MiRNA-processing gene methylation and cancer risk

Brian T. Joyce, Yinan Zheng, Zhou Zhang, Lei Liu, Masha Kocherginsky, Robert Murphy, Chad J. Achenbach, Jonah Musa, Firas Wehbe, Allan Just, Jincheng Shen, Pantel Vokonas, Joel Schwartz, Andrea A. Baccarelli, Lifang Hou

Research output: Contribution to journalArticlepeer-review

16 Scopus citations


Background: Dysregulation of miRNA and methylation levels are epigenetic hallmarks of cancer, potentially linked via miRNAprocessing 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. Methods: 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. Results: Methylation of three CpGs (DROSHA: Cg23230564, TNRC6B: Cg06751583, and TNRC6B: Cg21034183) was prospectively associated with time to cancer development (positively for cg06751583, inversely for cg23230564 and cg21034183), whereas methylation of one CpG site (DROSHA: Cg16131300) was positively associated with cancer prevalence. Conclusions: DNA methylation of DROSHA, a key miRNAprocessing gene, and TNRC6B may play a role in early carcinogenesis. Impact: 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.

Original languageEnglish
Pages (from-to)550-557
Number of pages8
JournalCancer Epidemiology Biomarkers and Prevention
Issue number5
StatePublished - May 2018


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