The role of diet, nutrition and adiposity on colorectal cancer development. (360G-Wellcome-318478_Z_24_Z)

Globally the incidence of colorectal cancer (CRC) is increasing. Dietary factors impact CRC risk, however, it is not clear how two diets; a low-sugar (less than 5% total energy intake (TEI)) or a low-carbohydrate (less than 10% TEI) diet, affect CRC development. Randomized controlled trials (RCT) could provide valuable insight into the nature of this relationship. However, RCTs are often impractical due to timescale, cost, ethics, and the inherent complexity of nutrition research. I propose using existing data/samples from a previously conducted dietary intervention RCT manipulating sugar and carbohydrate intake in 60 healthy individuals. I hypothesize that manipulating carbohydrate and sugar content will lead to biological changes in blood and adipose tissue that influence CRC risk. I will measure these biological changes using serum proteomics and bulk RNA-sequencing, next I will identify genetic instruments to proxy for the altered molecular traits in Mendelian randomization (MR) analyses. MR is a genetic epidemiologic method that can be used to determine whether there is causal relationship between an exposure (e.g., an altered molecular trait) and an outcome (e.g., CRC). This will allow me to establish whether these dietary patterns are beneficial or detrimental to CRC development, and guide further research into underlying mechanisms.