Abstract
Research on the association between dietary adherence and cancer risk is limited, particularly concerning overall cancer risk and its underlying mechanisms. Using the 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. Here we show significant negative associations of MedDiet and MINDDiet adherence with overall cancer risk. These associations remain robust across 14 and 13 specific cancers, respectively. Then, a sequential analysis, incorporating Cox regression, elastic net and gradient boost models, identify 10 metabolites associated with overall cancer risk. Mediation results indicate that these metabolites play a crucial role in the association between adherence to a MedDiet or a MINDDiet and cancer risk, independently and cumulatively. These findings deepen our understanding of the intricate connections between diet, metabolites, and cancer development.