Associations of Lys939Gln and Ala499Val polymorphisms of theXPCgene with cancer susceptibility: A meta-analysis

Abstract

XPC polymorphisms may alter DNA repair capacity, thus leading to genetic instability and carcinogenesis. Numerous studies have investigated the associations of XPC Lys939Gln (rs2228001) and Ala499Val (rs2228000) polymorphisms with cancer susceptibility; however, the findings are inconclusive. We searched literature from MEDLINE and EMBASE for eligible publications that assessed the associations between these two polymorphisms and cancer risk. We also assessed genotype-mRNA expression correlation data from HapMap for rs2228001 and rs2228000 in normal cell lines derived from 270 subjects with different ethnicities. The final analysis included 62 published studies of 25,708 cases and 30,432 controls for the Lys939Gln and 34 studies with 14,877 cases and 17,888 controls for the Ala499Val. Overall, Lys939Gln was significantly associated with an increased overall cancer risk (Gln/Gln vs. Lys/Lys: OR 5 1.16, 95% CI 5 1.07 2 1.25, p < 0.001; recessive model: OR 5 1.14, 95% CI 5 1.06 2 1.22, p < 0.001; dominant model: OR 5 1.06, 95% CI 5 1.01 2 1.11, p 5 0.015 and Gln vs. Lys: OR 5 1.07, 95% CI 5 1.03 2 1.10, p < 0.001) and further stratifications showed an increased risk for bladder, lung and colorectal cancer, Asian populations and population-based studies. Likewise, Ala499Val was also significantly associated with an increased overall cancer risk (Val/Val vs. Ala/Ala: OR 5 1.21, 95% CI 5 1.07 2 1.36, p 5 0.003 and recessive model: OR 5 1.20, 95% CI 5 1.08 2 1.34, p 5 0.001) and further stratification showed an increased risk for breast and bladder cancer, particularly in Asian populations. Interestingly, significantly correlation between XPC genotypes and mRNA expression was found only for Asian populations as well. Despite some limitations, this meta-analysis established some solid statistical evidence for an association between XPC polymorphisms and cancer risk, which warrants further validation in single large studies.

Association Between Six Genetic Polymorphisms and Colorectal Cancer: A Meta-Analysis

“…In the present study, we perform meta-analyses to evaluate the contribution of the six polymorphisms to CRC susceptibility in different populations. The goal of our study is to summary the contribution of rs12917 and rs2308321 of MGMT, rs1229984 of ADH1B, and rs4880 of SOD2, and to update the meta-analyses for rs2228001 of XPC (He et al, 2013) and rs1801282 of PPARG (Xu et al, 2010).…”

Association Studies of ERCC1 Polymorphisms with Lung Cancer Susceptibility: A Systematic Review and Meta-Analysis

“…After screening and reviewing articles for study eligibility, 113 articles were excluded due to review articles or non case-control studies, overlapped participants, failure to report genotype distribution data, and other reasons described previously [14] (Figure 1). For example, among the 15 studies concerning ERCC1 rs11615 polymorphism [4], [15]–[28], 5 were reported by Yin JY et al [18], [25]–[28],.…”

“…However, our results did not reveal any significant association between either of polymorphisms and lung cancer risk. As previously published [14], [32], we used information from HapMap and SNPexp online tool to further estimate whether expression levels of ERCC1 transcript correlate with genotypes of these two polymorphisms. Given subjects in our meta-analysis were from Chinese and Caucasian populations, we performed the correlation analyses for CHB (Chinese), CEU (Caucasian), and a combination of these two populations, respectively.…”

Association of XPC Gene Polymorphisms with Colorectal Cancer Risk in a Southern Chinese Population: A Case-Control Study and Meta-Analysis

“…Upon recognition of damaged DNA, the XPC complex can interact with xeroderma pigmentosum group A (XPA) or TFIIH to enable the downstream steps of NER, including excision and restoration of DNA [16]. There are three widely investigated common polymorphisms in the XPC gene, XPC rs2228001 A > C, rs2228000 C > T [8], and a poly (AT) deletion/insertion on intron 9 [17]. The XPC rs2228001 A > C polymorphism, an A-to-C transition in exon 15, leads to a substitution of glutamine for lysine in codon 939 (Lys939Gln), while rs2228000 C > T polymorphism is a C-to-T transition in exon 8, resulting in the replacement of alanine with valine in codon 499 (Ala499Val) [18].…”

“…To date, at least 102 single nucleotide polymorphisms (SNPs) have been reported in the coding region of this gene [7]. Of these coding region SNPs, XPC Lys939Gln (rs2228001 A > C) and Ala499Val (rs2228000 C > T) polymorphisms have been foci of interest for their potential function, as well as association with the risk of various types of cancer, including breast cancer, lung cancer, bladder cancer, and colorectal cancer (CRC) [8]. A number of studies have been conducted to explore the association between these two polymorphisms and CRC susceptibility in different ethnicities which have shown some promising results [9,10,11].…”