Association of Non-Steroidal Anti-Inflammatory Drugs, Genetic Risk, and Environmental Risk Factors with Incidence of Colorectal Cancer

SIMPLE SUMMARY: It remains unknown whether regular use of non-steroidal anti-inflammatory drugs (NSAIDs) could attenuate the impact of genetic risk and environmental risk factors on colorectal cancer (CRC). In the current study, we evaluated the association of NSAID use, genetic risk, and environmental risk factors with CRC incidence using data from a UK Biobank cohort. We found that regular use of NSAIDs was associated with a lower risk of CRC. Although there were no statistical interactions observed between NSAID use, environmental risk and genetic risk, regular NSAID use was still associated with lower CRC incidence among subjects with either high environmental risk or high genetic risk. Furthermore, low environmental risk was associated with lower CRC incidence among subjects with high genetic risk. These findings emphasized the importance of the chemopreventive effect of regular use of NSAIDs and controlling modifiable environmental risk factors to reduce CRC incidence, even among individuals with a moderate or high genetic risk of CRC. ABSTRACT: Regular use of non-steroidal anti-inflammatory drugs (NSAIDs) was associated with the lower risk of colorectal cancer (CRC). However, whether regular use of NSAIDs could attenuate the effect of genetic risk and environmental risk factors on CRC is unknown. We aimed to evaluate the association of NSAID use, genetic risk, and environmental risk factors with CRC. Using data from a UK Biobank, a Cox proportional hazards model was performed to estimate the risk of CRC according to NSAID use, polygenic risk score, and environmental risk factors. Regular use of NSAIDs was associated with a 36.0% lower risk of CRC. No statistically significant interaction was observed between NSAID use and the genetic risk score (p = 0.190), and between NSAID use and the environmental risk score (p = 0.740). However, regular NSAID use was still associated with lower CRC incidence among subjects with either high environmental risk or high genetic risk. Furthermore, the genetic and environmental risk of CRC were additives. These findings appear to support the chemopreventive effect of regular NSAID use. Furthermore, controlling of modifiable environmental risk factors can reduce the CRC risk, especially among individuals with a moderate or high genetic risk of CRC.