2018 journal article
DNA methylation of imprinted gene control regions in the regression of low-grade cervical lesions
INTERNATIONAL JOURNAL OF CANCER, 143(3), 552–560.
author keywords: methylation; imprinted genes; cervical cancer; neoplasia; epigenetics; HPV
MeSH headings : Adult; Aged; Biopsy; CpG Islands; DNA Methylation; Disease Progression; Epigenesis, Genetic; Female; Genomic Imprinting; Humans; Middle Aged; Neoplasm Grading; Neoplasm Staging; Regulatory Sequences, Nucleic Acid; Uterine Cervical Neoplasms / epidemiology; Uterine Cervical Neoplasms / etiology; Uterine Cervical Neoplasms / genetics; Uterine Cervical Neoplasms / pathology; Young Adult
TL;DR:
Altered methylation of imprinted IGF2AS and PEG10 DMRs may play a role in the natural history of CIN1, and further research on imprinted gene DMR methylation is warranted to determine its efficacy as a biomarker for cervical cancer screening.
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UN Sustainable Development Goal Categories
3. Good Health and Well-being
(Web of Science; OpenAlex)
Source: Web Of Science
Added: August 6, 2018
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.