ANALYSIS OF CYTOCHROME P450-2E1 GENETIC POLYMORPHISMS IN RELATION TO HUMAN LUNG-CANCER

Human cancer risk assessment using molecular genetic techniques is a r apidly emerging field. Many studies suggest that both inherited and ac quired genetic predispositions play an important role in carcinogenesi s. Cytochrome P450 (CYP) 2E1 is involved in the metabolic activation o f N-nitrosamines and other low molecular weight compounds. A recently described genetic polymorphism of CYP2E1 [Dral restriction fragment le ngth polymorphism (RFLP)] has been associated with an increased risk o f lung cancer in Japanese. We have assessed the allelic frequency of t hree RFLPs (Pstl, Rsal, and Dral) in African-Americans (n = 109), Cauc asian Americans (n = 153), and octogenarian Japanese (n = 42), and als o in a United States case-control study of lung cancer (histologically confirmed lung cancer, n = 58; controls, n = 56; total, n = 114). The relationship of the CYP2E1 Dral Polymorphism to other CYP2E1 polymorp hisms (Pstl and Rsal RFLP) was examined. The allelic frequency of the Dral C minor allele for all subjects was 0.09 in Caucasians, 0.09 in A frican-Americans, and 0.31 in Japanese. In the case-control study of l ung cancer, no association of the CYP2E1 Dral genotype with lung cance r was found (odds ratio, 1.57; 95% confidence interval, 0.59-4.18). Co mparison after discordant CYP2E1 genotypes suggests the presence of di fferent haplotypes in Americans and Japanese. These results indicate t hat the CYP2E1 Dral RFLP is probably not a cancer risk factor in Unite d States Caucasian or African-Americans, although statistical power is limited given the low frequency of the CYP2E1 Dral C minor alleles.