Diet, metabolic mediators, and cancer risk

Colorectal, breast, and prostate cancer account for nearly a third of all diagnosed cancers, and some dietary factors may influence risk. Moreover, circulating insulin-like growth factor-I (IGF-I) concentrations have been positively associated with risks of colorectal, breast, and prostate cancer, and IGF-I might mediate some diet-cancer associations. This thesis investigates the associations of dietary factors, IGF-I concentrations, and IGF-I related cancers among participants in the UK Biobank cohort.
Associations between intakes of food groups (438,453 participants) and macronutrients (11,815 participants) with IGF-I concentrations were explored. Intake of fish was positively associated with IGF-I concentrations, as was protein from dairy products; however, associations differed by dairy protein source in that milk and yogurt were positively associated with IGF-I concentrations whereas protein from cheese was not. Intakes of fibre and wholegrains were also positively associated with IGF-I concentrations.
The association between protein from all dairy products, milk, and cheese and colorectal, breast, and prostate cancer was explored among ~114,000 participants. Protein from all dairy products and milk were inversely associated with colorectal cancer risk, whereas a borderline positive association was observed for prostate cancer risk for men in the highest quartile of intake compared to those in the lowest quartile. IGF-I concentrations did not appear to explain these associations.
Prospective associations between carbohydrate types and sources and colorectal cancer were explored among ~114,000 participants. Non-free sugars and fibre from wholegrains were inversely associated with colorectal cancer risk. Evidence of heterogeneity by genetically predicted butyrate synthesis was observed; participants with high predicted butyrate and consuming higher wholegrains had a lower risk of colorectal cancer whereas no association was observed for those with low genetically predicted butyrate synthesis.
Finally, diet groups in relation to all cancer and common cancer types were investigated in prospective analyses of ~472,000 participants. In comparison to regular meat-eaters, low meat-eaters had lower risk of all cancer and colorectal cancer, fish-eaters had a lower risk of all cancer and prostate cancer, and vegetarians had a lower risk of all cancer, postmenopausal breast cancer, which may be due to their lower body mass index, and prostate cancer. Differences in IGF-I concentrations or free testosterone did not appear to mediate these associations.
In conclusion, research from this thesis supports dietary factors, such as dairy protein, being associated with IGF-I concentrations. However, whether these same dietary factors are positively associated with IGF-I related cancers remains unclear, suggesting other factors or mechanisms external to the IGF-I pathway. Potential novel findings suggest that wholegrain intake and colorectal cancer risk may vary by genetic factors for butyrate production and further research is needed to replicate and explore this further. Different diet groups may also be related to IGF-I related cancers; however, IGF-I concentrations did not mediate this association. Further research exploring mechanisms through and external to the IGF-I pathway is needed.

Keywords: diet
colorectal cancer
cancer
prostate cancer
short-chain fatty acids
breast cancer
epidemiology
insulin-like growth factor-I
Advisor: Pérez-Cornago, A
Key, T