Background/Airns: Cytochrome P450 2E1 (CYP2EI) is the only enzyme that rnetabolizes very low doses of N-nitrosodimethylamine (NDMA) and is characterized by its ethanol inducibility. Recently, it has been shown in an animal-experimental study that NDMAinduced hepatocarcinogenes was facilitated by chronic alcohol ingestion. CYP2E1 expression in human beings was reported to be about 10 times higher in genotype c2/c2 than in genotype cl/cl. Bacause CYP2El gene expression is the highest in the liver, we hypothesized that the polymorphi:;m of CYP2E1 may affect the risk of hepatocellular carcinoma (HCC), especially in patients with chronic alcohol consumption. METHODS: We enrolled 46 HCC patients and 32 age-sex-matcied healthy controls without liver disease or cancer in any other organ. The genotypes in the 5-flanking region of CYP2E1 gene were determined by restriction fragment length polymorphisms using two endonucleases: PstI and RsaI. RESULTS: The frequencies of genotype A (cl/cl), B (cl/c2) and C (c2/c2) were 56.5%, 39.1%, 4.4% in HCC patients, and 62.5%, 28.1%, 4.4% in controls, regiectively. The frequency of allele c2 was 23.9% in HCC patients and 23.4% in control, re.;pectively. The difference in the frequencies of both CYP2E1 genotyps and alleles was not statistically significant between the HCC patients and controls. The HCC patients with a history of ckonic alcohol ingestion were more likely to carry genotype B and C than in patients without such tii.;tory, even though the differences are not statistically significant (p=0.077). CONCLUSIONS: Although polymorphisms of CYP2E1 gene is not a major genetic risk factor for the development of HCC, it might increase the risk of HCC in patients with chronic HBV or HCV infection and chronic alcohol consumption. Further study to test this bypothesis on a large number of patients and on patients of different ethnic groups is warranted.