Abstract

BackgroundEmerging evidence has shown that microRNAs (miRNAs) participate in human carcinogenesis as tumor suppressors or oncogenes. Single nucleotide polymorphism (SNP) located in the miRNAs may influence the function of mature miRNAs and then affect the processing of carcinogenesis. It has been suggested that two common SNPs rs2910164 in miR-146a and rs3746444 in miR-499 are associated with susceptibility to hepatocellular carcinoma (HCC). However, published results are inconsistent and inconclusive. To acquire a more precise effect of the association between these polymorphisms and HCC risk, we performed this meta-analysis.Methodology/Principal FindingsWe have conducted a search of case-control studies on the associations of SNPs rs2910164 and/or rs3746444 with susceptibility to HCC in PubMed, ScienceDirect, Cochrane Central Register of Controlled Trials, and Chinese National Knowledge Infrastructure databases for the period up to Sep 10th, 2012. A total of 6 studies were identified with 2071 cases and 2350 controls for miR-146a rs2910164 polymorphism, 667 cases and 1006 controls for miR-499 rs3746444 polymorphism. It was found that neither allele frequency nor genotype distribution of the two polymorphisms was associated with risk of HCC in all genetic models. Similarly, subgroup analysis in Asian population showed no associations between the two SNPs and the susceptibility to HCC.Conclusions/SignificanceThis meta-analysis suggests that miR-146a rs2910164 and miR-499 rs3746444 polymorphisms may not be associated with the risk of HCC, especially for Asian population. However, well-designed studies with larger sample size and more detailed data are needed to confirm these conclusions.

Highlights

  • Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide [1]

  • All the studies included in our metaanalysis employed the same genotyping methods: polymerase chain reaction-restriction fragment length polymorphism (PCRRFLP), except the study of Zhang XW [14]. (PIRA—PCR)

  • The research on microRNAs has provided us a new approach to understand the molecular mechanism of hepatocellular carcinoma (HCC) and a new therapy to treat HCC [18]

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Summary

Introduction

Epidemiological evidence suggests that the major risk factor for HCC is chronic hepatitis B virus (HBV) and/or hepatitis C virus (HCV) infection [2]. HBV and HCV infections are the major causes of HCC, only a fraction of infected patients develop HCC during their lifetime, which suggests that the etiology of HCC is still not yet clarified [4]. MicroRNAs (miRNAs) are small non-coding, single-stranded RNA molecules with typical length of 22 nucleotides. Single nucleotide polymorphism (SNP) located in the miRNAs may influence the function of mature miRNAs and affect the processing of carcinogenesis. It has been suggested that two common SNPs rs2910164 in miR-146a and rs3746444 in miR-499 are associated with susceptibility to hepatocellular carcinoma (HCC). To acquire a more precise effect of the association between these polymorphisms and HCC risk, we performed this meta-analysis

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