Pre-diagnostic metabolite concentrations and prostate cancer risk in 1077 cases and 1077 matched controls in the European Prospective Investigation into Cancer and Nutrition

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Title: Pre-diagnostic metabolite concentrations and prostate cancer risk in 1077 cases and 1077 matched controls in the European Prospective Investigation into Cancer and Nutrition
Authors: Schmidt, JA
Fensom, GK
Rinaldi, S
Scalbert, A
Appleby, PN
Achaintre, D
Gicquiau, A
Gunter, MJ
Ferrari, P
Kaaks, R
Kuhn, T
Floegel, A
Boeing, H
Trichopoulou, A
Lagiou, P
Anifantis, E
Agnoli, C
Palli, C
Trevisan, M
Tumino, R
Bueno-de-Mesquita, B
Agudo, A
Larranaga, N
Redondo-Sanchez, D
Barricarte, A
Huerta, JM
Ramon Quiros, J
Wareham, N
Khaw, KT
Perez-Cornago, A
Johansson, M
Cross, A
Tsilidis, K
Riboli, E
Key, TJ
Travis, RC
Item Type: Journal Article
Abstract: Background Little is known about how pre-diagnostic metabolites in blood relate to risk of prostate cancer. We aimed to investigate the prospective association between plasma metabolite concentrations and risk of prostate cancer overall, and by time to diagnosis and tumour characteristics, and risk of death from prostate cancer. Methods In a case-control study nested in the European Prospective Investigation into Cancer and Nutrition, pre-diagnostic plasma concentrations of 122 metabolites (including acylcarnitines, amino acids, biogenic amines, glycerophospholipids, hexose and sphingolipids) were measured using targeted mass spectrometry (AbsoluteIDQ p180 Kit) and compared between 1077 prostate cancer cases and 1077 matched controls. Risk of prostate cancer associated with metabolite concentrations was estimated by multi-variable conditional logistic regression, and multiple testing was accounted for by using a false discovery rate controlling procedure. Results Seven metabolite concentrations, i.e. acylcarnitine C18:1, amino acids citrulline and trans-4-hydroxyproline, glycerophospholipids PC aa C28:1, PC ae C30:0 and PC ae C30:2, and sphingolipid SM (OH) C14:1, were associated with prostate cancer (p < 0.05), but none of the associations were statistically significant after controlling for multiple testing. Citrulline was associated with a decreased risk of prostate cancer (odds ratio (OR1SD) = 0.73; 95% confidence interval (CI) 0.62–0.86; p trend = 0.0002) in the first 5 years of follow-up after taking multiple testing into account, but not after longer follow-up; results for other metabolites did not vary by time to diagnosis. After controlling for multiple testing, 12 glycerophospholipids were inversely associated with advanced stage disease, with risk reduction up to 46% per standard deviation increase in concentration (OR1SD = 0.54; 95% CI 0.40–0.72; p trend = 0.00004 for PC aa C40:3). Death from prostate cancer was associated with higher concentrations of acylcarnitine C3, amino acids methionine and trans-4-hydroxyproline, biogenic amine ADMA, hexose and sphingolipid SM (OH) C14:1 and lower concentration of glycerophospholipid PC aa C42:4.
Issue Date: 5-Jul-2017
Date of Acceptance: 26-May-2017
ISSN: 1741-7015
Publisher: BioMed Central
Journal / Book Title: BMC Medicine
Volume: 15
Copyright Statement: © The Author(s). 2017. Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (, which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( applies to the data made available in this article, unless otherwise stated.
Sponsor/Funder: Imperial College Trust
Funder's Grant Number: P47328
Keywords: Science & Technology
Life Sciences & Biomedicine
Medicine, General & Internal
General & Internal Medicine
Amino acids
Biogenic amines
European Prospective Investigation into Cancer and Nutrition (EPIC)
Mass spectrometry
Prospective study
Prostate cancer risk
11 Medical And Health Sciences
Publication Status: Published
Article Number: 122
Appears in Collections:Faculty of Medicine
Epidemiology, Public Health and Primary Care

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