Ethnicity modifies the association between functional microRNA polymorphisms and breast cancer risk: a HuGE meta-analysis

Common functional polymorphisms in the promoter region of microRNAs (miRNAs), based on multiple lines of evidence, might participate in transcriptional regulation and other biological processes, which interact to increase the risk of developing breast cancer. Since 2005, many studies have investigated the association between breast cancer risk and common single nucleotide polymorphisms (SNPs) in miRNAs. However, the findings of several meta-analyses are inconclusive or ambiguous. The aim of this Human Genome Epidemiology meta-analysis was to determine more precisely the relationship between common miRNA polymorphisms and breast cancer risk. Twelve case-control studies with a total of 7,170 breast cancer patients and 8,783 healthy controls were included. Eight SNPs in miRNA genes were examined. When all eligible studies were pooled in the meta-analysis, the miR-196a-2 rs11614913*T, miR-499 rs3746444*T, and miR-605 rs2043556*A alleles predicted a decreased risk of breast cancer among Asians, while not Caucasians. In addition, the miR-27a rs895919*C allele might be a protective factor for breast cancer among Caucasians. However, for the miR-146a rs2910164 (G > C), miR-149 rs2292832 (G > T), miR-373 rs12983273 (C > T), and miR-423 rs6505162 (C > A) polymorphisms, we failed to find any significant association with the risk of breast cancer in any genetic model. In conclusion, the current meta-analysis supports that the miR-196a-2 rs11614913*T, miR-499 rs3746444*T, miR-605 rs2043556*A, and miR-27a rs895919*C alleles might be protective factors for breast cancer.