Center for Population Epigenetics, Robert H. Lurie Comprehensive Cancer Center and Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois.
Institute for Public Health and Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois.
Cancer Epidemiol Biomarkers Prev. 2018 May;27(5):550-557. doi: 10.1158/1055-9965.EPI-17-0849. Epub 2018 Feb 23.
Dysregulation of miRNA and methylation levels are epigenetic hallmarks of cancer, potentially linked via miRNA-processing genes. Studies have found genetic alterations to miRNA-processing genes in cancer cells and human population studies. Our objective was to prospectively examine changes in DNA methylation of miRNA-processing genes and their associations with cancer risk. We examined cohort data from the Department of Veterans' Affairs Normative Aging Study. Participants were assessed every 3 to 5 years starting in 1999 through 2013 including questionnaires, medical record review, and blood collection. Blood from 686 consenting participants was analyzed using the Illumina 450K BeadChip array to measure methylation at CpG sites throughout the genome. We selected 19 genes based on a literature review, with 519 corresponding CpG sites. We then used Cox proportional hazards models to examine associations with cancer incidence, and generalized estimating equations to examine associations with cancer prevalence. Associations at false discovery rate < 0.05 were considered statistically significant. Methylation of three CpGs (: cg23230564, : cg06751583, and : cg21034183) was prospectively associated with time to cancer development (positively for cg06751583, inversely for cg23230564 and cg21034183), whereas methylation of one CpG site (: cg16131300) was positively associated with cancer prevalence. DNA methylation of , a key miRNA-processing gene, and may play a role in early carcinogenesis. Changes in miRNA processing may exert multiple effects on cancer development, including protecting against it via altered global miRNAs, and may be a useful early detection biomarker of cancer. .
miRNA 和甲基化水平的失调是癌症的表观遗传标志，可能通过 miRNA 处理基因相关联。研究已经在癌细胞和人类群体研究中发现了 miRNA 处理基因的遗传改变。我们的目的是前瞻性地研究 miRNA 处理基因的 DNA 甲基化变化及其与癌症风险的关联。我们检查了退伍军人事务部规范老化研究的队列数据。参与者从 1999 年开始每 3 到 5 年评估一次，包括问卷调查、病历审查和血液采集。从 686 名同意的参与者的血液中使用 Illumina 450K BeadChip 阵列进行分析，以测量整个基因组中 CpG 位点的甲基化。我们根据文献综述选择了 19 个基因，其中有 519 个对应的 CpG 位点。然后，我们使用 Cox 比例风险模型来研究与癌症发病率的关联，使用广义估计方程来研究与癌症患病率的关联。假发现率 < 0.05 的关联被认为具有统计学意义。三个 CpG 位点（: cg23230564、: cg06751583 和 : cg21034183）的甲基化与癌症发展的时间呈前瞻性相关（cg06751583 呈正相关，cg23230564 和 cg21034183 呈负相关），而一个 CpG 位点（: cg16131300）的甲基化与癌症患病率呈正相关。关键 miRNA 处理基因和的 DNA 甲基化可能在早期癌变中发挥作用。miRNA 处理的变化可能对癌症发展产生多种影响，包括通过改变全局 miRNAs 来保护其免受影响，并且可能是癌症的有用早期检测生物标志物。
