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Alcohol dehydrogenase 1C*1 allele is a genetic marker for alcohol‐associated cancer in heavy drinkers
Author(s) -
Homann Nils,
Stickel Felix,
König Inke R.,
Jacobs Arne,
Junghanns Klaus,
Benesova Monika,
Schuppan Detlef,
Himsel Susanne,
ZuberJerger Ina,
Hellerbrand Claus,
Ludwig Dieter,
Caselmann Wolfgang H.,
Seitz Helmut K.
Publication year - 2005
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.21583
Subject(s) - alcohol dehydrogenase , allele , alcohol , genetics , genetic marker , medicine , alcohol consumption , cancer , biology , oncology , environmental health , gene , biochemistry
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. © 2005 Wiley‐Liss, Inc.