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

IntroductionMicroRNAs (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.Methodology/main resultsWe 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, Pheterogeneity < 0.001), dominant genetic model (GG/AG vs AA, OR = 1.18, 95% CI = 1.04-1.33, Pheterogeneity < 0.001) and allele contrast (G vs A, OR = 1.09, 95% CI = 1.01-1.18, Pheterogeneity = 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, Pheterogeneity = 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, Pheterogeneity < 0.001), homozygote model (GG vs AA, OR = 1.22, 95% CI = 1.02-1.46, Pheterogeneity = 0.319), dominant model (GG/AG vs AA, OR = 1.25, 95% CI = 1.06-1.39, Pheterogeneity < 0.001) and allele contrast (G vs A, OR = 1.14, 95% CI = 1.04-1.25, Pheterogeneity = 0.021).ConclusionsThese findings supported that hsa-miR-499 rs3746444 polymorphism contributes to the susceptibility of cancers.

► The meta-analysis confirm the association between hsa-miR-499 with cancer risk. ► This meta-analysis contain 17 studies. ► We identify the link in subgroup by cancer type, ethnicity and source of control.