The first 2 authors contributed equally to this work.
Early Detection and Diagnosis
Alcohol dehydrogenase 1C*1 allele is a genetic marker for alcohol-associated cancer in heavy drinkers†
Article first published online: 14 NOV 2005
Copyright © 2005 Wiley-Liss, Inc.
International Journal of Cancer
Volume 118, Issue 8, pages 1998–2002, 15 April 2006
How to Cite
Homann, N., Stickel, F., König, I. R., Jacobs, A., Junghanns, K., Benesova, M., Schuppan, D., Himsel, S., Zuber-Jerger, I., Hellerbrand, C., Ludwig, D., Caselmann, W. H. and Seitz, H. K. (2006), Alcohol dehydrogenase 1C*1 allele is a genetic marker for alcohol-associated cancer in heavy drinkers. Int. J. Cancer, 118: 1998–2002. doi: 10.1002/ijc.21583
Part of this study was presented as Poster of Distinction at the Digestive Disease Week 2003 in Orlando, USA (Gastroenterology 2003;124:A546).
- Issue published online: 15 FEB 2006
- Article first published online: 14 NOV 2005
- Manuscript Accepted: 28 JUL 2005
- Manuscript Received: 12 MAY 2005
- University of Erlangen-Nürnberg. Grant Number: 01.03.14.1.
- alcohol dehydrogenase;
- genetic risk;
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.