Abstract
The potential correlation of X-ray repair cross-complementing group 1 (XRCC1) Arg399Gln polymorphism with hepatocellular carcinoma (HCC) susceptibility is ambiguous. Taking account of inconsistent results of previous meta-analyses and new emerging literatures, we conducted a meta-analysis covering 15 case-control datasets to evaluate the relationship. Relevant studies from Medline, Embase and CNKI were retrieved. A fixed- effect model or a random-effect model, depending on between-study heterogeneity, were applied to estimate the association between XRCC1 polymorphism Arg399Gln and HCC risk with the results presented as odds ratios (ORs) and 95% confidence intervals (95% CIs). In accordance with Hardy-Weinberg equilibrium, 15 studies with data for 6,556 individuals were enrolled in this systematic review. For overall HCC,thr XRCC1 polymorphism Arg399Gln was significantly associated with HCC susceptibility in a homozygote model as well as in a dominant model (G/G vs. A/A, OR=1.253, p=0.028; G/G+A/G vs. A/A, OR= 1.281, p=0.047, respectively), but not in a heterozygote model (A/G vs. A/A, OR=1.271, p=0.066) or a recessive model (G/G vs. A/G + A/A, OR= 1.049, p=0.542). Similar results were also observed on stratification analysis by ethnicity (A/G vs. A/A, OR=1.357, p=0.025; G/G vs. A/A, OR=1.310, p=0.011; G/G+A/G vs. A/A, OR= 1.371, p=0.013). However, no potential contribution of XRCC1 Arg399Gln polymorphism to HCC susceptibility in HBV/HCV subgroups was identified. No publication bias was found in this study. In conclusion, the XRCC1 Arg399Gln polymorphism contributes to HCC susceptibility. Due to the lack of studies in Western countries, further large-sample and rigorous studies are needed to validate the findings.
Highlights
Hepatocellular carcinoma (HCC) is a prevalent malignancy worldwide with a total of 28720 estimated new cases and ranks the fifth common cause resulting in male cancer death in USA (Siegel et al, 2012)
A fixedeffect model or a random-effect model, depending on between-study heterogeneity, were applied to estimate the association between X-ray repair cross-complementing group 1 (XRCC1) polymorphism Arg399Gln and hepatocellular carcinoma (HCC) risk with the results presented as odds ratios (ORs) and 95% confidence intervals
Characteristics of studies After initial screening, 32 of 66 published articles regarding the correlation of XRCC1 polymorphism Arg399Gl and HCC susceptibility were identified, four of which were the postgraduate dissertations (Long et al, 2004; Wang et al, 2006; Su et al, 2008; Wu et al, 2009)
Summary
Hepatocellular carcinoma (HCC) is a prevalent malignancy worldwide with a total of 28720 estimated new cases and ranks the fifth common cause resulting in male cancer death in USA (Siegel et al, 2012). Genome integrity and DNA damages have shed light on the mechanisms that concealed in HCC development (Price et al, 2013). Hepatitis B virus is the most common environmental cause of HCC susceptibility (>80%) which usually leads to DNA damages (McKillop et al, 2006). Different DNA damages could be revised by multiple regulatory pathways involved in the DNA repair system, which is crucial for maintaining the integrity of genome and suppressing carcinogenesis (Smith et al, 2003). Mutations in BER component DNA repair genes are accompanied by amino acids substitution, which alter the functions of corresponding enzymes, and thereby damage the capability of the host to revise DNA damage and make it more susceptible to carcinogenesis (Miller et al, 2001)
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