Single Nucleotide Polymorphisms In Carcinogen-Metabolizing And DNA Repair Genes And Susceptibility To Lung Cancer

DNA repair has an essential role in protecting the genome from damage by endogenous and environmental agents. Polymorphisms in DNA repair genes may be associated with difference in the repair capacity and may influence an individual's risk of cancer. We therefore conducted a case-control study to assess the relationship between polymorphisms in DNA repair genes XPA, XPC, XPD, XPG, XRCC1, XRCC3 and NBS1 and lung cancer risk.A total of 868 primary lung cancer cases and 887 healthy controls were recruited and frequency-matched on age, gender and smoking status. Genotypes were determined by PCR-RFLP, PCR-SSCP and DNA sequencing techniques. Odds ratios (ORs) and their 95% confidence intervals (CIs) were computed to estimate the risk of lung cancer for each genotype. All statistical tests were two-side tests.We found that polymorphisms in XPC, XPD, XPG, XRCC1, and NBS1 but not XRCC3 and XPA, were associated with risk of lung cancer. The XPC intron 9 PAT -/-and intron 11 -5CC genotypes were associated with increased risk of lung cancer compared with the respective PAT +/+ or PAT +/- genotype (OR = 1.55, 95% CI = 1.05-2.28) and -5AC or -5AA genotype (OR =1.82, 95% CI = 1.23-2.68). Subjects homozygous for the XPD 312Asn/Asn genotype had a substantially increased risk of lung cancer (OR = 4.79, 95% CI = 1.00-22.81) compared with subjects homozygous for the 312Asp/Asp genotype. Stratification analysis revealed that the increased risk was mainly confined to lung squamous cell carcinoma, with the OR for the 312Asn/Asn genotype being 9.96 (95% CI = 1.85-53.66). The XPG 1104His/His genotype was weakly but significantly associated with lung cancer (OR = 1.40, 95% CI = 1.06-1.84, P = 0.02). The risk for the 1104His/His genotype appeared to be more...