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

Background & Aims: 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). Methods: 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. Results: The c1/c1 genotype of CYP2E1, detected by Pstl or Rsal 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 Dral polymorphism of CYP2E1 or for the GSTM1-null genotype. Conclusions: Polymorphisms of CYP2E1 may play an important role in cigarette smoking-related hepatocarcinogenesis.