DNA repair gene XRCC1 Arg194Trp polymorphism and susceptibility to hepatocellular carcinoma: A meta-analysis.

Wenyan Li,Yongxian Gui,Junjie Bian,Feng Yang

doi:10.3892/ol.2014.2351

Abstract

The arginine194tryptophan (Arg194Trp) polymorphism in the X-ray repair cross-complementing group 1 (XRCC1) gene has been reported to be associated with hepatocellular carcinoma (HCC), however, the results from previous studies are conflicting. The present study aimed to investigate the association between the XRCC1 Arg194Trp polymorphism and the risk of HCC, using a meta-analysis of previously published studies. PubMed (http://www.ncbi.nlm.nih.gov/pubmed/), Google Scholar (http://scholar.google.co.uk/) and the China National Knowledge Infrastructure databases (http://www.cnki.net/) were systematically searched to identify relevant studies published prior to October 2013. A meta-analysis was performed to examine the association between the Arg194Trp gene polymorphism and the susceptibility to HCC. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated. The meta-analysis consisted of six case-control studies that included 1,451 HCC cases and 1,398 healthy controls. Meta-analysis results based on all the studies showed no significant association between the XRCC1 Arg194Trp gene polymorphism and the risk of HCC (Trp/Trp vs. Arg/Arg: OR, 1.17; 95% CI, 0.89–1.55; Trp/Trp vs. Arg/Trp: OR, 0.94; 95% CI, 0.59–1.51; dominant model: OR, 0.97; 95% CI, 0.63–1.49; recessive model: OR, 1.22; 95% CI, 0.89–1.67). In the subgroup analysis, three studies with sample sizes of >300 produced similar results that indicated that the Arg194Trp gene polymorphism had no association with an increased or decreased risk of HCC. The pooled ORs were not markedly different following the exclusion of two studies deviating from the Hardy-Weinberg equilibrium in the control group, which indicated the reliability of the meta-analysis results. In conclusion, the XRCC1 Arg194Trp polymorphism may not be a risk or protective factor for HCC. Further large and well-designed studies are required to confirm these results.

Highlights

Hepatocellular carcinoma (HCC) is a common primary liver cancer with a rising incidence globally [1]
In the overall and subgroup meta‐analyses, the strength of the association between the X‐ray repair cross‐complementing group 1 (XRCC1) Arg194Trp gene polymorphism and the HCC risk was measured by odds ratios (ORs) and 95% confidence intervals (CIs)
In the stratified analysis by sample size, no significant association was identified between the Arg194Trp gene polymorphism and HCC (Trp/Trp vs. Arg/Arg: Odds ratios (ORs), 1.17; 95% confidence intervals (95% CIs), 0.85‐1.60; Trp/Trp vs. Arg/Trp: OR, 1.07; 95% CI, 0.78‐1.49; dominant model: OR, 0.88; 95% CI, 0.65‐1.19; recessive model: OR, 1.11; 95% CI, 0.86‐1.44)

Summary

Introduction

Hepatocellular carcinoma (HCC) is a common primary liver cancer with a rising incidence globally [1]. >300 validated single nucleotide polymorphisms (SNPs) have been identified and described in the XRCC1 gene, only three common SNPs have been extensively studied: Argenine399glutamine (Arg399Gln; rs25487, G/A substitution at position 28,152 on exon 10), argenine280histidine (Arg280His; rs25489, G/A substitution at position 27,466 on exon 9) and arginine194tryptophan (Arg194Trp; rs1799782, C/T substitution at position 26,304 on exon 6). These variations were shown to be able to alter the function of XRCC1, diminish repair kinetics and lead to altered protein efficiency, eventually inducing the development of cancer [9]

Methods

Results

Conclusion