Multiple observational studies and large, randomized controlled trials indicate that non-steroidal anti-inflammatory drugs (NSAIDs) strongly reduce risk for colorectal neoplasms. The strengths of these findings suggest that NSAIDs may so mask various risk factor-colorectal neoplasm associations, that they may be undetectable among NSAID users. Temporal changes and between-population differences in regular NSAID use prevalence may account for some of the inconsistencies in reported findings for risk factor-colorectal neoplasm associations. We investigated whether associations of known colorectal cancer risk factors with colorectal adenoma differed by non-aspirin NSAID use using pooled data from 3 colonoscopy-based case-control studies of incident, sporadic colorectal adenoma conducted in Minnesota, North Carolina, and South Carolina between 1991 and 2002. Participants (n=789 cases, 2,035 polyp-free controls) provided risk factor data prior to colonoscopy. The multivariable-adjusted odds ratios (OR) (95% confidence intervals [CI]) for those in the highest relative to the lowest quartiles of exposure, by regular non-aspirin NSAID non-use/use, respectively, were 1.57 (CI 0.96, 2.55) vs. 1.22 (CI 0.40, 3.70) for total fat, 1.37 (CI 0.86, 2.18) vs. 0.78 (CI 0.26, 2.35) for saturated fat, 0.92 (CI 0.67, 1.26) vs. 1.31 (CI 0.62, 2.76) for total calcium, 0.88 (CI 0.64, 1.22) vs. 1.38 (CI 0.65, 2.93) for total fruits and vegetables, 1.05 (CI 0.73, 1.50) vs. 0.73 (CI 0.33, 1.62) for red and processed meats, and 0.84 (CI 0.65, 1.10) vs. 0.97 (CI 0.54,1.75) for physical activity. For current smokers relative to never smokers, the ORs (CIs) among regular non-NSAID users/non-users were 2.88 (CI 2.20, 3.77) vs. 1.64 (CI 0.85, 3.17), respectively, and for those who were obese relative to those who were normal weight, they were 1.65 (CI 1.27, 2.16) vs. 1.20 (CI 0.70, 2.04). The associations of age, height, and intakes of alcohol, dietary fiber, and total folate with adenoma did not substantially differ according to NSAID use.

These findings suggest that regular non-aspirin NSAID use may mask, beyond simple confounding, associations of various risk factors with colorectal adenoma, suggesting that differential proportions of regular NSAID users between study populations may explain some inconsistencies in reported risk factor-colorectal neoplasm associations, and support routinely assessing such associations stratified by regular non-aspirin NSAID use.

Citation Format: Sobia Mujtaba, Roberd M. Bostick. Differences in risk factor-colorectal adenoma associations according to non-steroidal anti-inflammatory drug use [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2302. doi:10.1158/1538-7445.AM2017-2302