedland, Stephen J.}, year={2011}, month={May}, pages={977–983} } @article{fortner_murtha_hoyo_overcash_huang_schildkraut_kurtzberg_jirtle_forman_murphy_2009, title={70: Epigenetic orchestration of circulating insulin-like growth factor-2 levels in cord blood}, volume={201}, ISSN={0002-9378}, url={http://dx.doi.org/10.1016/j.ajog.2009.10.085}, DOI={10.1016/j.ajog.2009.10.085}, number={6}, journal={American Journal of Obstetrics and Gynecology}, publisher={Elsevier BV}, author={Fortner, Kimberly and Murtha, Amy and Hoyo, Cathrine and Overcash, Francine and Huang, Zhiquing and Schildkraut, Joellen and Kurtzberg, Joanne and Jirtle, Randy and Forman, Michele and Murphy, Susan}, year={2009}, month={Dec}, pages={S39} } @article{antonelli_jones_bañez_thomas_anderson_taylor_gerber_anderson_hoyo_grant_et al._2009, title={Exercise and Prostate Cancer Risk in a Cohort of Veterans Undergoing Prostate Needle Biopsy}, volume={182}, ISSN={0022-5347 1527-3792}, url={http://dx.doi.org/10.1016/j.juro.2009.07.028}, DOI={10.1016/j.juro.2009.07.028}, abstractNote={No AccessJournal of UrologyAdult Urology1 Nov 2009Exercise and Prostate Cancer Risk in a Cohort of Veterans Undergoing Prostate Needle Biopsyis accompanied byCan Men Reduce the Risk of Prostate Cancer Through Lifestyle Changes? Jodi A. Antonelli, Lee W. Jones, Lionel L. Bañez, Jean-Alfred Thomas, Kelly Anderson, Loretta A. Taylor, Leah Gerber, Tiffany Anderson, Catherine Hoyo, Delores Grant, and Stephen J. Freedland Jodi A. AntonelliJodi A. Antonelli Duke Prostate Center, Division of Urologic Surgery, Duke University Medical Center, Durham, North Carolina Section of Urology, Department of Surgery, Durham Veterans Affairs Medical Center, Durham, North Carolina , Lee W. JonesLee W. Jones Robert Preston Tisch Brain Tumor Center, Duke University Medical Center, Durham, North Carolina , Lionel L. BañezLionel L. Bañez Duke Prostate Center, Division of Urologic Surgery, Duke University Medical Center, Durham, North Carolina Section of Urology, Department of Surgery, Durham Veterans Affairs Medical Center, Durham, North Carolina , Jean-Alfred ThomasJean-Alfred Thomas Duke Prostate Center, Division of Urologic Surgery, Duke University Medical Center, Durham, North Carolina Section of Urology, Department of Surgery, Durham Veterans Affairs Medical Center, Durham, North Carolina , Kelly AndersonKelly Anderson Duke Prostate Center, Division of Urologic Surgery, Duke University Medical Center, Durham, North Carolina Section of Urology, Department of Surgery, Durham Veterans Affairs Medical Center, Durham, North Carolina , Loretta A. TaylorLoretta A. Taylor Duke Prostate Center, Division of Urologic Surgery, Duke University Medical Center, Durham, North Carolina Section of Urology, Department of Surgery, Durham Veterans Affairs Medical Center, Durham, North Carolina , Leah GerberLeah Gerber Duke Prostate Center, Division of Urologic Surgery, Duke University Medical Center, Durham, North Carolina Section of Urology, Department of Surgery, Durham Veterans Affairs Medical Center, Durham, North Carolina , Tiffany AndersonTiffany Anderson Section of Urology, Department of Surgery, Durham Veterans Affairs Medical Center, Durham, North Carolina JLC-Biomedical/Biotechnology Research Institute, Cancer Research Program, North Carolina Central University, Durham, North Carolina , Catherine HoyoCatherine Hoyo Department of Surgery, Department of Community and Family Medicine, Duke University Medical Center, Durham, North Carolina , Delores GrantDelores Grant JLC-Biomedical/Biotechnology Research Institute, Cancer Research Program, North Carolina Central University, Durham, North Carolina , and Stephen J. FreedlandStephen J. Freedland Duke Prostate Center, Division of Urologic Surgery, Duke University Medical Center, Durham, North Carolina Department of Pathology, Duke University Medical Center, Durham, North Carolina Section of Urology, Department of Surgery, Durham Veterans Affairs Medical Center, Durham, North Carolina View All Author Informationhttps://doi.org/10.1016/j.juro.2009.07.028AboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract Purpose: Epidemiological and molecular evidence suggest potential associations between exercise and prostate cancer risk reduction. We further characterized this relationship by examining exercise and cancer risk among men undergoing prostate needle biopsy. Materials and Methods: A total of 190 men who underwent prostate biopsy at the Durham Veterans Affairs Medical Center completed a questionnaire on current exercise behavior. Participants were