Colorectal cancer (CRC) is a major public health burden. Diet is potentially modifiable, yet studies of specific nutrients and CRC often conflict, with differences in direction and magnitude. These inconsistencies may reflect population differences, how diet is measured, and residual confounding. Independent evidence from a large cohort is needed to produce more reliable, generalisable conclusions.
Using the UK Biobank, we will examine associations of CRC incidence and mortality with nutrient-related exposures relevant to CRC. Initial priority will be given to six nutrients selected in advance based on existing evidence (folate, iron, polyunsaturated fatty acids, vitamin B1, vitamin B12 and vitamin D), with additional analyses of closely related nutrient measures where appropriate within the same project scope. Objectives are to: (1) test whether associations are reproduced in an independent cohort; (2) assess whether results differ across key characteristics (e.g., sex, age, adiposity) to understand heterogeneity; and (3) use heterogeneity patterns to interpret conflicting literature and prioritise nutrients for follow-up. If emerging evidence or data availability suggests minor refinements, this priority list may be updated within the same project scope and documented in project reporting.
This work will strengthen population-level evidence while reducing reliance on a single data source. The UK Biobank’s large sample size, long-term follow-up, linkage to cancer and death records, and rich information on lifestyle and health factors support more consistent comparisons within one framework and help identify informative sources of heterogeneity, improving interpretability and generalisability. By clarifying for whom and under what circumstances findings are most consistent, it can support clearer risk communication and better-informed prevention research, and help prioritise targets for later mechanistic and interventional studies.