Functional miR-146a, miR-149, miR-196a2 and miR-499 polymorphisms and the susceptibility to hepatocellular carcinoma: An updated meta-analysis.

Objective: Single nucleotide polymorphisms of miRNAs play important roles in the pathogenesis of hepatocellular carcinoma (HCC). To evaluate the association between four common miRNAs (miR-146a rs2910164; miR-149 rs2292832; miR-196a2 rs11614913 and miR-499 rs3746444) and HCC risk, an updated meta-analysis was performed.

Methods: 32 studies including 12,405 HCC cases and 15,056 controls were used for this meta-analysis. There were 22 studies with 7894 cases and 10,221 controls for miR-146a, 9 studies with 2684 HCC cases and 3464 controls for miR-149, 17 studies with 6937 cases and 8217 controls for miR-196a2 and 16 studies with 4158 cases and 5264 controls for miR-499. Odds radios (ORs) and 95% confidence intervals (CIs) were used to assess the HCC risk.

Results: Meta-analysis showed that miR-146a was associated with HCC risk under the heterozygote model (OR=1.10, 95%CI=1.03-1.17, P=0.007), whereas no association was found in Caucasian using all genetic models. For miR-196a2 polymorphism, an increased risk of HCC was observed based on four models (C vs T: OR=1.15, 95%CI=1.05-1.26, P=0.003; CC vs TT: OR=1.35, 95%CI=1.12-1.63, P=0.002; CC+CT vs TT: OR=1.20, 95%CI=1.04-1.37, P=0.01 and CC vs CT+TT: OR=1.23, 95%CI=1.06-1.42, P=0.006). Association of miR-499 with HCC risk was only detected in the subgroup of studies which did not use polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP) under the allelic, heterozygote and dominant models. However, negative results were obtained for the association of miR-149 and HCC susceptibility.

Conclusion: Our results suggest that miR-146a and miR-196a2 polymorphisms are associated with increased risk of HCC, especially in Asian.