Association of DNA repair gene XRCC1 and lung cancer susceptibility among nonsmoking Chinese women

Nonsmokers who develop lung cancer provide a good model for investigating the effect of genetic polymorphisms. XRCC1 is one of the major DNA repair proteins involved in the base-excision repair pathway. XRCC1 gene variations may lead to lower DNA repair capacity and thus confer inherited predisposition to cancer risk. To address this question in more detail, we conducted a hospital-based case-control study consisting of 55 lung cancer cases and 74 cancer-free controls matched on age and ethnicity among nonsmoking Chinese women. We analyzed five coding single-nucleotide polymorphisms in the XRCC1 gene: Agr194Trp, Arg280His, Arg399Gln, Pro206Pro, and Gln632Gln. Polymerase chain reaction-restriction fragment length polymorphism was used for genotyping. Carriers of the variant T-allele of Arg194Trp had a lower lung cancer risk than carriers of CC genotypes [odds ratio (OR)=0.46, 95% confidence interval (CI)=0.22-0.96, P=0.04], and carriers of the variant G-allele of Pro206Pro were at almost fourfold (OR=3.93, 95%CI=1.47-10.52, P=0.004) higher risk of lung cancer than carriers of the AA genotype. Furthermore, we observed that individuals with haplotype 1(194T-206A-280G-399G-632G) had decreased risk of lung cancer (OR=0.51, 95%CI= 0.27-0.97, P=0.04) and subjects with haplotype 2 (194C-206G280G-399G- 632A) had almost a threefold increased risk of lung cancer (OR=3.01, 95%CI=1.01-8.92, P=0.04). These findings further suggest that the polymorphisms XRCC1 Arg194Trp and Pro206Pro or the haplotype encompassing the variant alleles may contribute to susceptibility of lung cancer in a Chinese population.