Alcohol Consumption and the Risk of Colorectal Cancer for Mismatch Repair Gene Mutation Carriers

Abstract

Background: People with germline mutation in one of the DNA mismatch repair (MMR) genes have increased colorectal cancer risk. For these high-risk people, study findings of the relationship between alcohol consumption and colorectal cancer risk have been inconclusive.Methods: 1,925 MMR gene mutations carriers recruited into the Colon Cancer Family Registry who had completed a questionnaire on lifestyle factors were included. Weighted Cox proportional hazard regression models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI) for the association between alcohol consumption and colorectal cancer.Results: Colorectal cancer was diagnosed in 769 carriers (40%) at a mean (SD) age of 42.6 (10.3) years. Compared with abstention, ethanol consumption from any alcoholic beverage up to 14 g/day and >28 g/day was associated with increased colorectal cancer risk (HR, 1.50; 95% CI, 1.09-2.07 and 1.69; 95% CI, 1.07-2.65, respectively; P_trend = 0.05), and colon cancer risk (HR, 1.78; 95% CI, 1.27-2.49 and 1.94; 95% CI, 1.19-3.18, respectively; P_trend = 0.02). However, there was no clear evidence for an association with rectal cancer risk. Also, there was no evidence for associations between consumption of individual alcoholic beverage types (beer, wine, spirits) and colorectal, colon, or rectal cancer risk.Conclusions: Our data suggest that alcohol consumption, particularly more than 28 g/day of ethanol (∼2 standard drinks of alcohol in the United States), is associated with increased colorectal cancer risk for MMR gene mutation carriers.Impact: Although these data suggested that alcohol consumption in MMR carriers was associated with increased colorectal cancer risk, there was no evidence of a dose-response, and not all types of alcohol consumption were associated with increased risk. Cancer Epidemiol Biomarkers Prev; 26(3); 366-75. ©2016 AACR.

Figure 1. Hazard ratios for associations between alcohol consumption and the risk of colon, rectum, and colorectal cancer for DNA mismatch repair gene germline mutation carriers by sex

Abbreviations: HR, hazard ratio; CI, confidence interval; PY, person-years All models were multivariable and adjusted for country (categorical, time-fixed), education (categorical, time-fixed l), ascertainment (binary, time-fixed), at age 20 (categorical, time-fixed), diabetes status (binary, time-varying), regular physical activity (binary, time-varying), and smoking status (categorical, time-varying) Models for women were additionally adjusted for number of live births (categorical, time-varying), and years of hormonal contraceptive use (categorical, time-varying) Models for beer were additionally adjusted for average daily ethanol intake from wine (binary, time-varying) and from spirits (binary, time-varying) Models for wine were additionally adjusted for average daily ethanol intake from beer (binary, time-varying) and from spirits (binary, time-varying) Models for sake were additionally adjusted for average daily ethanol intake from beer (binary, time-varying) and from wine (binary, time-varying)