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

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dc.contributor.authorBosire, Claireen
dc.contributor.authorVidal, Adriana C.en
dc.contributor.authorSmith, Jennifer S.en
dc.contributor.authorJima, Derejeen
dc.contributor.authorHuang, Zhiqingen
dc.contributor.authorSkaar, Daviden
dc.contributor.authorValea, Fidelen
dc.contributor.authorBentley, Rexen
dc.contributor.authorGradison, Margareten
dc.contributor.authorYarnall, Kimberly S. H.en
dc.contributor.authorFord, Anneen
dc.contributor.authorOvercash, Francineen
dc.contributor.authorMurphy, Susan K.en
dc.contributor.authorHoyo, Cathrineen
dc.contributor.departmentVirginia Tech Carilion School of Medicineen
dc.date.accessioned2021-06-21T11:42:48Zen
dc.date.available2021-06-21T11:42:48Zen
dc.date.issued2021-06-13en
dc.date.updated2021-06-20T03:42:52Zen
dc.description.abstractBackground Epigenetic mechanisms are hypothesized to contribute substantially to the progression of cervical intraepithelial neoplasia (CIN) to cervical cancer, although empirical data are limited. Methods Women (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. Results Of 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). Conclusions While 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.en
dc.description.versionPublished versionen
dc.format.mimetypeapplication/pdfen
dc.identifier.citationInfectious Agents and Cancer. 2021 Jun 13;16(1):42en
dc.identifier.doihttps://doi.org/10.1186/s13027-021-00382-3en
dc.identifier.urihttp://hdl.handle.net/10919/103910en
dc.language.isoenen
dc.rightsCreative Commons Attribution 4.0 Internationalen
dc.rights.holderThe Author(s)en
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.titleAssociation between PEG3 DNA methylation and high-grade cervical intraepithelial neoplasiaen
dc.title.serialInfectious Agents and Canceren
dc.typeArticle - Refereeden
dc.type.dcmitypeTexten
dc.type.dcmitypeStillImageen

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