Hsa-miR-499 polymorphism (rs3746444) and cancer risk: a meta-analysis of 17 case-control studies

MicroRNAs (miRNAs) are a family of endogenous, small and noncoding RNAs that negatively regulate gene expression by suppressing translation or degrading mRNAs. Recently, many studies investigated the association between hsa-miR-499 rs3746444 polymorphism and cancer risk, which showed inconclusive results.

We conducted a meta-analysis of 17 studies that included 7842 cancer cases and 8989 case-free controls and assessed the strength of the association, using odds ratios (ORs) with 95% confidence intervals (CIs). Overall, hsa-miR-499 rs3746444 polymorphism was associated with higher cancer risk in heterozygote model (AG vs AA, OR=1.15, 95%CI=1.01-1.30, P(heterogeneity)<0.001), dominant genetic model (GG/AG vs AA, OR=1.18, 95% CI=1.04-1.33, P(heterogeneity)<0.001) and allele contrast (G vs A, OR=1.09, 95% CI=1.01-1.18, P(heterogeneity)=0.021). In the stratified analyses, we observed that the GG/AG genotype might modulate breast cancer risk (OR=1.13, 95% CI=1.01-1.26, P(heterogeneity)=0.111) comparing with the AA genotype. Moreover, a significantly increased risk was found among Asian populations in heterozygote model (AG vs AA, OR=1.23, 95% CI=1.06-1.43, P(heterogeneity)<0.001), homozygote model (GG vs AA, OR=1.22, 95% CI=1.02-1.46, P(heterogeneity)=0.319), dominant model (GG/AG vs AA, OR=1.25, 95% CI=1.06-1.39, P(heterogeneity)<0.001) and allele contrast (G vs A, OR=1.14, 95% CI=1.04-1.25, P(heterogeneity)=0.021).

These findings supported that hsa-miR-499 rs3746444 polymorphism contributes to the susceptibility of cancers.