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 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. CONCLUSIONS: Polymorphisms of CYP2E1 may play an important role in cigarette smoking-related hepatocarcinogenesis.[1]References
- Cytochrome P450 2E1 and glutathione S-transferase M1 polymorphisms and susceptibility to hepatocellular carcinoma. Yu, M.W., Gladek-Yarborough, A., Chiamprasert, S., Santella, R.M., Liaw, Y.F., Chen, C.J. Gastroenterology (1995) [Pubmed]
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