microRNA (miRNA) are small noncoding molecules that function as regulators of the genome. Genetic variants in miRNA binding sites and miRNA genes have begun to be evaluated in relation to disease risk; however, no studies have yet comprehensively evaluated miRNA variants in relation to breast cancer risk. Using a two stage study design, and genome-wide association study (GWAS) data, we evaluated genetic variants within 1,425 miRNA genes (±5kb). In Stage 1, a total of 2,213 common genetic variants were evaluated among 2,876 breast cancer cases and 2,285 controls using data from the Shanghai Breast Cancer Genetics Study. Nominally significant associations (P value ≤0.05) were found for 108 variants in 96 genetic loci (r²≥0.6). In Stage 2, 94 variants in 84 loci were evaluated among 2,225 cases and 2,052 controls from the Seoul Breast Cancer Study; nine variants in eight loci had nominally significant associations. In analyses of the two study stages combined, 14 loci had highly significant associations (P value ≤0.01) and 19 additional loci had significant associations (P value ≤0.05) with breast cancer risk, all with consistent directions of association between the two study stages. These 36 variants in 33 loci have been mapped to 16 miRNA genes, many in the promoter regions. Based on our findings, genetic variants in miRNA genes are likely to contribute to breast cancer susceptibility.

Citation Format: Alicia C. Beeghly-Fadiel, Hyuna Sung, Ben Zhang, Ji-Yeob Choi, Ryan J. Delahanty, Jirong Long, Yu-Tang Gao, Wei Lu, Qiuyin Cai, Xiao Ou Shu, Daehee King, Wei Zheng. Genetic variants in microRNA genes and breast cancer risk. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2557. doi:10.1158/1538-7445.AM2013-2557