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BMC Medicine
Published in: BMC Medicine 1/2017

Open Access 01-12-2017 | Research article

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: Julie A. Schmidt, Georgina K. Fensom, Sabina Rinaldi, Augustin Scalbert, Paul N. Appleby, David Achaintre, Audrey Gicquiau, Marc J. Gunter, Pietro Ferrari, Rudolf Kaaks, Tilman Kühn, Anna Floegel, Heiner Boeing, Antonia Trichopoulou, Pagona Lagiou, Eleutherios Anifantis, Claudia Agnoli, Domenico Palli, Morena Trevisan, Rosario Tumino, H. Bas Bueno-de-Mesquita, Antonio Agudo, Nerea Larrañaga, Daniel Redondo-Sánchez, Aurelio Barricarte, José Maria Huerta, J. Ramón Quirós, Nick Wareham, Kay-Tee Khaw, Aurora Perez-Cornago, Mattias Johansson, Amanda J. Cross, Konstantinos K. Tsilidis, Elio Riboli, Timothy J. Key, Ruth C. Travis

Published in: BMC Medicine | Issue 1/2017

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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.

Conclusions

Several metabolites, i.e. C18:1, citrulline, trans-4-hydroxyproline, three glycerophospholipids and SM (OH) C14:1, might be related to prostate cancer. Analyses by time to diagnosis indicated that citrulline may be a marker of subclinical prostate cancer, while other metabolites might be related to aetiology. Several glycerophospholipids were inversely related to advanced stage disease. More prospective data are needed to confirm these associations.
Appendix
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Metadata
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
Julie A. Schmidt
Georgina K. Fensom
Sabina Rinaldi
Augustin Scalbert
Paul N. Appleby
David Achaintre
Audrey Gicquiau
Marc J. Gunter
Pietro Ferrari
Rudolf Kaaks
Tilman Kühn
Anna Floegel
Heiner Boeing
Antonia Trichopoulou
Pagona Lagiou
Eleutherios Anifantis
Claudia Agnoli
Domenico Palli
Morena Trevisan
Rosario Tumino
H. Bas Bueno-de-Mesquita
Antonio Agudo
Nerea Larrañaga
Daniel Redondo-Sánchez
Aurelio Barricarte
José Maria Huerta
J. Ramón Quirós
Nick Wareham
Kay-Tee Khaw
Aurora Perez-Cornago
Mattias Johansson
Amanda J. Cross
Konstantinos K. Tsilidis
Elio Riboli
Timothy J. Key
Ruth C. Travis
Publication date
01-12-2017
Publisher
BioMed Central
Published in
BMC Medicine / Issue 1/2017
Electronic ISSN: 1741-7015
DOI
https://doi.org/10.1186/s12916-017-0885-6

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