TY - JOUR
T1 - MiRNA-processing gene methylation and cancer risk
AU - Joyce, Brian T.
AU - Zheng, Yinan
AU - Zhang, Zhou
AU - Liu, Lei
AU - Kocherginsky, Masha
AU - Murphy, Robert
AU - Achenbach, Chad J.
AU - Musa, Jonah
AU - Wehbe, Firas
AU - Just, Allan
AU - Shen, Jincheng
AU - Vokonas, Pantel
AU - Schwartz, Joel
AU - Baccarelli, Andrea A.
AU - Hou, Lifang
N1 - Publisher Copyright:
© 2018 American Association for Cancer Research.
PY - 2018/5
Y1 - 2018/5
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85047738682&partnerID=8YFLogxK
U2 - 10.1158/1055-9965.EPI-17-0849
DO - 10.1158/1055-9965.EPI-17-0849
M3 - Article
C2 - 29475968
AN - SCOPUS:85047738682
SN - 1055-9965
VL - 27
SP - 550
EP - 557
JO - Cancer Epidemiology Biomarkers and Prevention
JF - Cancer Epidemiology Biomarkers and Prevention
IS - 5
ER -