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Research article - Peer-reviewed, 2022

Identification of prediagnostic 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

Ostman, Johnny R.; Pinto, Rui C.; Ebbels, Timothy M. D.; Thysell, Elin; Hallmans, Goran; Moazzami, Ali A.;

Abstract

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 prediagnostic 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 the following two decades.

Keywords

liquid chromatography-mass spectrometry; nested case-control study; prostate cancer; risk biomarkers; untargeted metabolomics

Published in

International Journal of Cancer

2022, volume: 151, number: 12, pages: 2115-2127
Publisher: WILEY

Authors' information

Swedish University of Agricultural Sciences, Department of Molecular Sciences
Pinto, Rui C.
Imperial College London
Ebbels, Timothy M. D.
Imperial College London
Thysell, Elin
Umea University
Hallmans, Goran
Umea University
Swedish University of Agricultural Sciences, Department of Molecular Sciences

Sustainable Development Goals

SDG3 Good health and wellbeing

UKÄ Subject classification

Cancer and Oncology

Publication Identifiers

DOI: https://doi.org/10.1002/ijc.34223

URI (permanent link to this page)

https://res.slu.se/id/publ/118748