Sequence variations in DNA repair gene XPCis associated with lung cancer risk in a Chinese population: a case-control study

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Abstract
Background: The nucleotide excision repair (NER) protein, xeroderma pigmentosum C (XPC), participates in recognizing DNA lesions and initiating DNA repair in response to DNA damage. Because mutations inXPCcause a high risk of cancer in XP patients, we hypothesized that inherited sequence variations inXPCmay alter DNA repair and thus susceptibility to cancer.Methods: In this hospital-based case-control study, we investigated fiveXPCtagging, common single nucleotide polymorphisms (tagging SNPs) in 1,010 patients with newly diagnosed lung cancer and 1,011 matched cancer free controls in a Chinese population.Results: In individual tagging SNP analysis, we found that rs3731055AG+AAvariant genotypes were associated with a significantly decreased risk of lung adenocarcinoma [adjusted odds ratio (OR), 0.71; 95% confidence interval (CI), 0.56–0.90] but an increased risk of small cell carcinomas [adjusted OR, 1.79; 95% CI, 1.05–3.07]. Furthermore, we found that haplotypeACCCAwas associated with a decreased risk of lung adenocarcinoma [OR, 0.78; 95% CI, 0.62–0.97] but an increased risk of small cell carcinomas [OR, 1.68; 95% CI, 1.04–2.71], which reflected the presence of rs3731055Aallele in this haplotype. Further stratified analysis revealed that the protective effect of rs3731055AG+AAon risk of lung adenocarcinoma was more evident among young subjects (age ≤ 60) and never smokers.Conclusion: These results suggest that inherited sequence variations inXPCmay modulate risk of lung cancer, especially lung adenocarcinoma, in Chinese populations. However, these findings need to be verified in larger confirmatory studies with more comprehensively selected tagging SNPs.