Several dietary patterns have been associated with colorectal cancer (CRC) risk but underlying mechanisms are not fully understood. Also, evidence is lacking on the consistency of dietary guidelines for overall health and CRC prevention given that it is not feasible to have an optimal diet for every disease. Furthermore, metabolomic profiling has not been widely assessed with respect to CRC risk. Metabolomics is uniquely suited to assess metabolic responses to dietary stimuli, given that it is situated downstream to all the other "omics". Building on prior work in hypothesis-driven dietary patterns and CRC prevention, the researchers seek to fill these knowledge gaps by proposing to: 1) use a standardized methodology to compare the best diet for overall health with the best diet for CRC prevention, and further determine if any associations of dietary patterns with CRC prevention are mediated by mechanisms involving inflammation and insulin; 2) determine metabolites that may mediate the association of dietary intake with CRC risk. The researchers will utilize two large prospective cohort studies, the Nurses' Health Study (NHS) and the Health Professionals Follow-up Study (HPFS), in which dietary and nondietary data have been collected every 2 to 4 years among 173,230 women and men over the last ≥30 years, with ≥3,400 CRC cases and ≥43,800 all-cause deaths. This integrated interrogation of dietary patterns and metabolomics data will inform the design of guidelines for healthful lifestyles that are optimized for CRC prevention.
