期刊
HUMAN MUTATION
卷 30, 期 1, 页码 79-84出版社
WILEY
DOI: 10.1002/humu.20837
关键词
microRNA; polymorphism; breast cancer; genetic susceptibility
资金
- Innovative Key Grant of Department of Education [705023]
- Program for Changjiang Scholars and Innovative Research Team in University [IRT0631]
- National Key Basic Research Program [2002CB512908]
Small, noncoding RNA molecules, called microRNAs (miRNAs), are thought to function as either tumor suppressors or oncogenes. Common single, nucleotide polymorphisms (SNPs) in miRNAs may change their property through altering miRNA expression and/or maturation, and thus they may have an effect on thousands of target mRNAs, resulting in diverse functional consequences. However, it remains largely unknown whether miRNA SNPs may alter cancer susceptibility. We evaluated the associations of selected four SNPs (rs2910164, rs2292832, rs11614913, and rs3746444) in pre-miRNAs (hsa-mir-146a, hsa-mir-149, hsa-mir-196a2, and hsa-mir-499) with breast cancer risk in a case-control study of 1,009 breast cancer cases and 1,093 cancer-free controls in a population of Chinese women and we found that hsa-mir.196a2 rs11614913:T > C and hsa-mir-499 rs3746444:A > G variant genotypes were associated with significantly increased risks of breast cancer (odds ratio [OR], 1.23; 95% confidence interval [CI], 1.02-1.48 for rs11614913:T > C; and OR, 1,25; 95% CI, 1.02-1.51 for rs3746444:A > G in a dominant genetic model) in a dose,effect manner (P for trend was 0.010 and 0.037, respectively). These findings suggest, for the first time, that common SNPs in miRNAs may contribute to breast cancer susceptibility. Further functional characterization of miRNA SNPs and their influences on target mRNAs may provide underlying mechanisms for the observed associations and disease etiology.
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