Highlighted, when stratified analysis was conducted by cancer type, rs2910164 polymorphism was also significantly associated with an increased risk of bladder cancer in allelic, homozygote and recessive models.
We found that CT (miR-196a2, C>T rs11614913) was a risk factor for renal cell carcinoma (CT vs. CC: OR = 1.72, 95%CI = 1.05-2.80, <i>P</i> = 0.03, <i>I</i><sup>2</sup> = 66%), especially in Asian population (CT vs. CC: OR = 1.17, 95%CI = 1.04-1.32, <i>P</i> < 0.01, <i>I</i><sup>2</sup> = 0%). miR-146a G>C rs2910164 was a protective factor of urological cancers (C vs. G: OR = 0.87, 95%CI = 0.81-0.93, <i>P</i> < 0.01, <i>I</i><sup>2</sup> = 0%), especially for bladder cancer. miR-499 A>G rs3746444 was correlated with an increased risk of urological cancers, specifically in Asian population.
Our results suggested hsa-mir-196a2 rs11614913 C/T is associated with a significantly decreased risk of bladder cancer and hsa-mir-146a rs2910164 GG genotype is associated with clinical stage and metastasis in bladder cancer.
However, in stratified analysis, we found that either the rs2910164 C allele or the CC genotype was protective against bladder cancer, prostate cancer, cervical cancer, and colorectal cancer, whereas it was a risk factor for papillary thyroid carcinoma and squamous cell carcinoma of the head and neck (SCCHN).
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.