Genetic polymorphisms involved in carcinogen metabolism and DNA repair and lung cancer risk in a Japanese population

BACKGROUND: Several components of overall lung carcinogenesis, carcinogen metabolic and DNA repair pathways may be involved in individual genetic susceptibility to lung cancer. METHODS: We evaluated the role of cytochrome P450 (CYP) 1A1 rs4646903 and rs104894, glutathione S-transferase (GST) M1 and GSTT1 deletion polymorphisms, GSTP1 rs1695, x-ray repair, excision repair cross-complementing group 2 (ERCC2) rs13181, complementing defective in Chinese hamster 1 rs25487, and XRCC3 rs861539 in a case-control study comprising 462 lung cancer cases and 379 controls in a Japanese population. Unconditional logistic regression was used to assess the adjusted odds ratios (OR) and 95% confidence intervals (95% CI). RESULTS: CYP1A1 rs4646903 (OR = 1.72, 95% CI = 1.25-2.38), rs1048943 (OR = 1.40, 95% CI = 1.02-1.92), the GSTM1 deletion polymorphism (OR = 1.38, 95% CI = 1.01-1.89), GSTP1 rs1695 (OR =1.48, 95% CI = 1.04-2.11), ERCC2 rs13181 (OR = 1.89, 95% CI = 1.28-2.78), and Chinese hamster 1 rs25487 (OR = 1.54, 95% CI = 1.12-2.13) were associated with lung cancer risk whereas the GSTT1 deletion polymorphism and XRCC3 rs861539 were not. A pertinent combination of multiple "at-risk" genotypes of CYP1A1 rs4646903, the GSTM1 deletion polymorphism and ERCC2 rs13181 was at a 5.94-fold (95% CI = 2.77-12.7) increased risk of lung cancer. CONCLUSIONS: A pertinent combination of multiple at-risk genotypes may detect a high-risk group. Further studies are warranted to verify our findings.