Circulating insulin-like growth factor I (IGF-I) is positively associated with the risks of colorectal, breast, and prostate cancer, but evidence for other less common cancers is limited. In this study, we investigated associations between serum IGF-I concentrations and incidence of less common cancers in the UK Biobank study. To enable comparison of effect estimates, and as positive controls, both common and less common cancer sites (total 30) were included in an outcome-wide analysis. Data from 394,388 cancer-free participants in the UK Biobank study were analyzed. Multivariable adjusted Cox proportional hazards models were used to determine associations between baseline serum IGF-I concentrations and cancer incidence, using repeated IGF-I measurements from up to 14,149 participants to correct for regression dilution bias. Higher IGF-I concentration was associated with increased risks of thyroid cancer [HR per 5 nmol/L higher concentration 1.18; 95% confidence interval (CI), 1.01-1.37] in addition to colorectal (HR, 1.08; 95% CI, 1.03-1.13), breast (HR, 1.11; 95% CI, 1.07-1.15), and prostate cancer (HR, 1.08; 95% CI, 1.05-1.12), and reduced risks of ovarian and liver cancer. Mean follow-up was 6.9 years and the possibility that the observed associations may be influenced by reverse causality bias cannot be excluded. Additional nominally significant associations with malignant melanoma, multiple myeloma, oral cancer, and esophageal squamous cell carcinoma did not survive correction for multiple testing. Studies with longer follow-up and pooled analyses are needed to further assess how broad the role of IGF-I is in cancer development.
Mediating mechanisms linking anthropometric, lifestyle and dietary risk factors with cancer risk
The mediating mechanisms linking anthropometric and lifestyle risk factors with cancer development and survival remain unclear. We aim to investigate the potential mediating roles of metabolic factors (including biomarkers and intermediate conditions and diseases) on the association between risk factors (e.g. fat mass, diet, physical activity) and subsequent cancer diagnosis, death and survival by cancer type. The proposed project aims to understand the mechanisms that underpin the association of risk factors with cancer development and progression, which is consistent with UK Biobank's mission of health-related research that is in the interest of the public good. In the first stage of this project we will run prospective analyses to assess the associations of potential risk factors with risk of, and death from, specific cancers. If there are sufficient cases and available information on tumour characteristics, we will split tumours into subtypes. We will also assess the association between the potential risk factors and each of the possible mediators, as well as the prospective associations between the mediators and cancer risk. Finally, we will estimate the mediation effects of the individual mediators in the associations between risk factors and cancer risk. We intend to include all participants of the UK Biobank cohort.
|Lead investigator:||Dr Aurora Perez-Cornago|
|Lead institution:||University of Oxford|