Background and Objective: Nutrimetabolomics may reveal novel insights into early metabolic alterations and the role of dietary exposures on prostate cancer (PCa) risk. We aimed to prospectively investigate the associations between plasma metabolite concentrations and PCa risk, including clinically relevant tumor subtypes. Methods: We used a targeted and large-scale metabolomics approach to analyze plasma samples of 851 matched PCa case-control pairs from the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Associations between metabolite concentrations and PCa risk were estimated by multivariate conditional logistic regression analysis. False discovery rate (FDR) was used to control for multiple testing correction. Results: Thirty-one metabolites (predominately derivatives of food intake and microbial metabolism) were associated with overall PCa risk and its clinical subtypes (p < 0.05), but none of the associations exceeded the FDR threshold. The strongest positive and negative associations were for dimethylglycine (OR = 2.13; 95% CI 1.16-3.91) with advanced PCa risk (n = 157) and indole-3-lactic acid (OR = 0.28; 95% CI 0.09-0.87) with fatal PCa risk (n = 57), respectively; however, these associations did not survive correction for multiple testing. Conclusions: The results from the current nutrimetabolomics study suggest that apart from early metabolic deregulations, some biomarkers of food intake might be related to PCa risk, especially advanced and fatal PCa. Further independent and larger studies are needed to validate our results.
Cancers. 2024 Dec 08*** epublish ***
Enrique Almanza-Aguilera, Miriam Martínez-Huélamo, Yamilé López-Hernández, Daniel Guiñón-Fort, Anna Guadall, Meryl Cruz, Aurora Perez-Cornago, Agnetha L Rostgaard-Hansen, Anne Tjønneland, Christina C Dahm, Verena Katzke, Matthias B Schulze, Giovanna Masala, Claudia Agnoli, Rosario Tumino, Fulvio Ricceri, Cristina Lasheras, Marta Crous-Bou, Maria-Jose Sánchez, Amaia Aizpurua-Atxega, Marcela Guevara, Kostas K Tsilidis, Anastasia Chrysovalantou Chatziioannou, Elisabete Weiderpass, Ruth C Travis, David S Wishart, Cristina Andrés-Lacueva, Raul Zamora-Ros
Unit of Nutrition and Cancer, Cancer Epidemiology Research Program, Catalan Institute of Oncology (ICO), Bellvitge Biomedical Research Institute (IDIBELL), 08908 Barcelona, Spain., Centro de Investigación Biomédica en Red de Fragilidad y Envejecimiento Saludable (CIBERFES), Instituto de Salud Carlos III, 28029 Madrid, Spain., The Metabolomics Innovation Centre, University of Alberta, Edmonton, AB T6G 1C9, Canada., Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford OX3 7LF, UK., Danish Cancer Society Research Center, Diet, Cancer and Health, 2100 Copenhagen, Denmark., Department of Public Health, Aarhus University, 8000 Aarhus, Denmark., Department of Cancer Epidemiology, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany., Department of Molecular Epidemiology, German Institute of Human Nutrition Potsdam Rehbruecke, 14558 Nuthetal, Germany., Clinical Epidemiology Unit, Institute for Cancer Research, Prevention and Clinical Network (ISPRO), 50139 Florence, Italy., Department of Research Epidemiology and Prevention Unit, Fondazione IRCCS Istituto Nazionale Dei Tumori, 20133 Milan, Italy., Hyblean Association for Epidemiological Research, Associazione Iblea per la Ricerca Epidemiologica (AIRE-ONLUS), 97100 Ragusa, Italy., Centre for Biostatistics, Epidemiology, and Public Health (C-BEPH, Department of Clinical and Biological Sciences, University of Turin, Orbassano, 10043 Turin, Italy., Department of Functional Biology, Oviedo University, 33003 Oviedo, Spain., Escuela Andaluza de Salud Pública (EASP), 18011 Granada, Spain., Sub Directorate for Public Health and Addictions of Gipuzkoa, Ministry of Health of the Basque Government, 20013 San Sebastian, Spain., Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública (CIBERESP), 28029 Madrid, Spain., Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, St Mary's Campus, London SW7 2AZ, UK., International Agency for Research on Cancer (IARC/WHO), 69366 Lyon, France.