BMC Medicine (Oct 2022)
Pan-cancer analysis of pre-diagnostic blood metabolite concentrations in the European Prospective Investigation into Cancer and Nutrition
- Marie Breeur,
- Pietro Ferrari,
- Laure Dossus,
- Mazda Jenab,
- Mattias Johansson,
- Sabina Rinaldi,
- Ruth C. Travis,
- Mathilde His,
- Tim J. Key,
- Julie A. Schmidt,
- Kim Overvad,
- Anne Tjønneland,
- Cecilie Kyrø,
- Joseph A. Rothwell,
- Nasser Laouali,
- Gianluca Severi,
- Rudolf Kaaks,
- Verena Katzke,
- Matthias B. Schulze,
- Fabian Eichelmann,
- Domenico Palli,
- Sara Grioni,
- Salvatore Panico,
- Rosario Tumino,
- Carlotta Sacerdote,
- Bas Bueno-de-Mesquita,
- Karina Standahl Olsen,
- Torkjel Manning Sandanger,
- Therese Haugdahl Nøst,
- J. Ramón Quirós,
- Catalina Bonet,
- Miguel Rodríguez Barranco,
- María-Dolores Chirlaque,
- Eva Ardanaz,
- Malte Sandsveden,
- Jonas Manjer,
- Linda Vidman,
- Matilda Rentoft,
- David Muller,
- Kostas Tsilidis,
- Alicia K. Heath,
- Hector Keun,
- Jerzy Adamski,
- Pekka Keski-Rahkonen,
- Augustin Scalbert,
- Marc J. Gunter,
- Vivian Viallon
Affiliations
- Marie Breeur
- Nutrition and Metabolism Branch, International Agency for Research on Cancer, NME Branch
- Pietro Ferrari
- Nutrition and Metabolism Branch, International Agency for Research on Cancer, NME Branch
- Laure Dossus
- Nutrition and Metabolism Branch, International Agency for Research on Cancer, NME Branch
- Mazda Jenab
- Nutrition and Metabolism Branch, International Agency for Research on Cancer, NME Branch
- Mattias Johansson
- Genetics Branch, International Agency for Research on Cancer
- Sabina Rinaldi
- Nutrition and Metabolism Branch, International Agency for Research on Cancer, NME Branch
- Ruth C. Travis
- Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford
- Mathilde His
- Nutrition and Metabolism Branch, International Agency for Research on Cancer, NME Branch
- Tim J. Key
- Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford
- Julie A. Schmidt
- Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford
- Kim Overvad
- Department of Public Health, Aarhus University
- Anne Tjønneland
- Danish Cancer Society Research Center Diet, Genes and Environment Nutrition and Biomarkers
- Cecilie Kyrø
- Danish Cancer Society Research Center Diet, Genes and Environment Nutrition and Biomarkers
- Joseph A. Rothwell
- Université Paris-Saclay, UVSQ, Inserm, CESP U1018, “Exposome and Heredity” team, Gustave Roussy
- Nasser Laouali
- Université Paris-Saclay, UVSQ, Inserm, CESP U1018, “Exposome and Heredity” team, Gustave Roussy
- Gianluca Severi
- Université Paris-Saclay, UVSQ, Inserm, CESP U1018, “Exposome and Heredity” team, Gustave Roussy
- Rudolf Kaaks
- Division of Cancer Epidemiology, German Cancer Research Center (DKFZ)
- Verena Katzke
- Division of Cancer Epidemiology, German Cancer Research Center (DKFZ)
- Matthias B. Schulze
- Department of Molecular Epidemiology, German Institute of Human Nutrition
- Fabian Eichelmann
- Department of Molecular Epidemiology, German Institute of Human Nutrition
- Domenico Palli
- Institute of Cancer Research, Prevention and Clinical Network (ISPRO)
- Sara Grioni
- Epidemiology and Prevention Unit, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano
- Salvatore Panico
- Dipartimento di Medicina Clinica e Chirurgia, Federico II University
- Rosario Tumino
- Hyblean Association for Epidemiological Research, AIRE-ONLUS
- Carlotta Sacerdote
- Unit of Cancer Epidemiology Città della Salute e della Scienza University-Hospital
- Bas Bueno-de-Mesquita
- Centre for Nutrition, Prevention and Health Services, National Institute for Public Health and the Environment (RIVM)
- Karina Standahl Olsen
- Department of Community Medicine, UiT The Arctic University of Norway
- Torkjel Manning Sandanger
- Department of Community Medicine, UiT The Arctic University of Norway
- Therese Haugdahl Nøst
