title: Alcohol consumption and distinct molecular pathways to colorectal cancer.
abstract: High alcohol consumption is related to colorectal cancer (CRC). Our objective was to study associations between alcohol consumption and risk of CRC according to characteristics of aetiological pathways: the chromosomal instability (CIN) and the microsatellite instability (MIN) pathway. We classified CIN+ tumours (tumours with either a truncating APC mutation, an activating K-ras mutation or overexpression of p53), MIN+ tumours (tumours lacking hMLH1 expression) and CIN- /MIN- tumours (tumours without these defects). In the Netherlands Cohort Study on diet and cancer, 120852 men and women, aged 55-69 years, completed a questionnaire on risk factors for cancer at baseline (1986). Case-cohort analyses were conducted using 573 CRC cases with complete data after 7 x 3 years of follow-up, excluding the first 2 x 3 years. Adjusted incidence rate ratios (RR) and 95 % confidence intervals (CI) were estimated. Compared with abstaining, alcohol consumption of >or=30 g/d was positively associated with the risk of CRC irrespective of genetic or molecular aberrations present, although statistical significance was not reached (RR 1 x 35 (95 % CI 0 x 9-2 x 0) for the CIN+ tumours, RR 1 x 59 (95 % CI 0 x 4-5 x 8) for the MIN+ tumours and RR 1.15 (95 % CI 0 x 5-2 x 7) for the CIN- /MIN- tumours). Beer, wine and liquor consumption were, independent of their alcoholic content, not consistently associated with the risk of CRC within the defined subgroups. In conclusion, our results indicate that a daily alcohol consumption of >or=30 g is associated with an increase in risk of CRC, independent of the presence or absence of the studied characteristics of different aetiological pathways.
authors.affiliation: Nutrition and Toxicology Research Institute Maastricht (NUTRIM), Department of Epidemiology, University Maastricht, 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: Stefan
authors.initials: S
authors.lastname: de Vogel
authors.forename: Piet A
authors.initials: PA
authors.lastname: van den Brandt
authors.forename: R Alexandra
authors.initials: RA
authors.lastname: Goldbohm
authors.forename: Matty P
authors.initials: MP
authors.lastname: Weijenberg
mesh_terms: D000368:Aged; D000428:Alcohol Drinking / Q000009:adverse effects* / Q000453:epidemiology; D043171:Chromosomal Instability; D015179:Colorectal Neoplasms / Q000453:epidemiology / Q000209:etiology* / Q000235:genetics; D004812:Epidemiologic Methods; D005260:Female; D017491:Genes, APC; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D053842:Microsatellite Instability; D008875:Middle Aged; D009154:Mutation; D009426:Netherlands / Q000453:epidemiology