RsaI polymorphism at the cytochrome P4502E1 locus and risk of hepatocellular carcinoma

Abstract

Background - CYP2E1, the coding gene for the ethanol inducible cytochrome P4502E1, is polymorphic at the RsaI restriction site in the 5' flanking region. The mutant allele c2 has a higher transcriptional activity than the wild-type gene cl. P4502E1 catalyses the activation of several environmental carcinogens at a rate that is increased, if only moderately, by longterm ethanol intake. Aims - To establish the distribution of CYP2E1 RsaI polymorphism in patients with hepatocellular carcinoma and to evaluate its possible role in the multifactorial pathogenesis of this tumour. Subjects - 101 (84 males) patients with hepatocellular carcinoma and 178 (128 males) healthy controls of the same ethnic (white) and Spanish origin. Methods - After extraction of DNA from white blood cells, alleles cl and c2 of CYP2E1 were identified by restriction fragment length polymorphism (RFLP) with endonuclease RsaI. Results - Homozygous c1c1: 90 patients and 169 controls; heterozygous c1c2: 11 and 9; homozygous c2c2: none (nonsignificant difference). C2 allele frequencies: 0.055 in patients, 0.025 in controls (non-significant difference) and 0.108 in the 37 patients who had drunk more than 50 g of ethanol/day (p=0.0035, odds ratio versus controls: 4.67; 95% confidence limits 1.57 to 13.81). Conclusion - The carrier state of one copy of the c2 CYP2E1 gene increases the risk of hepatoma in previously regular ethanol users with chronic liver disease.