- Department of Community Medicine, UiT The Arctic University of Norway
- J. Ramón Quirós
- Public Health Directorate
- Catalina Bonet
- Unit of Nutrition and Cancer, Cancer Epidemiology Research Program, Catalan Institute of Oncology (ICO), Bellvitge Biomedical Research Institute (IDIBELL), L’Hospitalet de Llobregat
- Miguel Rodríguez Barranco
- Escuela Andaluza de Salud Pública (EASP)
- María-Dolores Chirlaque
- Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública (CIBERESP)
- Eva Ardanaz
- Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública (CIBERESP)
- Malte Sandsveden
- Department of Clinical Sciences Malmö Lund University
- Jonas Manjer
- Departement of Surgery, Skåne University Hospital Malmö, Lund University
- Linda Vidman
- Department of Radiation Sciences, Oncology Umeå University
- Matilda Rentoft
- Department of Radiation Sciences, Oncology Umeå University
- David Muller
- Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London
- Kostas Tsilidis
- Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London
- Alicia K. Heath
- Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London
- Hector Keun
- Department of Surgery and Cancer, Cancer Metabolism and Systems Toxicology Group, Division of Cancer, Imperial College London
- Jerzy Adamski
- Institute of Experimental Genetics, Helmholtz Zentrum München, German Research Center for Environmental Health
- Pekka Keski-Rahkonen
- Nutrition and Metabolism Branch, International Agency for Research on Cancer, NME Branch
- Augustin Scalbert
- Nutrition and Metabolism Branch, International Agency for Research on Cancer, NME Branch
- Marc J. Gunter
- Nutrition and Metabolism Branch, International Agency for Research on Cancer, NME Branch
- Vivian Viallon
- Nutrition and Metabolism Branch, International Agency for Research on Cancer, NME Branch
- DOI
- https://doi.org/10.1186/s12916-022-02553-4
- Journal volume & issue
-
Vol. 20,
no. 1
pp. 1 – 17
Abstract
Abstract Background Epidemiological studies of associations between metabolites and cancer risk have typically focused on specific cancer types separately. Here, we designed a multivariate pan-cancer analysis to identify metabolites potentially associated with multiple cancer types, while also allowing the investigation of cancer type-specific associations. Methods We analysed targeted metabolomics data available for 5828 matched case-control pairs from cancer-specific case-control studies on breast, colorectal, endometrial, gallbladder, kidney, localized and advanced prostate cancer, and hepatocellular carcinoma nested within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. From pre-diagnostic blood levels of an initial set of 117 metabolites, 33 cluster representatives of strongly correlated metabolites and 17 single metabolites were derived by hierarchical clustering. The mutually adjusted associations of the resulting 50 metabolites with cancer risk were examined in penalized conditional logistic regression models adjusted for body mass index, using the data-shared lasso penalty. Results Out of the 50 studied metabolites, (i) six were inversely associated with the risk of most cancer types: glutamine, butyrylcarnitine, lysophosphatidylcholine a C18:2, and three clusters of phosphatidylcholines (PCs); (ii) three were positively associated with most cancer types: proline, decanoylcarnitine, and one cluster of PCs; and (iii) 10 were specifically associated with particular cancer types, including histidine that was inversely associated with colorectal cancer risk and one cluster of sphingomyelins that was inversely associated with risk of hepatocellular carcinoma and positively with endometrial cancer risk. Conclusions These results could provide novel insights for the identification of pathways for cancer development, in particular those shared across different cancer types.
Keywords
