Cytochrome P450 2E1 and glutathione S-transferase M1 polymorphisms and susceptibility to hepatocellular carcinoma.

Abstract

Genetic polymorphisms in enzymes involved in carcinogen metabolism have been found to influence susceptibility to cancer. The aim of this study was to examine whether cytochrome P450 2E1 (CYP2E1) and/or glutathione S-transferase M1 (GSTM1) genetic polymorphisms were related to susceptibility to hepatocellular carcinoma (HCC). Genotyping of CYP2E1 and GSTM1 was performed using the polymerase chain reaction on peripheral white blood cell DNA from 30 patients with HCC and 150 controls nested in a cohort study. The c1/c1 genotype of CYP2E1, detected by PstI or RsaI digestion, was found in 83.3% of patients with HCC and in 63.3% of controls (P = 0.034). Homozygosity for the c1/c1 genotype significantly increased the risk of developing HCC in cigarette smokers (P = 0.001) but posed no increased risk in those who never smoked. The HCC risk associated with cumulative exposure to cigarette smoke was also more striking in individuals who carried the c1/c1 genotype. Habitual alcohol drinking modified the HCC risk of cigarette smoking among those with the c1/c1 genotype. No association with the risk of HCC was observed for the DraI polymorphism of CYP2E1 or for the GSTM1-null genotype. Polymorphisms of CYP2E1 may play an important role in cigarette smoking-related hepatocarcinogenesis.