Effects of three common polymorphisms in microRNAs on lung cancer risk: a meta-analysis

Background: Many studies demonstrated that miRNAs could affect the initiation and progression of malignant tumor. Recently, many studies on the association of these three common polymorphisms (miR-146a, miR-196a2 and miR-499) with lung cancer risk found inconsistent results. Methods: These studies were collected from PubMed, Wanfang, VIP and CNKI database. ORs (odds ratios) with 95% CIs (confidence intervals) were used to assess the association between three genetic polymorphisms and the risk of lung cancer. All results were performed by using the Stata 14 software. Results: Eleven studies including 9,231 lung cancer cases and 9,280 case-free controls were analyzed in this meta-analysis. The analysis revealed that a significant association was found between miR-146a polymorphism and lung cancer (CG vs. CC, GG vs. CC, GG + CG vs. CC, G vs. C: OR =0.859, 95% CI: 0.781-0.945, P=0.002; OR =0.846, 95% CI: 0.751-0.953, P=0.006; OR =0.855, 95% CI: 0.782-0.935, P=0.001; OR= 0.910, 95% CI: 0.859-0.964, P=0.001, respectively). We also found that the significant association between miR-146a polymorphism and the risk of lung cancer was found among hospital-based population. We found that miR-196a2 polymorphism was associated with an increased lung cancer risk (CC vs. TT: OR =1.200, 95% CI: 1.056-1.364, P=0.005; CC + CT vs. TT: OR =1.117, 95% CI: 1.011-1.235, P=0.029; CC vs. CT + TT: OR =1.123, 95% CI: 1.009-1.251, P=0.034; C vs. T: OR =1.089, 95% CI: 1.022-1.161, P=0.008, respectively). For the Asian samples alone, we achieved the same results. Subgroup analysis found that a statistically association between miR-196a2 (rs11614913) and the lung cancer risk among hospital-based. There was significant association between miR-499 and lung cancer (AG vs. AA: OR =1.131, 95% CI: 1.022-1.252, P=0.018; GG vs. AA: OR =1.702, 95% CI: 1.093-2.650, P=0.019; AG + GG vs. AA: OR =1.207, 95% CI: 1.042-1.398, P=0.012; GG vs. AG + AA: OR =1.640, 95% CI: 1.066-2.523, P=0.024; G vs. A: OR =1.226, 95% CI: 1.026-1.464, P=0.025, respectively). Conclusions: All three common polymorphisms in microRNA are associated with the risk of lung cancer.