Abstract
OBJECTIVE: Because multiple observational studies and large, randomized controlled trials indicate that NSAIDs strongly reduce the risk of colorectal neoplasms, we investigated whether NSAID use masks associations of various other risk factors with colorectal neoplasms. MATERIALS AND METHODS: Using pooled data from three case-control studies of incident, sporadic colorectal adenoma (pooled n=789 cases, 2035 polyp-free controls), using multivariable logistic regression, we investigated various risk factor-colorectal adenoma associations stratified by NSAID use. RESULTS: Example multivariable-adjusted odds ratios [95% confidence intervals (CI)] for those in the highest relative to the lowest quartiles of exposure, by regular nonaspirin NSAID nonuse/use, respectively, were 1.57 (95% CI: 0.96-2.55) versus 1.14 (95% CI: 0.37, 3.49) for total fat, 1.37 (95% CI: 0.86-2.18) versus 0.70 (95% CI: 0.23-2.25) for saturated fat, 0.93 (95% CI: 0.68-1.28) versus 1.30 (95% CI: 0.61-2.75) for calcium, 0.89 (95% CI: 0.64-1.23) versus 1.38 (95% CI: 0.65-2.94) for total fruits and vegetables, and 0.85 (95% CI: 0.65-1.11) versus 0.94 (95% CI: 0.52-1.71) for physical activity. For current versus never smokers, the odds ratios (95% CIs) among regular non-NSAID users/nonusers were 2.91 (95% CI: 2.22-3.82) versus 1.75 (95% CI: 0.90-3.41), respectively, and for those who were obese versus those who were normal weight, they were 1.67 (95% CI: 1.28-2.17) versus 1.19 (95% CI: 0.69-2.04), respectively. CONCLUSION: Our findings suggest that regular nonaspirin NSAID use may mask, beyond simple confounding, associations of major risk factors with colorectal adenoma, and support routinely assessing such associations stratified by regular nonaspirin NSAID use.