Abstract
BackgroundReduced DNA repair capacities due to inherited polymorphisms may increase the susceptibility to cancers including gastric cancer. Previous studies investigating the association between Xeroderma Pigmentosum group C (XPC) gene polymorphisms and gastric cancer risk reported inconsistent results. We performed a meta-analysis to summarize the possible association.MethodsAll studies published up to January 2014 on the association between XPC polymorphisms and gastric cancer risk were identified by searching electronic databases PubMed, EMBASE, Cochrane library, and Chinese Biomedical Literature database (CBM). The association between XPC polymorphisms and gastric cancer risk was assessed by odds ratios (ORs) together with their 95% confidence intervals (CIs).ResultsSix studies with 1,355 gastric cancer cases and 2,573 controls were finally included in the meta-analysis. With respect to Lys939Gln polymorphism, we did not observe a significant association when all studies were pooled into the meta-analysis. When stratified by ethnicity, source of control, and study quality, statistical significant association was not detected in all subgroups. With respect to Ala499Val and PAT−/+polymorphisms, we also did not observe any significant association with gastric cancer risk in the pooled analysis.ConclusionsThis meta-analysis based on current evidences suggested that the XPC polymorphisms (Lys939Gln, Val499Arg, and PAT−/+) did not contribute to gastric cancer risk. Considering the limited sample size and ethnicity included in the meta-analysis, further larger scaled and well-designed studies are needed to confirm our results.Virtual SlidesThe virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1485880312555069
Highlights
Reduced DNA repair capacities due to inherited polymorphisms may increase the susceptibility to cancers including gastric cancer
Xeroderma Pigmentosum group C (XPC) binds to HR23B and forms the XPC-HR23B complex, which is involved in the DNA damage recognition and DNA repair initiation in the nuclear excision repair (NER) pathway [5,6,7], and the binding of XPC to damaged DNA is the rate-limiting step for NER [8]
It was reported that the variant alleles of the three polymorphisms in the XPC genes correlated with relatively high DNA adduct levels in lymphocyte DNA, indicating that these polymorphisms were associated with decreased DNA repair capacity [10,11]
Summary
Reduced DNA repair capacities due to inherited polymorphisms may increase the susceptibility to cancers including gastric cancer. Previous studies investigating the association between Xeroderma Pigmentosum group C (XPC) gene polymorphisms and gastric cancer risk reported inconsistent results. Among all the identified SNPs, three common polymorphisms have been extensively studied: (a) a substitution of alanine for valine in codon 499 (Ala499Val, rs2228000), in the interaction domain of XPC with hHRAD23; (b) an A to C transversion in exon 15 resulting in a lysine-to-glutamine transition at position 939 (Lys939Gln, rs2228001), located in the interaction domain with TFIIH; and (c) a poly AT region on intron 9 (PAT−/+). It was reported that the variant alleles of the three polymorphisms in the XPC genes correlated with relatively high DNA adduct levels in lymphocyte DNA, indicating that these polymorphisms were associated with decreased DNA repair capacity [10,11]. It was biologically reasonable to hypothesize a potential relationship between the XPC gene polymorphisms and cancer susceptibility
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