Identification of pre-diagnostic metabolites associated with prostate cancer risk by untargeted mass spectrometry-based metabolomics: A case-control study nested in the Northern Sweden Health and Disease Study.

Prostate cancer (PCa) is the most common cancer form in males in many European and American countries, but there are still open questions regarding its etiology. Untargeted metabolomics can produce an unbiased global metabolic profile, with the opportunity for uncovering new plasma metabolites prospectively associated with risk of PCa, providing insights into disease etiology. We conducted a prospective untargeted liquid chromatography-mass spectrometry (LC-MS) metabolomics analysis using pre-diagnostic fasting plasma samples from 752 PCa case-control pairs nested within the Northern Sweden Health and Disease Study (NSHDS). The pairs were matched by age, BMI, and sample storage time. Discriminating features were identified by a combination of orthogonal projection to latent structures-effect projections (OPLS-EP) and Wilcoxon signed-rank tests. Their prospective associations with PCa risk were investigated by conditional logistic regression. Subgroup analyses based on stratification by disease aggressiveness and baseline age were also conducted. Various free fatty acids and phospholipids were positively associated with overall risk of PCa and in various stratification subgroups. Aromatic amino acids were positively associated with overall risk of PCa. Uric acid was positively, and glucose negatively, associated with risk of PCa in the older subgroup. This is the largest untargeted LC-MS based metabolomics study to date on plasma metabolites prospectively associated with risk of developing PCa. Different subgroups of disease aggressiveness and baseline age showed different associations with metabolites. The findings suggest that shifts in plasma concentrations of metabolites in lipid, aromatic amino acid, and glucose metabolism are associated with risk of developing PCa during following two decades. This article is protected by copyright. All rights reserved.

International journal of cancer. 2022 Jul 22 [Epub ahead of print]

Johnny R Östman, Rui C Pinto, Timothy Md Ebbels, Elin Thysell, Göran Hallmans, Ali A Moazzami

Department of Molecular Sciences, Swedish University of Agricultural Sciences, Uppsala, Sweden., Department of Epidemiology and Biostatistics, MRC-PHE Centre for Environment and Health, School of Public Health, Imperial College London, St. Mary's Campus, Norfolk Place, W2 1PG, London, England, UK., Department of Metabolism, Digestion and Reproduction, Imperial College London, South Kensington, SW7 2AZ, London, England, UK., Department of Medical Biosciences, Umeå University, Umeå, Sweden., Department of Public Health and Clinical Medicine, Nutritional Research, Umeå University, Umeå, Sweden.

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