Association between PEG3 DNA methylation and high-grade cervical intraepithelial neoplasia

Infectious Agents and Cancer

Cathrine Hoyo¹  Dereje Jima¹  David Skaar¹  Jennifer S. Smith²  Margaret Gradison³  Kimberly S. H. Yarnall³  Francine Overcash³  Claire Bosire⁴  Zhiqing Huang⁵  Anne Ford⁵  Susan K. Murphy⁵  Fidel Valea⁶  Rex Bentley⁷  Adriana C. Vidal⁸ 

[1] Department of Biological Sciences, Center for Human Health and the Environment, North Carolina State University, Raleigh, NC, USA;Department of Epidemiology, Gillings School of Global Public Health and Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC, USA;Department of Family Medicine and Community Health, Duke University School of Medicine, Durham, NC, USA;Department of Health Behavior, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, NC, USA;Department of Obstetrics and Gynecology, Division of Reproductive Sciences, Duke University School of Medicine, Durham, NC, USA;Department of Obstetrics and Gynecology, Virginia Tech Carilion School of Medicine, Roanoke, VA, USA;Department of Pathology, Duke University School of Medicine, Durham, NC, USA;Department of Surgery, Cedars-Sinai Medical Center, Los Angeles, CA, USA;

关键词: Cervical intraepithelial neoplasia;    Gene methylation;    Imprinted gene;    Human papillomavirus;   

DOI  :  10.1186/s13027-021-00382-3

来源: Springer

【 摘 要 】

BackgroundEpigenetic mechanisms are hypothesized to contribute substantially to the progression of cervical intraepithelial neoplasia (CIN) to cervical cancer, although empirical data are limited.MethodsWomen (n = 419) were enrolled at colposcopic evaluation at Duke Medical Center in Durham, North Carolina. Human papillomavirus (HPV) was genotyped by HPV linear array and CIN grade was ascertained by biopsy pathologic review. DNA methylation was measured at differentially methylated regions (DMRs) regulating genomic imprinting of the IGF2/H19, IGF2AS, MESTIT1/MEST, MEG3, PLAGL1/HYMAI, KvDMR and PEG10, PEG3 imprinted domains, using Sequenom-EpiTYPER assays. Logistic regression models were used to evaluate the associations between HPV infection, DMR methylation and CIN risk overall and by race.ResultsOf the 419 participants, 20 had CIN3+, 52 had CIN2, and 347 had ≤ CIN1 (CIN1 and negative histology). The median participant age was 28.6 (IQR:11.6) and 40% were African American. Overall, we found no statistically significant association between altered methylation in selected DMRs and CIN2+ compared to ≤CIN1. Similarly, there was no significant association between DMR methylation and CIN3+ compared to ≤CIN2. Restricting the outcome to CIN2+ cases that were HR-HPV positive and p16 staining positive, we found a significant association with PEG3 DMR methylation (OR: 1.56 95% CI: 1.03–2.36).ConclusionsWhile the small number of high-grade CIN cases limit inferences, our findings suggest an association between altered DNA methylation at regulatory regions of PEG3 and high grade CIN in high-risk HPV positive cases.

【 授权许可】

CC BY