title: Alcohol dehydrogenase 1C*1 allele is a genetic marker for alcohol-associated cancer in heavy drinkers.
abstract: Chronic alcohol consumption is associated with an increased risk for upper aerodigestive tract cancer and hepatocellular carcinoma. Increased acetaldehyde production via alcohol dehydrogenase (ADH) has been implicated in the pathogenesis. The allele ADH1C*1 of ADH1C encodes for an enzyme with a high capacity to generate acetaldehyde. So far, the association between the ADH1C*1 allele and alcohol-related cancers among heavy drinkers is controversial. ADH1C genotypes were determined by polymerase chain reaction and restriction fragment length polymorphism in a total of 818 patients with alcohol-associated esophageal (n=123), head and neck (n=84) and hepatocellular cancer (n=86) as well as in patients with alcoholic pancreatitis (n=117), alcoholic liver cirrhosis (n=217), combined liver cirrhosis and pancreatitis (n=17) and in alcoholics without gastrointestinal organ damage (n=174). The ADH1C*1 allele and genotype ADH1C*1/1 were significantly more frequent in patients with alcohol-related cancers than that in individuals with nonmalignant alcohol-related organ damage. Using multivariate analysis, ADH1C*1 allele frequency and rate of homozygosity were significantly associated with an increased risk for alcohol-related cancers (p<0.001 in all instances). The odds ratio for genotype ADH1C*1/1 regarding the development of esophageal, hepatocellular and head and neck cancer were 2.93 (CI, 1.84-4.67), 3.56 (CI, 1.33-9.53) and 2.2 (CI, 1.11-4.36), respectively. The data identify genotype ADH1C*1/1 as an independent risk factor for the development of alcohol-associated tumors among heavy drinkers, indicating a genetic predisposition of individuals carrying this genotype.
authors.affiliation: Department of Medicine I, University of Lübeck, Germany.
authors.forename: Nils
authors.initials: N
authors.lastname: Homann
authors.forename: Felix
authors.initials: F
authors.lastname: Stickel
authors.forename: Inke R
authors.initials: IR
authors.lastname: König
authors.forename: Arne
authors.initials: A
authors.lastname: Jacobs
authors.forename: Klaus
authors.initials: K
authors.lastname: Junghanns
authors.forename: Monika
authors.initials: M
authors.lastname: Benesova
authors.forename: Detlef
authors.initials: D
authors.lastname: Schuppan
authors.forename: Susanne
authors.initials: S
authors.lastname: Himsel
authors.forename: Ina
authors.initials: I
authors.lastname: Zuber-Jerger
authors.forename: Claus
authors.initials: C
authors.lastname: Hellerbrand
authors.forename: Dieter
authors.initials: D
authors.lastname: Ludwig
authors.forename: Wolfgang H
authors.initials: WH
authors.lastname: Caselmann
authors.forename: Helmut K
authors.initials: HK
authors.lastname: Seitz
mesh_terms: D000328:Adult; D000368:Aged; D000426:Alcohol Dehydrogenase / Q000235:genetics* / Q000378:metabolism*; D000428:Alcohol Drinking / Q000009:adverse effects* / Q000235:genetics*; D000483:Alleles; D005260:Female; D005770:Gastrointestinal Neoplasms / Q000209:etiology / Q000235:genetics; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006258:Head and Neck Neoplasms / Q000209:etiology / Q000235:genetics; D006801:Humans; D019656:Loss of Heterozygosity; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D012307:Risk Factors
chemical_list: D005819:Genetic Markers; D000426:Alcohol Dehydrogenase