title: Alcohol and the risk of colon and rectal cancer with mutations in the K-ras gene.
abstract: The first metabolite of alcohol, acetaldehyde, may trigger replication errors and mutations in DNA, which may predispose to developing colorectal cancer (CRC). In a prospective study on colon and rectal cancer, we investigated the following hypotheses: alcohol consumption is associated with an increased risk of mutations in the K-ras oncogene, and beer consumption is associated with an increased risk of G-->A mutations in this gene. Therefore, we studied the associations between consumption of alcohol and alcoholic beverages and the risk of CRC without and with specific K-ras gene mutations. In 1986, 120,852 men and women, aged 55-69 years, completed a questionnaire on risk factors for cancer. The case-cohort approach was used for data processing and analyses. After 7.3 years of follow-up, excluding the first 2.3 years, complete data from 4,076 subcohort members, 428 colon and 150 rectal cancer patients, were available for data analyses. Incidence rate ratios (RRs) and corresponding 95% confidence intervals (95% CIs) were estimated using Cox proportional hazards models. Compared to abstaining, a total alcohol consumption of 30.0 g/day and more was associated with the risk of colon and rectal cancer with and without a K-ras mutation in both men and women. Independent from alcohol intake, liquor consumption when compared to nonliquor consumption was associated with an increased risk of rectal cancer with a wild type K-ras in men (RR: 2.25, 95% CI: 1.0-5.0). Beer consumption was not clearly associated with the risk of colon and rectal tumors harboring G-->A mutations in the K-ras gene in men. This association could not be assessed in women because of sparse beer consumption. In conclusion, alcohol does not seem to be involved in predisposing to CRC through mutations in the K-ras gene, and specifically beer consumption is not associated with colon and rectal tumors harboring a G-->A mutation.
authors.affiliation: Nutrition and Toxicology Research Institute Maastricht (NUTRIM), Department of Epidemiology, University Maastricht, 6200 MD Maastricht, The Netherlands. Brenda.Bongaerts@epid.unimaas.nl
authors.forename: Brenda W C
authors.initials: BW
authors.lastname: Bongaerts
authors.forename: Anton F P M
authors.initials: AF
authors.lastname: de Goeij
authors.forename: Piet A
authors.initials: PA
authors.lastname: van den Brandt
authors.forename: Matty P
authors.initials: MP
authors.lastname: Weijenberg
mesh_terms: D000368:Aged; D000428:Alcohol Drinking / Q000009:adverse effects* / Q000453:epidemiology*; D000434:Alcoholic Beverages / Q000009:adverse effects; D001515:Beer / Q000009:adverse effects; D015331:Cohort Studies; D003110:Colonic Neoplasms / Q000453:epidemiology* / Q000235:genetics*; D003627:Data Interpretation, Statistical; D004032:Diet; D005091:Exons / Q000235:genetics; D005260:Female; D011905:Genes, ras / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D015233:Models, Statistical; D009426:Netherlands / Q000453:epidemiology; D016016:Proportional Hazards Models; D012004:Rectal Neoplasms / Q000453:epidemiology* / Q000235:genetics*; D012907:Smoking / Q000453:epidemiology