title: Associations of Lys939Gln and Ala499Val polymorphisms of the XPC gene 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 = 1.16, 95% CI = 1.07 - 1.25, p < 0.001; recessive model: OR = 1.14, 95% CI = 1.06 - 1.22, p < 0.001; dominant model: OR = 1.06, 95% CI = 1.01 - 1.11, p = 0.015 and Gln vs. Lys: OR = 1.07, 95% CI = 1.03 - 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 = 1.21, 95% CI = 1.07 - 1.36, p = 0.003 and recessive model: OR = 1.20, 95% CI = 1.08 - 1.34, p = 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.
authors: Cancer Institute, Fudan University Shanghai Cancer Center, Shanghai, China.
authors: Jing
authors: J
authors: He
authors: Ting-Yan
authors: TY
authors: Shi
authors: Mei-Ling
authors: ML
authors: Zhu
authors: Meng-Yun
authors: MY
authors: Wang
authors: Qiao-Xin
authors: QX
authors: Li
authors: Qing-Yi
authors: QY
authors: Wei
mesh_terms: D002471:Cell Transformation, Neoplastic / Q000235:genetics; D004260:DNA Repair / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D009369:Neoplasms / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors
chemical_list: D004268:DNA-Binding Proteins; C086984:XPC protein, human
keywords: DNA repair; XPC; meta-analysis; polymorphism; susceptibility