Lack of association of cytochrome P450 2E1 genetic polymorphisms with the risk of human hepatocellular carcinoma.

The iso-enzyme pattern of cytochrome P450 was shown to be related to the development of chemically induced hepatocellular carcinoma (HCC) in rats, which is accelerated by chronic alcohol ingestion. Our study was designed to investigate the association of cytochrome P450 2E1 (CYP2E1) genetic polymorphisms with the susceptibility to HCC in humans with and without chronic alcohol ingestion. We enrolled 171 male patients (108 Korean and 63 Japanese) with HCC and 31 age- and sex-matched healthy Korean subjects with no evidence of liver disease or cancer in any organ. Genotypes in the 5'-flanking region of the CYP2E1 gene were determined by restriction fragment length polymorphisms using 2 endonucleases: Pst I and Rsa I. Allelic frequencies in the CYP2E1 5'-flanking region in the Korean control population were 83.5% and 16.5% for allele c1 and c2, respectively. The frequencies of genotypes with the c2 allele (c1/c2 and c2/c2) were compared with those of genotypes without c2 (c1/c1) among HCC patients and controls, according to the pattern of alcohol consumption. There was no significant association between HCC risk and genotypes c1/c2 and c2/c2 either in all HCC patients or in HCC patients of different ethnic groups. Habitual drinkers with HCC, especially among Koreans, were more likely to carry genotype c1/c2 and c2/c2 (odds ratio = 3.0) than non-habitual drinkers (odds ratio = 1.2); however, the difference was not statistically significant. Even when patients were restricted to those without hepatitis B surface antigen and antibodies against hepatitis C virus but with a history of chronic alcohol ingestion, there was still no increased risk of HCC in those with genotypes c1/c2 and c2/c2. We conclude that there is a lack of association of the polymorphisms of CYP2E1 with the risk of HCC in humans.