Effects of diets on risks of cancer and the mediating role of metabolites

Research on the association between dietary adherence and cancer risk is limited, particularly concerning overall cancer risk and its underlying mechanisms. Using UK Biobank data, we prospectively investigate the associations between adherence to a Mediterranean diet (MedDiet) or a Mediterranean-Dietary Approaches to Stop Hypertension Diet Intervention for Neurodegenerative Delay diet (MINDdiet) and the risk of overall and 22 specific cancers, as well as the mediating effects of metabolites. We show significant negative associations of MedDiet and MINDdiet adherence with overall cancer risk, robust across 14 and 13 specific cancers, respectively. Using a sequential analysis incorporating Cox regression, elastic net and gradient boosting, we identify 10 metabolites associated with overall cancer risk. Mediation results indicate these metabolites play crucial, independent and cumulative roles in the association between diet adherence and cancer risk. These findings deepen understanding of connections between diet, metabolites, and cancer development.