Associations between polymorphisms of the XPC gene and lung cancer susceptibility: a meta-analysis

Xeroderma pigmentosum complementation group C (XPC) gene plays a critical role in DNA damage recognition, and its functional single nucleotide polymorphisms (SNPs) may alter DNA repair capacity and cancer susceptibility. Numerous epidemiological studies have investigated the associations between XPC Lys939Gln and Ala499Val polymorphisms and lung cancer susceptibility, but the conclusions are inconclusive. We searched three electronic databases (MEDLINE, EMBASE and EBSCO) for eligible publications and performed a meta-analysis assessing the associations between XPC Lys939Gln and Ala499Val polymorphisms and lung cancer risk. We also analysed the genotype-mRNA expression correlation using the data of HapMap phase II release 23 with 270 individuals from 4 ethnicities for exploring biological plausibility of our findings. We included ten published studies of 3,882 cases and 5,219 controls for Lys939Gln, and five studies with 2,605 cases and 3,329 controls for Ala499Val. When all studies were pooled, we found a significantly increased overall lung cancer risk for Lys939Gln polymorphism (recessive model: OR = 1.14, 95 % CI = 1.01-1.29, P = 0.218 for heterogeneity). Stratification analysis also showed a higher lung cancer risk in Asian populations (recessive model: OR = 1.26, 95% CI = 1.04-1.52, P = 0.263 for heterogeneity). Interestingly, we found significant correlation between Lys939Gln genotypes and XPC mRNA expression for Asian populations as well. However, we did not observe any association between Ala499Val polymorphism and overall lung cancer risk, nor in further stratification analysis. This meta-analysis suggests that XPC Lys939Gln polymorphism may contribute to lung cancer risk, which needs further validation in single larger studies.