asked average frequency of mild, moderate and strenuous intensity exercise in a typical week, as well as average duration as assessed by the Godin Leisure Time Exercise Questionnaire. Total current exercise was calculated in terms of metabolic equivalent task hours per week. Primary outcome measures were prostate biopsy result and Gleason sum. Results: After adjusting for age, race, body mass index, prostate specific antigen, digital rectal examination, family history, previous prostate biopsy and comorbidity score, men who reported 9 or more metabolic equivalent task hours per week of exercise were significantly less likely to have cancer on biopsy (OR 0.35, CI 0.17–0.75, p = 0.007). Furthermore, among men with malignant biopsy results, reporting moderate exercise (3 to 8.9 metabolic equivalent task hours weekly) was associated with a lower risk of high grade disease (Gleason 7 or greater, OR 0.14, CI 0.02–0.94, p = 0.04). Conclusions: To our knowledge these results provide the first evidence of an association between exercise and prostate cancer risk as well as grade at diagnosis in men scheduled to undergo prostate biopsy. Specifically moderate exercise was associated with a lower risk of prostate cancer and in men with cancer, lower grade disease. Further investigation using an objective measure of exercise in a larger sample size is required to confirm these findings. References 1 : A mechanism to explain how regular exercise might reduce the risk for clinical prostate cancer. Eur J Cancer Prev2007; 16: 415. Google Scholar 2 : Exercise alters the IGF axis in vivo and increases p53 protein in prostate tumor cells in vitro. J Appl Physiol2004; 96: 450. Google Scholar 3 : Intensive lifestyle changes may affect the progression of prostate cancer. J Urol2005; 174: 1065. Link, Google Scholar 4 : Exercise and hormesis: activation of cellular antioxidant signaling pathway. Ann N Y Acad Sci2006; 1067: 425. 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Antonelli Duke Prostate Center, Division of Urologic Surgery, Duke University Medical Center, Durham, North Carolina Section of Urology, Department of Surgery, Durham Veterans Affairs Medical Center, Durham, North Carolina More articles by this author Lee W. Jones Robert Preston Tisch Brain Tumor Center, Duke University Medical Center, Durham, North Carolina More articles by this author Lionel L. Bañez Duke Prostate Center, Division of Urologic Surgery, Duke University Medical Center, Durham, North Carolina Section of Urology, Department of Surgery, Durham Veterans Affairs Medical Center, Durham, North Carolina More articles by this author Jean-Alfred Thomas Duke Prostate Center, Division of Urologic Surgery, Duke University Medical Center, Durham, North Carolina Section of Urology, Department of Surgery, Durham Veterans Affairs Medical Center, Durham, North Carolina More articles by this author Kelly Anderson Duke Prostate Center, Division of Urologic Surgery, Duke University Medical Center, Durham, North Carolina Section of Urology, Department of Surgery, Durham Veterans Affairs Medical Center, Durham, North Carolina More articles by this author Loretta A. Taylor Duke Prostate Center, Division of Urologic Surgery, Duke University Medical Center, Durham, North Carolina Section of Urology, Department of Surgery, Durham Veterans Affairs Medical Center, Durham, North Carolina More articles by this author Leah Gerber Duke Prostate Center, Division of Urologic Surgery, Duke University Medical Center, Durham, North Carolina Section of Urology, Department of Surgery, Durham Veterans Affairs Medical Center, Durham, North Carolina More articles by this author Tiffany Anderson Section of Urology, Department of Surgery, Durham Veterans Affairs Medical Center, Durham, North Carolina JLC-Biomedical/Biotechnology Research Institute, Cancer Research Program, North Carolina Central University, Durham, North Carolina More articles by this author Catherine Hoyo Department of Surgery, Department of Community and Family Medicine, Duke University Medical Center, Durham, North Carolina More articles by this author Delores Grant JLC-Biomedical/Biotechnology Research Institute, Cancer Research Program, North Carolina Central University, Durham, North Carolina More articles by this author Stephen J. Freedland Duke Prostate Center, Division of Urologic Surgery, Duke University Medical Center, Durham, North Carolina Department of Pathology, Duke University Medical Center, Durham, North Carolina Section of Urology, Department of Surgery, Durham Veterans Affairs Medical Center, Durham, North Carolina More articles by this author Expand All Advertisement PDF downloadLoading ...