Amitay EL, et al. - Given the inverse association of regular use of aspirin and nonsteroidal anti-inflammatory drugs (NSAIDs) for a longer period with colorectal cancer (CRC) risk, researchers investigated the associations with respect to the molecular pathological subtypes of CRC. According to findings, risk reduction of CRC subtypes varied following regular use of NSAIDs and aspirin. They noted a strong correlation of regular use of NSAIDs and aspirin with risk reduction of microsatellite instability (MSI)-high CRC without Kirsten rat sarcoma viral oncogene homolog gene (KRAS) or B-Raf proto-oncogene serine/threonine kinase (BRAF) mutation.

Methods

• Researchers analyzed 2,444 cases with a first diagnosis of CRC and 3,130 healthy control individuals from a German population-based case control study.
• They performed an analysis of tumor tissue samples for major molecular pathological features: MSI, CpG island methylator phenotype, BRAF mutation, and KRAS mutation.
• Standardized interviews were conducted to obtain information on past and current use of NSAIDs, including aspirin.
• Adjusted odds ratios and 95% confidence intervals were calculated using multinomial logistic regression models.
• Two-sided statistical tests were performed.

Results

• They noted a reduction in CRC risk in correlation with regular use of NSAIDs, if tumors were MSS, BRAF wildtype, or KRAS wildtype.
• For MSI-high, BRAF-mutated, or KRAS-mutated CRC, less clear and mostly not statistically significant association of regular NSAID use with CRC risk reduction was evident.
• Regular use of NSAIDs was correlated with a much stronger risk reduction in the absence of BRAF or KRAS mutations but not with KRAS- or BRAF-mutated MSI-high CRC in more specific analyses on MSI-high CRC (P_{heterogeneity} < 0.001).
• Similar results were noted for just aspirin use.