CYTOCHROME P4502E1 (CYP2E1) GENETIC-POLYMORPHISM IN A CASE-CONTROL STUDY OF GASTRIC-CANCER AND LIVER-DISEASE

Cytochrome P4502E1 (CYP2E1) activates carcinogenic N-nitrosamines, ben zene, urethane and other low molecular weight compounds, This enzyme i s also inducible by ethanol, and metabolizes alcohol. A restriction fr agment length polymorphism (RFLP) using the Rsa I restriction enzyme h as been identified in the CYP2E1 transcription regulatory region; rece nt studies suggest that this polymorphism may affect gene expression. We investigated the frequency of the Rsa I RFLP in a Japanese populati on in relation to gastric cancer and liver disease susceptibility. The frequency of this polymorphism was determined in 150 gastric cancer, 16 hepatocellular cancer, 48 liver cirrhosis and 203 benign gastric di sease (controls) patients. This preliminary study shows no association of the specific genotype with gastric cancer in all subjects (odds ra tio = 1.04, 95% CI = 0.74-3.08 for the heterozygote and 0.57, 95% CI = 0.22-1.50 for the homozygous rare allele, respectively), To further c onfirm this lack of association, an age and gender matched case-contro l study should be performed. Separately, there was no association of t he Rsa I RFLP with hepatocellular carcinoma (p = 0.911), but there was a suggested difference between the non-viral associated liver cirrhos is patients and control patients. Thus, this polymorphism may be relat ed to ethanol metabolism and consequential liver diseases in a Japanes e population.