}, number={5}, journal={Journal of Urology}, publisher={Ovid Technologies (Wolters Kluwer Health)}, author={Antonelli, Jodi A. and Jones, Lee W. and Bañez, Lionel L. and Thomas, Jean-Alfred and Anderson, Kelly and Taylor, Loretta A. and Gerber, Leah and Anderson, Tiffany and Hoyo, Catherine and Grant, Delores and et al.}, year={2009}, month={Nov}, pages={2226–2231} } @article{hoyo_schildkraut_murphy_chow_vaughan_risch_marks_jirtle_calingeart_mayne_et al._2009, title={IGF2Rpolymorphisms and risk of esophageal and gastric adenocarcinomas}, volume={125}, ISSN={0020-7136 1097-0215}, url={http://dx.doi.org/10.1002/ijc.24623}, DOI={10.1002/ijc.24623}, abstractNote={Abstract}, number={11}, journal={International Journal of Cancer}, publisher={Wiley}, author={Hoyo, Cathrine and Schildkraut, Joellen M. and Murphy, Susan K. and Chow, Wong-Ho and Vaughan, Thomas L. and Risch, Harvey and Marks, Jeffrey R. and Jirtle, Randy L. and Calingeart, Brian and Mayne, Susan and et al.}, year={2009}, month={Dec}, pages={2673–2678} } @article{hoyo_grubber_demark-wahnefried_lobaugh_jeffreys_grambow_marks_keku_walther_schildkraut_2009, title={Predictors of Variation in Serum IGFI and IGFBP3 Levels in Healthy African American and White Men}, volume={101}, ISSN={0027-9684}, url={http://dx.doi.org/10.1016/S0027-9684(15)30981-0}, DOI={10.1016/S0027-9684(15)30981-0}, abstractNote={Individual variation in circulating insulinlike growth factor-1 (IGF1) and its major binding protein, insulinlike growth factor binding protein-3 (IGFBP3), have been etiologically linked to several chronic diseases, including some cancers. Factors associated with variation in circulating levels of these peptide hormones remain unclear.Multiple linear regression models were used to determine the extent to which sociodemographic characteristics, lifestyle factors, personal and family history of chronic disease, and common genetic variants, the (CA)n repeat polymorphism in the IGF1 promoter and the IGFBP3-202 A/C polymorphism (rs2854744) predict variation in IGF1 or IGFBP3 serum levels in 33 otherwise healthy African American and 37 white males recruited from Durham Veterans Administration Medical Center.Predictors of serum IGF1, IGFBP3, and the IGF1:IGFBP3 molar ratio varied by race. In African Americans, 17% and 28% of the variation in serum IGF1 and the IGF1:IGFBP3 molar ratio, were explained by cigarette smoking and carrying the IGF1 (CA)19 repeat allele, respectively. Not carrying at least 1 IGF1 (CA)19 repeat allele and a high body mass index explained 8% and 14%, respectively, of the variation IGFBP3 levels. These factors did not predict variation of these peptides in whites.If successfully replicated in larger studies, these findings would add to recent evidence, suggesting known genetic and lifestyle chronic disease risk factors influence IGF1 and IGFBP3 circulating levels differently in African Americans and whites.}, number={7}, journal={Journal of the National Medical Association}, publisher={Elsevier BV}, author={Hoyo, Cathrine and Grubber, Janet and Demark-Wahnefried, Wendy and Lobaugh, Bruce and Jeffreys, Amy S. and Grambow, Steven C. and Marks, Jeffrey R. and Keku, Temitope O. and Walther, Phillip J. and Schildkraut, Joellen M.}, year={2009}, month={Jul}, pages={711–716} } @article{hoyo_yarnall_fortney_2007, title={Short birth intervals and uterine cervical cancer risk in Jamaican women}, volume={98}, ISSN={0020-7292}, url={http://dx.doi.org/10.1016/j.ijgo.2007.04.010}, DOI={10.1016/j.ijgo.2007.04.010}, abstractNote={International Journal of Gynecology & ObstetricsVolume 98, Issue 1 p. 56-57 Brief communications Short birth intervals and uterine cervical cancer risk in Jamaican women C. Hoyo, Corresponding Author C. Hoyo cathrine.hoyo@duke.edu Duke University Medical Center, Hanes House, Durham, North Carolina, USA⁎Corresponding author. Duke University Medical Center, Box 2914 Med. Center, 347 Hanes House, Durham, North Carolina, 27710 USA. Tel.: +1 919 681 2441; fax: +1 919 684 8675.Search for more papers by this authorK.S.H. Yarnall, K.S.H. Yarnall Duke University Medical Center, Hanes House, Durham, North Carolina, USASearch for more papers by this authorJ. Fortney, J. Fortney Mailman School of Public Health, Columbia University, New York, NY, USASearch for more papers by this author C. Hoyo, Corresponding Author C. Hoyo cathrine.hoyo@duke.edu Duke University Medical Center, Hanes House, Durham, North Carolina, USA⁎Corresponding author. Duke