Intake of red and processed meat, use of non-steroid anti-inflammatory drugs, genetic variants and risk of colorectal cancer; a prospective study of the Danish \"Diet, Cancer and Health\" cohort

Abstract

Red and processed meat have been associated with increased risk of colorectal cancer (CRC), whereas long-term use of non-steroid anti-inflammatory drugs (NSAIDs) may reduce the risk. The aim was to investigate potential interactions between meat intake, NSAID use, and gene variants in fatty acid metabolism and NSAID pathways in relation to the risk of CRC. A nested case-cohort study of 1038 CRC cases and 1857 randomly selected participants from the Danish prospective \"Diet, Cancer and Health\" study encompassing 57,053 persons was performed using the Cox proportional hazard models. Gene variants in SLC25A20, PRKAB1, LPCAT1, PLA2G4A, ALOX5, PTGER3, TP53, CCAT2, TCF7L2, BCL2 were investigated. CCAT2 rs6983267 was associated with risk of CRC per se (p<0.01). Statistically significant interactions were found between intake of red and processed meat and CCAT2 rs6983267, TP53 rs1042522, LPCAT1 rs7737692, SLC25A20 rs7623023 (pinteraction=0.04, 0.04, 0.02, 0.03, respectively), and use of NSAID and alcohol intake and TP53 rs1042522 (pinteraction=0.04, 0.04, respectively) in relation to risk of CRC. No other consistent associations or interactions were found. This study replicated an association of CCAT2 rs6983267 with CRC and an interaction between TP53 rs1042522 and NSAID in relation to CRC. Interactions between genetic variants in fatty acid metabolism and NSAID pathway and intake of red and processed meat were found. Our results suggest that meat intake and NSAID use affect the same carcinogenic mechanisms. All new findings should be sought replicated in independent prospective studies. Future studies on the cancer-protective effects of aspirin/NSAID should include gene and meat assessments.\n\nAuthor SummaryIntake of red and processed meat has been associated with risk of cancer and in particular colorectal cancer. However, the underlying biological mechanisms are only incompletely understood. Gene-environment interaction analysis may be used for identifying underlying mechanisms for e.g. meat carcinogenesis. In this work, we have analyzed the interaction between the intake of red and processed meat, use of non-steroid anti-inflammatory drugs (including the anti-carcinogenic drug aspirin) and genetic variants. Our results suggest that meat intake and non-steroid anti-inflammatory drug use affect the same carcinogenic mechanisms. These results need to be replicated in other cohort studies with lifestyle information. If replicated, these results may have future implications for developing new strategies for preventing colorectal cancer and other cancers that share similar pathways.