Differences in Risk Factor: Colorectal Adenoma Associations According to Aspirin/Non-Steroidal Anti-Inflammatory Drug Use

Abstract

Introduction: Colorectal cancer (CRC) is the second leading cause of death from cancer in the United States. Adenomatous polyps are the precursor lesions for most cases of CRC. Compared to low risk adenomas (LRA), high risk adenomas (HRA) and advanced adenomas carry a higher risk of progression to CRC. There are several modifiable and non-modifiable factors that are associated with lower or higher risk of colorectal adenomas and CRC. Multiple observational studies and large, randomized controlled trials indicate that aspirin and nonsteroidal anti-inflammatory drugs (NSAIDs) strongly reduce risk for colorectal neoplasms. Furthermore, results from some studies indicate that aspirin and NSAID use may in fact mask the associations of known risk factors for colorectal neoplasia with colorectal neoplasms such that they may be undetectable among aspirin or NSAID users. We investigated the associations of known risk factors for colorectal neoplasia with LRA and HRA or advanced neoplasia, and whether these risk factor-colorectal neoplasm associations differ by aspirin and/or NSAID use. Methods: Using pooled data from three case-control studies of incident, sporadic colorectal adenoma conducted in Minnesota, North Carolina, and South Carolina between 1991 and 2002, we compared cases with HRA/advanced adenomas (n=570) and those with LRA (n=96) (as defined by the U.S. Multi-Society Task-Force on Colorectal Cancer) to controls (n=2,035). Participants provided risk factor data prior to colonoscopy. We used unconditional logistic regression to calculate the multivariable-adjusted odds ratios (OR) (95% confidence intervals [CI]) for those in the higher relative to the lower quantiles of exposure, and stratified the associations by aspirin and/or NSAID use. Results: The OR and 95% CI for associations of selected risk factors with LRA and with HRA or advanced neoplasia, which differed by aspirin and/or NSAID use are presented in Tables 1 and 2 respectively.Table: Table. Multivariable - adjusted associations of selected risk factors with low risk adenomas, stratified by aspirin and/or NSAID useTable: Table. Multivariable - adjusted associations of selected risk factors with high risk/advanced adenomas, stratified by aspirin and/or NSAID useConclusion: Our findings suggest that the potent anti-inflammatory effects of aspirin and NSAIDs may mask various risk factor-colorectal adenoma associations, particularly among those with LRAs, and support routinely assessing such associations stratified by aspirin and/or NSAID use to facilitate further understanding of the etiology of colorectal neoplasms and how to potentially prevent them.