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. Issue 12 (12th August 2022)

• Record Type: Journal Article
• Authors: Östman, Johnny R.; Pinto, Rui C.; Ebbels, Timothy M. D.; Thysell, Elin; Hallmans, Göran; Moazzami, Ali A.
• Is Part Of: International journal of cancer. Volume 151:Issue 12(2022)
• Page Start: 2115
• Page End: 2127
• Publication Date: 2022-08-12
• Subjects: liquid chromatography‐mass spectrometry -- nested case‐control study -- prostate cancer -- risk biomarkers -- untargeted metabolomics; Cancer -- Periodicals; Cancer -- Prevention -- Periodicals; 616.994
• DOI: 10.1002/ijc.34223
• Languages: English
• ISSNs: 0020-7136

Abstract

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. Abstract : What's new? The identification of novel metabolic risk factors is a critical step in the advance of prevention strategies for prostate cancer. In the present study, using untargeted liquid chromatography‐mass spectrometry metabolomics, the authors examined prospective associations between circulating metabolites and prostate cancer risk. The analyses uncover positive associations between prostate cancer risk and aromatic amino acids, free fatty acids, uric acid, and phospholipids. Meanwhile, glucose was negatively associated with risk among older participants. The findings cast light on potentially clinically relevant associations between prostate cancer risk and plasma concentrations of metabolites generated by aromatic amino acid, lipid, and glucose metabolism.