title: Alcohol and colorectal cancer: the role of alcohol dehydrogenase 1C polymorphism.
abstract: BACKGROUND
  Chronic alcohol consumption is a risk factor for colorectal cancer. Animal experiments as well as genetic linkage studies in Japanese individuals with inactive acetaldehyde dehydrogenase leading to elevated acetaldehyde concentrations following ethanol ingestion support the hypothesis that acetaldehyde may be responsible for this carcinogenic effect of alcohol. In Caucasians, a polymorphism of alcohol dehydrogenase 1C (ADH1C) exists resulting in different acetaldehyde concentrations following ethanol oxidation.
  
  
  METHODS
  To evaluate whether the association between alcohol consumption and colorectal tumor development is modified by ADH1C polymorphism, we recruited 173 individuals with colorectal tumors diagnosed by colonoscopy and 788 control individuals without colorectal tumors. Genotyping was performed using genomic DNA extracted from whole blood followed by polymerase chain reaction.
  
  
  RESULTS
  Genotype ADH1C*1/1 was more frequent in patients with alcohol-associated colorectal neoplasia compared to patients without cancers in the multivariate model controlling for age, gender, and alcohol intake (odds ratio = 1.674, 95% confidence interval = 1.110-2.524, 2-sided p from Wald test = 0.0139). In addition, the joint test of the genetic effect and interaction between ADH1C genotype and alcohol intake (2-sided p = 0.0007) indicated that the difference in ADH1C*1 polymorphisms between controls and colorectal neoplasia is strongly influenced by the alcohol consumption and that only individuals drinking more than 30 g ethanol per day with the genotype ADH1C*1/1 had an increased risk for colorectal tumors.
  
  
  CONCLUSIONS
  These data identify ADH1C homozygosity as a genetic risk marker for colorectal tumors in individuals consuming more than 30 g alcohol per day and emphasize the role of acetaldehyde as a carcinogenic agent in alcohol-related colorectal carcinogenesis.
authors.affiliation: Department of Gastroenterology, University of Lübeck, Lübeck, Germany.
authors.forename: Nils
authors.initials: N
authors.lastname: Homann
authors.forename: Inke R
authors.initials: IR
authors.lastname: König
authors.forename: Michael
authors.initials: M
authors.lastname: Marks
authors.forename: Monika
authors.initials: M
authors.lastname: Benesova
authors.forename: Felix
authors.initials: F
authors.lastname: Stickel
authors.forename: Gunda
authors.initials: G
authors.lastname: Millonig
authors.forename: Sebastian
authors.initials: S
authors.lastname: Mueller
authors.forename: Helmut K
authors.initials: HK
authors.lastname: Seitz
mesh_terms: D000079:Acetaldehyde / Q000378:metabolism; D000236:Adenoma / Q000235:genetics*; D000328:Adult; D000368:Aged; D000426:Alcohol Dehydrogenase / Q000235:genetics* / Q000378:metabolism; D000428:Alcohol Drinking / Q000009:adverse effects*; D002277:Carcinoma / Q000235:genetics*; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000378:metabolism; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D012307:Risk Factors
chemical_list: C420272:ADH1C protein, human; D000426:Alcohol Dehydrogenase; D000079:Acetaldehyde