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Association between PEG3 DNA methylation and high-grade cervical intraepithelial neoplasia
Infectious Agents and Cancer ( IF 3.7 ) Pub Date : 2021-06-13 , DOI: 10.1186/s13027-021-00382-3
Claire Bosire 1 , Adriana C Vidal 2 , Jennifer S Smith 3 , Dereje Jima 4 , Zhiqing Huang 5 , David Skaar 4 , Fidel Valea 6 , Rex Bentley 7 , Margaret Gradison 8 , Kimberly S H Yarnall 8 , Anne Ford 5 , Francine Overcash 8 , Susan K Murphy 5 , Cathrine Hoyo 4
Affiliation  

Epigenetic mechanisms are hypothesized to contribute substantially to the progression of cervical intraepithelial neoplasia (CIN) to cervical cancer, although empirical data are limited. 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. 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). 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.

中文翻译:

PEG3 DNA甲基化与宫颈高级别上皮内瘤变的关系

尽管经验数据有限,但假设表观遗传机制对宫颈上皮内瘤变 (CIN) 向宫颈癌的进展有很大贡献。女性(n = 419)参加了北卡罗来纳州达勒姆杜克医疗中心的阴道镜评估。人乳头瘤病毒(HPV)通过HPV线性阵列进行基因分型,CIN分级通过活检病理检查确定。使用 Sequenom-EpiTYPER 测定法在调节 IGF2/H19、IGF2AS、MESTIT1/MEST、MEG3、PLAGL1/HYMAI、KvDMR 和 PEG10、PEG3 印记结构域的基因组印记的差异甲基化区域 (DMR) 处测量 DNA 甲基化。逻辑回归模型用于评估 HPV 感染、DMR 甲基化和整体和种族之间的 CIN 风险之间的关联。在 419 名参与者中,20 人患有 CIN3+,52 人患有 CIN2,和 347 有 ≤ CIN1(CIN1 和阴性组织学)。参与者的中位年龄为 28.6 岁(IQR:11.6),40% 是非裔美国人。总体而言,与≤CIN1 相比,我们发现选定 DMR 和 CIN2+ 中甲基化改变之间没有统计学上的显着关联。同样,与≤CIN2 相比,DMR 甲基化与 CIN3+ 之间没有显着关联。将结果限制为 HR-HPV 阳性和 p16 染色阳性的 CIN2+ 病例,我们发现与 PEG3 DMR 甲基化显着相关(OR:1.56 95% CI:1.03-2.36)。虽然少数高级别 CIN 病例限制了推断,但我们的研究结果表明 PEG3 调节区域的 DNA 甲基化改变与高危 HPV 阳性病例中的高级别 CIN 之间存在关联。6) 和 40% 是非裔美国人。总体而言,与≤CIN1 相比,我们发现选定 DMR 和 CIN2+ 中甲基化改变之间没有统计学上的显着关联。同样,与≤CIN2 相比,DMR 甲基化与 CIN3+ 之间没有显着关联。将结果限制为 HR-HPV 阳性和 p16 染色阳性的 CIN2+ 病例,我们发现与 PEG3 DMR 甲基化显着相关(OR:1.56 95% CI:1.03-2.36)。虽然少数高级别 CIN 病例限制了推断,但我们的研究结果表明 PEG3 调节区域的 DNA 甲基化改变与高危 HPV 阳性病例中的高级别 CIN 之间存在关联。6) 和 40% 是非裔美国人。总体而言,与≤CIN1 相比,我们发现选定 DMR 和 CIN2+ 中甲基化改变之间没有统计学上的显着关联。同样,与≤CIN2 相比,DMR 甲基化与 CIN3+ 之间没有显着关联。将结果限制为 HR-HPV 阳性和 p16 染色阳性的 CIN2+ 病例,我们发现与 PEG3 DMR 甲基化显着相关(OR:1.56 95% CI:1.03-2.36)。虽然少数高级别 CIN 病例限制了推断,但我们的研究结果表明 PEG3 调节区域的 DNA 甲基化改变与高危 HPV 阳性病例中的高级别 CIN 之间存在关联。与≤CIN2相比,DMR甲基化与CIN3+之间没有显着关联。将结果限制为 HR-HPV 阳性和 p16 染色阳性的 CIN2+ 病例,我们发现与 PEG3 DMR 甲基化显着相关(OR:1.56 95% CI:1.03-2.36)。虽然少数高级别 CIN 病例限制了推断,但我们的研究结果表明 PEG3 调节区域的 DNA 甲基化改变与高危 HPV 阳性病例中的高级别 CIN 之间存在关联。与≤CIN2相比,DMR甲基化与CIN3+之间没有显着关联。将结果限制为 HR-HPV 阳性和 p16 染色阳性的 CIN2+ 病例,我们发现与 PEG3 DMR 甲基化显着相关(OR:1.56 95% CI:1.03-2.36)。虽然少数高级别 CIN 病例限制了推断,但我们的研究结果表明 PEG3 调节区域的 DNA 甲基化改变与高危 HPV 阳性病例中的高级别 CIN 之间存在关联。
更新日期:2021-06-14
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