Alcohol consumption and distinct molecular pathways to colorectal cancer.

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.