title: Three common functional polymorphisms in microRNA encoding genes in the susceptibility to hepatocellular carcinoma: a systematic review and meta-analysis.
abstract: Emerging evidences have shown that common genetic polymorphisms in microRNAs may be associated with the development of hepatocellular carcinoma (HCC); but individually published studies and previous meta-analyses revealed inconclusive results. The aims of this review and meta-analysis are to assess whether common single-nucleotide polymorphisms (SNPs) in the genes encoding the microRNAs are associated with susceptibility to HCC development and clinicopathologic characteristics of hepatitis B virus (HBV) related HCC. A computerized search was performed in PubMed, Embase, Web of Science and China BioMedicine (CBM) databases to identify relevant articles published before January 1st 2013. Ten case-control studies were assessed with a total of 3437 cases and 3437 healthy controls. Three common functional SNPs in miRNA-encoding genes were found, including miR-146a G>C (rs2910164), miR-196a-2 C>T (rs11614913) and miR-499 T>C (rs3746444). This meta-analysis revealed that the miR-146a C variant was associated with a decrease in HCC risk, especially among Asian and male populations; while the miR-196a-2 T variant was associated with susceptibility to HCC among Caucasian populations. However, we failed to find any significant correlations between the miR-499 C polymorphism and HCC risks. When further stratification on HBV status was conducted, a similar trend of association between the three SNPs and the HBV-related HCC risks was observed, but these results were not statistically significant due to small sample sizes. The current meta-analysis demonstrates that SNPs contained in the genes encoding miR-146a and miR-196a-2 may play a major role in genetic susceptibility to HCC.
authors.affiliation: Department of Infectious Diseases, Ruijin Hospital, Shanghai, China.
authors.forename: Yumin
authors.initials: Y
authors.lastname: Xu
authors.forename: Liwen
authors.initials: L
authors.lastname: Li
authors.forename: Xiaogang
authors.initials: X
authors.lastname: Xiang
authors.forename: Hui
authors.initials: H
authors.lastname: Wang
authors.forename: Wei
authors.initials: W
authors.lastname: Cai
authors.forename: Jingdong
authors.initials: J
authors.lastname: Xie
authors.forename: Yan
authors.initials: Y
authors.lastname: Han
authors.forename: Shishan
authors.initials: S
authors.lastname: Bao
authors.forename: Qing
authors.initials: Q
authors.lastname: Xie
mesh_terms: D006528:Carcinoma, Hepatocellular / Q000235:genetics*; D016022:Case-Control Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics*; D035683:MicroRNAs / Q000235:genetics*; D011110:Polymorphism, Genetic
chemical_list: D035683:MicroRNAs
keywords: CI; HBV; HCC; HWE; Hardy–Weinberg equilibrium; Hepatocellular carcinoma; Meta-analysis; MicroRNA; OR; PCR-LDR; PCR-RFLP; PCR-ligase detection reaction; PIRA-PCR; Polymorphism; SNP; Systematic review; confidence interval; hepatitis B virus; hepatocellular carcinoma; odds ratio; polymerase chain reaction-restriction fragment length polymorphism; primer introduced restriction analysis-PCR; single nucleotide polymorphisms