Protective Effect of NSAIDs on Cancer and Influence of COX-2 C

Purpose: Inhibition of COX-2 enzymes is a frequently suggested mechanism for the beneficial effects of NSAIDs on carcinogenesis. The aim of this study was to explore the role of cumulative NSAID use on four common nonskin related cancers and modification by COX-2 G^-765C genotype. Patients and methods: 7621 participants of The Rotterdam Study were included. In a mean follow up period of 10 years, 720 colorectal, lung, breast or prostate cancers occurred. Cumulative NSAID use was calculated per NSAID class. Individual associations of NSAID use and COX-2 G^-765C genotype on cancer risk were explored with Cox' proportional hazard models. Next, the association of NSAIDs and cancer stratified by COX-2 genotype was studied. Finally, the effect of combinations of NSAID use and COX-2 genotype on survival times was investigated. Conclusion: Our results confirm the protective effect of NSAID use on colorectal cancer. Individuals diagnosed with colorectal cancer who carry a COX-2 C^-765 allele and are on NSAIDs have an increased survival in comparison to non-users with the wild type ^-765.