Effect modification of the alcohol – colorectal cancer association

Abstract

Introduction: Alcohol consumption is an established risk factor for colorectal cancer (CRC). However, while studies have consistently reported elevated risk of CRC among heavy drinkers, associations at moderate levels of alcohol consumption are less clear. We conducted a meta-analysis of 16 studies of CRC to examine the shape of the alcohol-CRC association, investigate potential effect modifiers of the association between alcohol consumption and CRC, and examine differential effects of alcohol consumption by cancer anatomic site and cancer stage. Methods: We collected information on alcohol consumption for 13,248 cases and 14,430 controls from 5 case-control and 11 nested case-control studies of CRC. We compared adjusted logistic regression models with linear and restricted cubic splines to select a model that best fit the association between alcohol consumption and CRC. Study-specific results were pooled using fixed-effects meta-analysis. Potential effect modifiers were evaluated using multiplicative interaction terms. Results were also stratified by cancer anatomic site and stage. Results: Compared to non-/occasional drinking, light/moderate drinking (up to 2 drinks/day) was associated with a decreased risk of CRC (OR: 0.92, 95% CI: 0.87-0.98, p<0.007), while very heavy drinking (more than 3 drinks/day) was associated with an increased risk (OR: 1.26, 95% CI: 1.11-1.42, P<0.001). While the risk associated with very heavy alcohol consumption was elevated among men (OR: 1.33, p<0.001) and among distal colon (OR: 1.41, p<0.001) and rectal cancers (OR 1.53, p<0.001), the protective effect of light/moderate drinking was observed across both sexes and all tumor sites and there was no evidence of significant interaction in any of the stratified analyses. Discussion: These results support a J-shaped association between alcohol consumption and CRC risk. This overall pattern, particularly the protective effect of light/moderate drinking, was not significantly modified by other CRC risk factors or tumor site.