Association of Nonsteroidal Anti-Inflammatory Drugs with Colorectal Cancer by Subgroups in the VITamins and Lifestyle (VITAL) Study.

Abstract

There is substantial evidence that use of NSAIDs reduces the risk of colorectal cancer, but no subgroup has been identified for which the chemoprevention effect outweighs the risk of side effects. We tested the interaction between NSAID use and multiple risk factors on colorectal cancer risk in the VITAL cohort. A total of 73,458 individuals ages 50 to 76 years completed a questionnaire between 2000 and 2002, and 674 incidental colorectal cancer cases were identified through 2010. In stratified analysis, high use of any type of NSAIDs (4+ days/week for 4+ years) was statistically significantly associated with a lower risk of colorectal cancer across all subgroups stratified by sex, body mass index, physical activity, smoking, alcohol intake, screening, and dietary factors. There was a suggestion of stronger associations among men, obese individuals, and heavier drinkers; however, none of these tests for interaction reached statistical significance. The associations were almost identical for subjects with higher overall colorectal cancer risk scores [HR, 0.62; 95% confidence interval (CI), 0.49-0.79] and those with lower risk scores (HR, 0.61; 95% CI, 0.42-0.88). Differential effects by cancer subsites and stages were tested. NSAID use was associated with a greater risk reduction of proximal colon cancer versus distal (P for difference = 0.06) and distant stage versus local (P for difference = 0.04). The association between high use of NSAIDs and colorectal cancer risk does not differ significantly among subgroups. Our results suggest that NSAIDs have a generally beneficial role in colorectal cancer prevention, largely unmodified by other exposures.