CYP2A13, CYP2A6, and the Risk of Lung Adenocarcinoma in a Japanese Population

Abstract

Both cytochrome P450 (CYP) 2A6 and CYP2A13 are involved in the metabolic activation of tobacco-specific N-nitrosamines (TSNAs). Some kinds of TSNAs induce lung adenocarcinoma in laboratory animals. Thus, polymorphisms of CYP2A6 and CYP2A13 genes may be important as genetic factors of lung cancer, particularly lung adenocarcinoma. We genotyped 179 patients with lung cancer and 183 controls for CYP2A6 gene deletion-type and CYP2A13 C3375T polymorphisms by polymerase chain reaction-based techniques on DNA prepared from peripheral blood. In addition, a questionnaire was used to collect demographic, lifestyle and other information from each subject. Unconditional logistic regression was used to compute the odds ratios (ORs) and their 95% confidence intervals (95% CIs), with adjustments for several covariates found to be associated with risk. Compared with one or more copies of the T allele, the CYP2A13 CC genotype was associated with a substantially increased risk for lung adenocarcinoma (OR = 2.41, 95% CI = 1.03-6.28). Smokers with the CYP2A13 CC genotype showed significantly higher risk (OR = 4.88, 95% CI = 1.35-26.53) compared to non-smokers with possession at least one copy of the CYP2A13 T allele. Although our results indicate that the CYP2A13 gene may play a role in the development of lung adenocarcinoma, the risk for those individuals with single at-risk genotype of CYP2A13 C3375T polymorphism may not be so large. In future studies, analyses based on haplotypes are recommended to confirm the role of CYP2A13 gene in the development of lung adenocarcinoma.