MicroRNAs (miRNAs) play important roles in numerous cellular processes, including development, proliferation, apoptosis, and carcinogenesis. We hypothesized that genetic variations in miRNAs are associated with bladder cancer risk and prognosis. We performed a systematic survey of single nucleotide polymorphisms (SNPs) in miRNAs and evaluated association of selected SNPs with bladder cancer risk and recurrence. The functionality of these miRNA SNPs was further examined by a series of molecular biological assays. Through bioinformatics analysis, five miRNA SNPs were selected for the association study. We found that miR-146a rs2910164 C allele was associated with a significant decreased risk of bladder cancer in both test and validation sets as well as in the combined set (
P = 2.92×10
-4). Furthermore, rs2910164 GC/CC genotypes conferred a significantly reduced recurrence compared with the GG genotype (
P = 0.016). Functional analysis revealed that miR-146a rs2910164 C allele inhibited cell proliferation and significantly downregulated
IRAK1 and
TRAF6 expressions in bladder cancer cells. Additional examination of 64 bladder tissues revealed that individuals carrying the C allele had increased expression levels of miR-146a compared with those carrying the G allele (
P = 0.010). Our findings demonstrate that miR-146a rs2910164 plays important roles in the risk and recurrence of bladder cancer.
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