ASSOCIATIONS BETWEEN CYTOCHROME P4502E1 GENOTYPE, MUTAGEN SENSITIVITY, CIGARETTE-SMOKING AND SUSCEPTIBILITY TO LUNG-CANCER

Cytochrome P4502E1 (CYP2E1) is involved in the metabolic activation of carcinogenic N-nitrosoamines. We therefore assessed the genotype freq uencies of PstI or RsaI CYP2E1 restriction fragment length polymorphis ms and another susceptibility marker, mutagen sensitivity, in 137 lung cancer cases (92 African American and 45 Mexican American) and 206 co ntrols (114 African American and 92 Mexican American) identified in a molecular epidemiological study of lung cancer, The CYP2E1 c1/c1 genot ype was found in 86.7% of Mexican American cases, 70.6% of Mexican Ame rican controls, 89.1% of African American cases and 86.8% of African A merican controls, By multivariate analysis, this genotype was found to be associated with a 14.0-fold increased risk of lung cancer in Mexic an Americans but not in African Americans; a 9.9-fold increased risk o f lung cancer in Mexican American former smokers, but not in non-smoke rs or current smokers; a 15-fold increased risk of lung cancer in Mexi can American males, but not in females, Patients with the susceptible genotype appeared to have developed cancer at an earlier age and with lower cigarette pack-year of exposure than did patients with the c1/c2 or c2/c2 genotypes, Stratified analysis suggested a greater than mult iplicative interaction between cigarette smoking and CYP2E1 c1/c1 geno type, although not statistically significant, The odds ratios (ORs) fo r the CYP2E1 c1/c1 genotype, cigarette smoking and both risk factors c ombined were 1.3, 6.7 and 16.3, respectively, The association between CYP2E1 c1/c1 genotype and pack-years of smoking followed the same patt ern, The interaction between mutagen sensitivity and CYP2E1 c1/c1 geno type was especially strong in former smokers (the ORs for the CYP2E1 c 1/c1 genotype, mutagen sensitivity and both risk factors combined were 3.9, 5.4 and 23.0, respectively), Therefore, the data suggest that in dividuals who lack a c2 allele might be at higher risk for developing lung cancer.