LUNG-CANCER RISK IN RELATION TO THE CYP2E1 RSA-I GENETIC-POLYMORPHISMAMONG AFRICAN-AMERICANS AND CAUCASIANS IN LOS-ANGELES-COUNTY

Genetic polymorphisms in the activation or detoxication of carcinogens , such as those in tobacco smoke, may produce differences in individua l susceptibility to lung cancer. The cytochrome P450 CYP2E1 is an enzy me involved in the metabolism of nitrosamines in tobacco smoke. A poly morphism of CYP2E1 detectable by the restriction enzyme Rsa I may be f unctionally important becaue it is located in a putative binding site for the transcription factor HNF-1 and has been associated with higher levels of CYP2E1 transcription. It is conceivable that this CYP2E1 Rs a I polymorphism might contribute to differences in susceptibility to lung cancer. We conducted a case-control study of patients with incide nt lung cancer and population controls in Los Angeles County to examin e the association between the CYP2E1 Rsa I polymorphism and lung cance r risk among African-Americans and Caucasians. Samples of white blood cell DNA sufficient for determination of the CYP2E1 Rsa I genotype by a polymerase chain reaction-based assay were obtained from 341 cases a nd 706 controls with data on lifetime smoking history. No subjects wer e homozygous for the CYP2E1 Rsa I rare c2 allele. The rare c2 allele w as not associated with an increased risk of lung cancer (adjusted odds ratio, OR = 0.72; 95% confidence interval, CI = 0.35-1.46). Among the population controls the percentage of subjects carrying the rare c2 a llele was lower (p = 0.002) among African-Americans (2%) compared with Caucasians (8%). However, the association between the CYP2E1 Rsa I ge notype and lung cancer risk did not differ between ethnic groups. Ther e was no important association between the CYP2E1 Rsa I genotype and l ung cancer risk in analyses stratified by cell-type, smoking history, gender, occupational asbestos exposure, and dietary intake of antioxid ants vitamin C, vitamin E or betacarotene. Due to the low frequency of the c2 allele in these populations, larger studies would be necessary to rule out a modest association between the CYP2E1 Rsa I polymorphis m and lung cancer risk.