Perturbations in the blood metabolome up to a decade before prostate cancer diagnosis in 4387 matched case–control sets from the European Prospective Investigation into Cancer and Nutrition
Measuring pre-diagnostic blood metabolites may help identify novel risk factors for prostate cancer. Using data from 4387 matched case-control pairs from the European Prospective Investigation into Cancer and Nutrition (EPIC) study, we investigated the associations of 148 individual metabolites and three previously defined metabolite patterns with prostate cancer risk. Metabolites were measured by liquid chromatography-mass spectrometry. Multivariable-adjusted conditional logistic regression was used to estimate the odds ratio per standard deviation increase in log metabolite concentration and metabolite patterns (OR1SD) for prostate cancer overall, and for advanced, high-grade, aggressive. We corrected for multiple testing using the Benjamini-Hochberg method. Overall, there were no associations between specific metabolites or metabolite patterns and overall, aggressive, or high-grade prostate cancer that passed the multiple testing threshold (padj <0.05). Six phosphatidylcholines (PCs) were inversely associated with advanced prostate cancer diagnosed at or within 10 years of blood collection. metabolite patterns 1 (64 PCs and three hydroxysphingomyelins) and 2 (two acylcarnitines, glutamate, ornithine, and taurine) were also inversely associated with advanced prostate cancer; when stratified by follow-up time, these associations were observed for diagnoses at or within 10 years of recruitment (OR<sub>1SD</sub> 0.80, 95% CI 0.66-0.96 and 0.76, 0.59-0.97, respectively) but were weaker after longer follow-up (0.95, 0.82-1.10 and 0.85, 0.67-1.06). Pattern 3 (8 lyso PCs) was associated with prostate cancer death (0.82, 0.68-0.98). Our results suggest that the plasma metabolite profile changes in response to the presence of prostate cancer up to a decade before detection of advanced-stage disease.
Authors
- Urwah Noor (ORCID: https://orcid.org/0009-0007-3885-5898)
- Sofia Christakoudi (ORCID: https://orcid.org/0000-0001-9219-4436)
- Alberto Catalano (ORCID: https://orcid.org/0000-0003-2597-2060)
- Sabina Rinaldi (ORCID: https://orcid.org/0000-0002-6846-1204)
- Claudia Agnoli (ORCID: https://orcid.org/0000-0003-4472-1179)
- Zoe S. Grenville (ORCID: https://orcid.org/0000-0002-8185-5929)
- Ruth C. Travis (ORCID: https://orcid.org/0000-0002-9571-0763)
- Matthias Bernd Schulze (ORCID: https://orcid.org/0000-0002-0830-5277)
- Julie A. Schmidt (ORCID: https://orcid.org/0000-0002-7733-8750)
- Rosario Tumino (ORCID: https://orcid.org/0000-0003-2666-414X)
- Giovanna Masala (ORCID: https://orcid.org/0000-0002-5758-9069)
- Timothy J. Key (ORCID: https://orcid.org/0000-0003-2294-307X)
- Marcela Guevara (ORCID: https://orcid.org/0000-0001-9242-6364)
- Karl Smith‐Byrne
- Marc J. Gunter (ORCID: https://orcid.org/0000-0001-5472-6761)
- Raúl Zamora‐Ros (ORCID: https://orcid.org/0000-0002-6236-6804)
- Pilar Amiano (ORCID: https://orcid.org/0000-0003-3986-7026)
- Elisabete Weiderpass (ORCID: https://orcid.org/0000-0003-2237-0128)
- Pietro Ferrari (ORCID: https://orcid.org/0000-0002-2512-6561)
- Anne Marie Tjønneland (ORCID: https://orcid.org/0000-0003-4385-2097)
- Keren Papier (ORCID: https://orcid.org/0000-0002-4102-6835)
- María‐José Sánchez (ORCID: https://orcid.org/0000-0003-4817-0757)
- Tammy Y. N. Tong (ORCID: https://orcid.org/0000-0002-0284-8959)
- Rudolf Kaaks
- Verena Katzke
- Matthias Johansson
- Anja Olsen
- María Dolores Chirlaque
Institutions
- Università degli Studi del Piemonte Orientale “Amedeo Avogadro” (IT)
- University of Copenhagen (DK)
- Universidad de Granada (ES)
- University of Potsdam (DE)
- German Cancer Research Center (DE)
- Aarhus University (DK)
- Heidelberg University (DE)
- Basque Government (ES)
- Aarhus University Hospital (DK)
- University of Oxford (GB)
- Instituto de Salud Pública de Navarra (ES)
- Institut d'Investigació Biomédica de Bellvitge (ES)
- Ministry of Health (ES)
- Biogipuzkoa Health Research Institute (ES)
- Institut Català d'Oncologia (ES)
- Navarre Institute of Health Research (ES)
- Instituto de Investigación Biosanitaria de Granada (ES)
- Italian Association for Cancer Research (IT)
- Instituto Murciano de Investigación Biosanitaria (ES)
- Danish Cancer Society (DK)
- Piedmont Reference Center for Epidemiology and Cancer Prevention (IT)
- Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública (ES)
- Fondazione IRCCS Istituto Nazionale dei Tumori (IT)
- German Institute of Human Nutrition (DE)
- Centre international de recherche sur le cancer (FR)
- Imperial College London (GB)
- University of Turin (IT)
- Andalusian School of Public Health (ES)
Publication Details
- Journal
- International Journal of Cancer
- Published
- 2024-10-08
- DOI
- https://doi.org/10.1002/ijc.35208
- Citations
- 4
- Primary Topic
- Metabolomics and Mass Spectrometry Studies
- Type
- article
- Field-Weighted Citation Impact
- 0.94
Funders
- World Health Organization
- Centres de Recerca de Catalunya
- Cancer Research UK
- Universiteit Utrecht
- Generalitat de Catalunya
- Instituto de Salud Carlos III
- Rijksinstituut voor Volksgezondheid en Milieu
- European Social Fund