Relatonship Between Genetic Polymorphism Of Metabolizing Enzymes And Tobacco-related Lung Cancer

Objective: To investigate the relations of metabolizing enzymes' genetic polymorphism with lung cancer risk, especially in heavy smokers.Methods: We conducted a case-control study, detected CYP1A1, 2A6, 2D6, 2E1 and GSTM1 genotype of 180 patients with lung cancer and 224 controls by using PCR-based genotype assays.Results: CYP1A1 variant allele, CYP2D6 wild allele, CYP2E1 A genotype and GSTMl-null genotype were found to be associated with lung cancer (OR= 1.5-1.58; p<0.05 ) , especially CYP1 Al with squamous cell carcinoma (SCC) , small cell carcinoma (SCLC) ; CYP2D6 with SCC; CYP2E1 with adenocarcinoma (AC) . The relationship between CYP2A6 polymorphism and risk of lung cancer couldn't be found in this study. The individuals who carry GSTMl-null genotype and at least one of the CYP1A1, CYP2D6, CYP2E1 'in risk' genotype have an 2.24-5.09 fold increased risk of lung cancer. To investigate the joint effect of smoking and different metabolizing enzymes' genotype, the heavy smokers have a 2-3 fold increased risk of lung cancer than the non-smokers who carry the same genotype of metabolizing enzymes. The heavy smoker who carry (GSTM1 (-) /CYP2D6 (w/w + w/m) /2E1 (A) ) or (GSTM1 (-) /CYP1A1 (w/m + m/m) /2D6 (w/w + w/m) ) or (GSTM1 (-) /CYP1A1 (w/m + m/m ) /2E1 (A) ) have an obviously increased risk of lung cancer than those don't carry these kind of genotype (OR=9.85 95%CI=2.3~45.71). Conclusions: The individuals who carry the 'in risk' genotype of metabolizing enzymes have an increase risk of lung cancer. Moreover, the risk of lung cancer is associated with cumulative cigarette dose. The heavy smokers who carry the 'in risk' genotype of metabolizing enzymes were more sensitive to the tobacco carcinogen. The multiple detection of metabolizing enzymes could help us to find the group who has the highest risk of lung cancer, providing a guide to decrease the incidence rate of lung cancer.