Influence of NQO1, ALDH2, and CYP2E1 genetic polymorphisms, smoking, and alcohol drinking on the risk of lung cancer in Koreans

We investigated the association of genetic polymorphisms of NQO1, ALDH2, CYP2E1, and the combined genotype of these genes on lung cancer risk, and also evaluated the association after stratification by cumulative smoking amounts and alcohol drinking levels. The case-control study was performed in 387 lung cancer patients and 387 age- and sex-matched cancer-free controls. Direct interview was conducted and the genotypes of NQO1, ALDH2, and CYP2E1 were investigated using PCR-RFLP or 5'-nuclease activity assay. The proportion of individuals with occupational history of mining was significantly higher in cases than in controls. The risk of lung cancer was significantly lower in light-drinkers (<108 g/week) than non-drinkers. The NQO1 Pro/Ser + Ser/Ser genotype showed an increased risk for lung cancer with a marginal significance (OR = 1.35, 95% CI = 0.99-1.86) compared with NQO1 Pro/Pro genotype. In heavy-smokers, the combination of NQO1 Pro/Ser + Ser/Ser and CYP2E1 c1/c1 genotype was associated with a significantly increased risk for lung cancer (OR = 2.25, 95% CI = 1.14-4.43) compared with those of NQO1 Pro/Pro and CYP2E1 c1/c2 + c2/c2 genotype. We found a significant interaction between alcohol drinking level and the CYP2E1 genotype (P = 0.0227). Our result suggests that the risk of lung cancer is affected by smoking, alcohol drinking, and the genetic polymorphism of NQO1. In particular, genetic polymorphisms for NQO1, CYP2E1, and ALDH2 synergistically with cumulative smoking amounts and alcohol drinking levels interact in the carcinogenesis of lung cancer in Koreans.