Dietary intake is thought to influence cancer risk, progression, and survival; however, the biological mechanisms underlying these effects in the context of tumour genetics remain poorly defined. This project aims to investigate how diet interacts with systemic metabolism and common cancer driver pathways to influence cancer outcomes at population scale.
The primary research questions are:
(i) How do dietary patterns associate with circulating metabolite profiles linked to cancer risk and prognosis?
(ii) Do genetic alterations affecting the PI3K-AKT signalling pathway modify the metabolic and clinical impact of dietary exposures?
(iii) Can integrated genetic-metabolomic signatures identify subgroups of patients with differential disease progression and survival?
Using Tier 3 data from the UK Biobank, this study will integrate plasma metabolomics, tumour genomic information, nutritional and pharmacological treatment regimens where available, and longitudinal clinical outcomes. First, associations between dietary intake, drug treatment, and metabolite profiles relevant to lipid, glucose, and inflammatory metabolism will be characterised in individuals with and without cancer. Second, genetic analyses will assess whether variation in genes within the PI3K-AKT pathway, including PIK3CA, modifies dietary- and/or drug treatment-metabolite relationships and cancer outcomes. Finally, these integrated profiles will be related to disease progression and survival to identify metabolic biomarkers of risk and prognosis.
The scientific rationale is that dietary and/or drug exposures exert their effects through systemic metabolic pathways that intersect with oncogenic signalling networks such as PI3K-AKT. By combining dietary, metabolomic, genetic, and clinical data in a large prospective cohort, this research aims to define genetically informed metabolic contexts in which diet or common medications may influence cancer progression, supporting a precision nutrition framework
