Gastroenterology

Gastroenterology

Volume 109, Issue 4, October 1995, Pages 1266-1273
Gastroenterology

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

https://doi.org/10.1016/0016-5085(95)90587-1Get rights and content

Abstract

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.

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    Supported by grants DOH-H7707, DOH-H7903, DOH-H8003, DOH-H8103, and DOH-H8203 from the Department of Health, Executive Yuan; grant NSC83-0412-B-002-256 from the National Science Council of the Republic of China; and grant ESO 5116 from the National Institutes of Health.

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