University Medical Center, Box 2914 Med. Center, 347 Hanes House, Durham, North Carolina, 27710 USA. Tel.: +1 919 681 2441; fax: +1 919 684 8675.Search for more papers by this authorK.S.H. Yarnall, K.S.H. Yarnall Duke University Medical Center, Hanes House, Durham, North Carolina, USASearch for more papers by this authorJ. Fortney, J. Fortney Mailman School of Public Health, Columbia University, New York, NY, USASearch for more papers by this author First published: 09 May 2007 https://doi.org/10.1016/j.ijgo.2007.04.010Citations: 2Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat No abstract is available for this article.Citing Literature Volume98, Issue1July 2007Pages 56-57 RelatedInformation}, number={1}, journal={International Journal of Gynecology & Obstetrics}, publisher={Wiley}, author={Hoyo, C. and Yarnall, K.S.H. and Fortney, J.}, year={2007}, month={May}, pages={56–57} } @article{hoyo_berchuck_halabi_bentley_moorman_calingaert_schildkraut_2005, title={Anthropometric Measurements and Epithelial Ovarian Cancer Risk in African–American and White women}, volume={16}, ISSN={0957-5243 1573-7225}, url={http://dx.doi.org/10.1007/s10552-005-3205-y}, DOI={10.1007/s10552-005-3205-y}, abstractNote={Previous studies of anthropometric factors and ovarian cancer risk have been inconsistent and none have evaluated the association among African-American women. Data from a population-based, case-control study of 593 cases and 628 controls were used to evaluate ovarian cancer risk in relation to weight, height, body mass index (BMI) and waist-to-hip ratio (WHR). Odds ratios (ORs) and 95% confidence intervals (CIs) were computed and established risk factors were adjusted for using logistic regression models, stratified by race. Among all races, weight at age 18, WHR, weight and BMI one year prior to interview were associated with elevated ovarian cancer risk. When stratified by race, the association between WHR and ovarian was similar among Whites and among African Americans. However, African-American women in the fourth quartile of height had an elevated risk of ovarian cancer (OR = 3.2; 95% CI = 1.3-7.8), but this risk was not apparent in Whites (OR = 1.0; 95% CI = 0.7-1.4). These findings support the hypothesis that obesity is an important risk factor of ovarian cancer among African-Americans and Whites and also suggest that height may be a risk factor specific to African-Americans.}, number={8}, journal={Cancer Causes & Control}, publisher={Springer Science and Business Media LLC}, author={Hoyo, Cathrine and Berchuck, Andrew and Halabi, Susan and Bentley, Rex C. and Moorman, Patricia and Calingaert, Brian and Schildkraut, Joellen M.}, year={2005}, month={Oct}, pages={955–963} } @article{hoyo_yarnall_skinner_moorman_sellers_reid_2005, title={Pain predicts non-adherence to pap smear screening among middle-aged African American women}, volume={41}, ISSN={0091-7435}, url={http://dx.doi.org/10.1016/j.ypmed.2004.11.021}, DOI={10.1016/j.ypmed.2004.11.021}, abstractNote={Middle-aged African American women have the highest incidence and mortality of invasive cervical cancer in the United States and the lowest adherence to pap smear screening.In 2001, we identified factors associated with non-adherence to screening recommendations using three focus group interviews and subsequently developed a questionnaire administered to 144 African American women aged 45 to 65 years.The perception that the Pap test was painful was associated with non-adherence to screening recommendations (OR = 4.78; 95%CI: 1.67-13.7). Difficulty to pay for the office visit coupled with perceived pain was associated with a nearly sixfold increase in risk of non-adherence (OR = 5.8; 95%CI: 2.8-15.5). Previously identified barriers to screening including lower education and socioeconomic status, poor access to care, knowledge of and exposure to known risk factors of invasive cervical cancer, cancer fatalism, and perceived racism were not independently associated with non-adherence.These data suggest that, among middle-aged African American women, future interventions addressing pain during a Pap test will likely increase acceptability of and adherence to cervical cancer screening. Pain could be addressed either by providing information during the pap test and/or using smaller lubricated speculums.}, number={2}, journal={Preventive Medicine}, publisher={Elsevier BV}, author={Hoyo, Cathrine and Yarnall, Kimberly S.H. and Skinner, Celette Sugg and Moorman, Patricia G. and Sellers, Denethia and Reid, LaVerne}, year={2005}, month={Aug}, pages={439–445} }