title: 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 c1. P4502E1 catalyses the activation of several environmental carcinogens at a rate that is increased, if only moderately, by longterm ethanol intake.
  
  
  OBJECTIVE
  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.
  
  
  METHODS
  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 c1 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 (non-significant 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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Service of Gastroenterology, San Carlos University Hospital, Department of Medicine, Medical School, Universidad Complutense, Madrid, Spain.
authors.forename: J M
authors.initials: JM
authors.lastname: Ladero
authors.forename: J A
authors.initials: JA
authors.lastname: Agúndez
authors.forename: A
authors.initials: A
authors.lastname: Rodríguez-Lescure
authors.forename: M
authors.initials: M
authors.lastname: Diaz-Rubio
authors.forename: J
authors.initials: J
authors.lastname: Benítez
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000437:Alcoholism / Q000150:complications*; D000483:Alleles; D006528:Carcinoma, Hepatocellular / Q000453:epidemiology / Q000235:genetics*; D016022:Case-Control Studies; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics*; D004706:Endodeoxyribonucleases; D005260:Female; D005796:Genes / Q000235:genetics*; D006801:Humans; D008113:Liver Neoplasms / Q000453:epidemiology / Q000235:genetics*; D008297:Male; D016017:Odds Ratio; D012150:Polymorphism, Restriction Fragment Length; D012307:Risk Factors; D013030:Spain / Q000453:epidemiology
chemical_list: D003577:Cytochrome P-450 Enzyme System; D004706:Endodeoxyribonucleases