Functional miR-146a, miR-149, miR-196a2 and miR-499 polymorphisms and the susceptibility to hepatocellular carcinoma: An updated meta-analysis.
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.
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.
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.
Our results suggest that miR-146a and miR-196a2 polymorphisms are associated with increased risk of HCC, especially in Asian.
Zheng L
，Zhuang C
，Zhao J
，Ming L
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Study of the association between five polymorphisms and risk of hepatocellular carcinoma: A meta-analysis.
Recently, several studies have investigated the association between polymorphisms in miR-146a rs2910164, miR-196a2 rs11614913, miR-499 rs3746444, miR-149 rs229283, miR-34b/c rs4938723, and hepatocellular carcinoma (HCC), which showed inconclusive results.
A publication search was performed in PubMed, ExcerptaMedica Database, Chinese Biomedical Literature Database, and Chinese National Knowledge Infrastructure to collect relevant medical data published through February 2016. The aim of this study was to ascertain the association between HCC and micro-RNAs. A total of 21 studies were included in our study, which showed that miR-146a rs2910164 polymorphism has a significant association with HCC in the allele, recessive, and homozygous models overall [allele model: odds ratio (OR) = 0.927, 95% confidence interval (CI): 0.869-0.988, p = 0.02; recessive model: OR = 0.893, 95% CI: 0.814-0.981, p = 0.018; homozygous model: OR = 0.853, 95% CI: 0.744-0.978, p = 0.023] and in Asian populations (allele model: OR = 0.921, 95% CI: 0.863-0.983, p = 0.014; recessive model: OR = 0.893, 95% CI: 0.814-0.981, p = 0.019; homozygous model: OR = 0.851, 95% CI: 0.741-0.977, p = 0.022). For miR-196a2 rs11614913, significant statistical heterogeneity overall and in Asian populations was identified in the comparison of the allele, recessive, homozygous, and heterozygous models (overall: allele model: OR = 0.889, 95% CI: 0.842-0.94, p < 0.001; recessive model: OR = 0.837, 95% CI: 0.723-0.970, p = 0.018; homozygous model: OR = 0.722, 95%CI: 0.575-0.906, p = 0.005; heterozygous model: OR = 0.532, 95% CI: 0.37-0.765, p = 0.001), and also has a decreased risk of HCC in Caucasians in all genetic models except for the heterozygous model (allele model: OR = 0.658, 95% CI: 0.49-0.885, p = 0.006; dominant model: OR = 0.641, 95% CI: 0.418-0.981, p = 0.041; recessive model: OR = 0.489, 95% CI: 0.278-0.862, p = 0.013; homozygous model: OR = 0.414, 95% CI: 0.222-0.772, p = 0.005). Only the recessive models produced a significant association between miR-499 rs3746444 polymorphism and HCC risk (recessive model: OR = 1.283, 95% CI: 1.008-1.632, p = 0.043).
The analysis for miR-146a rs2910164 polymorphisms by racial decent found the same association between miR-146a rs2910164 polymorphism and susceptibility to HCC in Asians, but no significance risk association was observed in Caucasians. The meta-analysis results showed that miR-196a2 rs11614913 was associated with a decreased risk of HCC in Caucasians in all genetic models except for the heterozygous model. In the Asian population, miR-499 rs3746444 polymorphism was associated with a decreased risk of HCC in recessive models. This meta-analysis showed that no significant statistical heterogeneity was identified in miR-149 rs2292832 and miR-34b/c rs4938723.
Our findings supported the proposition that the polymorphisms of miR-146a rs2910164, miR-196a2 rs11614913, and miR-196a2 rs11614913 may contribute to the susceptibility of HCC.
Yu JY
，Hu F
，Du W
，Ma XL
，Yuan K
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ResearchGate
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