title: Cytochrome P450 2E1 variable number tandem repeat polymorphisms and             health risks: a genotype-phenotype study in cancers associated with drinking and/or             smoking.
abstract: Cytochrome P450 2E1 (CYP2E1) is one of the main enzymes involved in the oxidation of ethanol and in the transformation of a number of potentially dangerous compounds. It has various polymorphic sites, one of which is a variable number tandem repeat (VNTR) polymorphism previously described in the 5'-flanking region. The aim of this study was to investigate the genotype-phenotype association between CYP2E1 VNTR polymorphisms and risky health habits in healthy subjects and to analyze the associations between these polymorphisms with drinking- and/or smoking-related cancers. We analyzed 166 healthy subjects by genotyping for the CYP2E1 VNTR polymorphism associated with drinking and/or smoking habits by the more sensitive restriction fragment length polymorphism-polymerase chain reaction (RFLP-PCR) method, using the NlaIV restriction enzyme. Sixty cases of pancreatic adenocarcinoma (PA) and 66 with hepatocellular carcinoma (HCC), were also genotyped. Statistical analysis was carried out to investigate the genotype-phenotype associations and to compare certain genotypes and cancer. We found 7 genotypes both in the healthy subjects and patients. The A1/A1 genotype was observed to be mainly associated with non-drinkers and -smokers (87.5 and 75.0%, respectively); moreover it was never found in the PA or HCC patients. Conversely, a weak association between A2/A3 with smokers (45.8%) and A4/A4 with drinkers (53.9%) was detected. In addition, the A4/A4 genotype was found to be significantly associated to PA [odds ratio (OR)=3.25; 95% confidence interval (CI) 1.21-7.50]. Our data demonstrate that certain CYP2E1 VNTR genotypes are associated with drinking and/or smoking habits; consequently, they may contribute either to the decreased or increased risk of developing drinking- and/or smoking-related cancers. In particular, we hypothesize that the A1/A1 VNTR genotype may have a protective role against drinking- and/or smoking-related cancers, and that A4/A4 may be a high-risk genotype during the early stages of cancer.
authors.affiliation: Department of Molecular and Biomolecular Sciences and Technologies                     (STEMBIO), Section of Cellular Biology, University of Palermo, I-90128                     Palermo, Italy.
authors.forename: Irene
authors.initials: I
authors.lastname: Catanzaro
authors.forename: Flores
authors.initials: F
authors.lastname: Naselli
authors.forename: Marghereth
authors.initials: M
authors.lastname: Saverini
authors.forename: Antonio
authors.initials: A
authors.lastname: Giacalone
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Montalto
authors.forename: Fabio
authors.initials: F
authors.lastname: Caradonna
mesh_terms: D000328:Adult; D000428:Alcohol Drinking / Q000235:genetics*; D006528:Carcinoma, Hepatocellular / Q000235:genetics; D016022:Case-Control Studies; D019392:Cytochrome P-450 CYP2E1 / Q000235:genetics*; D005260:Female; D056726:Genetic Association Studies / Q000379:methods*; D020022:Genetic Predisposition to Disease; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics; D008297:Male; D018598:Minisatellite Repeats; D016017:Odds Ratio; D010190:Pancreatic Neoplasms / Q000235:genetics; D011110:Polymorphism, Genetic; D012150:Polymorphism, Restriction Fragment Length; D012307:Risk Factors; D012309:Risk-Taking; D012907:Smoking / Q000235:genetics*; D055815:Young Adult
chemical_list: D019392:Cytochrome P-450 CYP2E1