Association between single-nucleotide polymorphisms in miRNA and breast cancer risk: an updated review

Abstract

Breast cancer (BC), a heterogeneous, aggressive illness with high mortality, is essentially a genomic disease. While the high-penetrance genes BRCA1 and BRCA2 play important roles in tumorigenesis, moderate- and low-penetrance genes are also involved. Single-nucleotide polymorphisms (SNPs) in microRNA (miRNA) genes have recently been identifed as BC risk factors. miRNA genes are currently classifed as low-penetrance. SNPs are the most common vari‑ ations in the human genome. While the role of miRNA SNPs in BC susceptibility has been studied extensively, results have been inconsistent. This review analyzes the results of association studies between miRNA SNPs and BC risk from countries around the world. We conclude that: (a) By continent, the largest proportion of studies to date were conducted in Asia (65.0%) and the smallest proportion in Africa (1.8%); (b) Association studies have been completed for 67 diferent SNPs; (c) 146a, 196a2, 499, 27a, and 423 are the most-studied miRNAs; (d) The SNPs rs2910164 (miRNA146a), rs11614913 (miRNA-196a2), rs3746444 (miRNA-499) and rs6505162 (miRNA-423) were the most widely associ‑ ated with increased BC risk; (e) The majority of studies had small samples, which may afect the precision and power of the results; and (f ) The efect of an SNP on BC risk depends on the ethnicity of the population. This review also discusses potential explanations for controversial fndings.