miRNAs play important roles in numerous cellular processes, including development, proliferation, apoptosis, and
carcinogenesis. Because altered expression and function of
miRNAs has been observed in
bladder cancer, we investigated whether genetic variations in
miRNAs are associated with
bladder cancer risk and prognosis. Using bioinformatics tools, we selected five single-nucleotide polymorphisms located in
miRNAs and used these to evaluate
miRNA-disease associations in a two-stage model, consisting of 1,019
bladder cancer cases and 1,182 controls (683 cases and 728 controls in the training set and 336 cases and 454 controls in the test set). We found that miR-146a rs2910164 C allele was associated with significantly decreased risk of
bladder cancer in both the training and test sets, as well as the combined set [OR = 0.80, 95% confidence interval (CI) = 0.71-0.90, P = 2.92 × 10(-4)]. Furthermore, the rs2910164 GC/CC genotypes conferred a significantly reduced risk of recurrence, compared with the GG genotype (P = 0.016). Functional analysis revealed that miR-146a rs2910164 C allele inhibited cell proliferation and significantly downregulated expression of IRAK1 and
TRAF6 in
bladder cancer cells. Additional examination of 64
bladder cancer tissues showed that individuals carrying the C allele had increased expression levels of miR-146a compared with those carrying the G allele (P = 0.010). Taken together, our findings show that miR-146a rs2910164 plays an important role in the risk and recurrence of
bladder cancer, suggesting it may represent a
biomarker for risk prevention and therapeutic intervention. Further larger and prospective cohorts are needed to validate our findings.