Metabolomic landscape of overall and common cancers in the UK Biobank: A prospective cohort study

Information about the NMR metabolomics landscape of overall, and common cancers is still limited. Based on a cohort of 83,290 participants from the UK Biobank, we used multivariate Cox regression to assess the associations between each of the 168 metabolites with the risks of overall cancer and 20 specific types of cancer. Then, we applied LASSO to identify important metabolites for overall cancer risk and obtained their associations using multivariate cox regression. We further conducted mediation analysis to evaluate the mediated role of metabolites in the effects of traditional factors on overall cancer risk. Finally, we included the 13 identified metabolites as predictors in prediction models, and compared the accuracies of our traditional models. We found that there were commonalities among the metabolic profiles of overall and specific types of cancer: the top 20 frequently identified metabolites for 20 specific types of cancer were all associated with overall cancer; most of the specific types of cancer had common identified metabolites. Meanwhile, the associations between the same metabolite with different types of cancer can vary based on the site of origin. We identified 13 metabolic biomarkers associated with overall cancer, and found that they mediated the effects of traditional factors. The accuracies of prediction models improved when we added 13 identified metabolites in models. This study is helpful to understand the metabolic mechanisms of overall and a wide range of cancers, and our results also indicate that NMR metabolites are potential biomarkers in cancer diagnosis and prevention. Nuclear magnetic resonance (NMR) enables detailed quantification and qualitative study of associations between metabolites and cancer. Owing to high reproducibility in particular, NMR could greatly facilitate the identification of biomarkers for cancer detection and prognosis. In this study, using a cohort from the UK Biobank, the authors explored associations between NMR metabolites and risk of 20 common cancers. Each of the 20 most frequently identified metabolites were associated with overall cancer risk. Relationships between the same metabolite and different cancer types varied by tumor site. Mediation effects on traditional risk factors, including age and diet, were observed for 13 metabolites. image