EBioMedicine (Mar 2024)
Association between pre-diagnostic circulating lipid metabolites and colorectal cancer risk: a nested case–control study in the European Prospective Investigation into Cancer and Nutrition (EPIC)Research in context
- Rhea Harewood,
- Joseph A. Rothwell,
- Jelena Bešević,
- Vivian Viallon,
- David Achaintre,
- Audrey Gicquiau,
- Sabina Rinaldi,
- Roland Wedekind,
- Cornelia Prehn,
- Jerzy Adamski,
- Julie A. Schmidt,
- Inarie Jacobs,
- Anne Tjønneland,
- Anja Olsen,
- Gianluca Severi,
- Rudolf Kaaks,
- Verena Katzke,
- Matthias B. Schulze,
- Marcela Prada,
- Giovanna Masala,
- Claudia Agnoli,
- Salvatore Panico,
- Carlotta Sacerdote,
- Paula Gabriela Jakszyn,
- Maria-Jose Sánchez,
- Jesús Castilla,
- María-Dolores Chirlaque,
- Amaia Aizpurua Atxega,
- Bethany van Guelpen,
- Alicia K. Heath,
- Keren Papier,
- Tammy Y.N. Tong,
- Scott A. Summers,
- Mary Playdon,
- Amanda J. Cross,
- Pekka Keski-Rahkonen,
- Véronique Chajès,
- Neil Murphy,
- Marc J. Gunter
Affiliations
- Rhea Harewood
- International Agency for Research on Cancer (IARC), 25 Av. Tony Garnier, 69007, Lyon, France; Corresponding author. International Agency for Research on Cancer, World Health Organisation, 25 Avenue Tony Garnier, 69007, Lyon, France.
- Joseph A. Rothwell
- Centre for Epidemiology and Population Health (U1018), Exposome and Heredity Team, Faculté de Médecine, Université Paris-Saclay, UVSQ, INSERM, Gustave Roussy, F-94805, Villejuif, France
- Jelena Bešević
- Clinical Trial Service Unit, Nuffield Department of Population Health, University of Oxford, Oxford, UK
- Vivian Viallon
- International Agency for Research on Cancer (IARC), 25 Av. Tony Garnier, 69007, Lyon, France
- David Achaintre
- International Agency for Research on Cancer (IARC), 25 Av. Tony Garnier, 69007, Lyon, France; School of Plant Sciences and Food Security, Faculty of Biology, Tel-Aviv University, Tel Aviv-Yafo, Israel
- Audrey Gicquiau
- International Agency for Research on Cancer (IARC), 25 Av. Tony Garnier, 69007, Lyon, France
- Sabina Rinaldi
- International Agency for Research on Cancer (IARC), 25 Av. Tony Garnier, 69007, Lyon, France
- Roland Wedekind
- International Agency for Research on Cancer (IARC), 25 Av. Tony Garnier, 69007, Lyon, France
- Cornelia Prehn
- Metabolomics and Proteomics Core, Helmholtz Zentrum München, 85764, Neuherberg, Germany
- Jerzy Adamski
- Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, 8 Medical Drive, Singapore, 117597; Institute of Experimental Genetics, Helmholtz Zentrum München, German Research Center for Environmental Health, Ingolstädter Landstraße 1, 85764, Neuherberg, Germany; Institute of Biochemistry, Faculty of Medicine, University of Ljubljana, Vrazov trg 2, 1000, Ljubljana, Slovenia
- Julie A. Schmidt
- Department of Clinical Medicine, Department of Clinical Epidemiology, Aarhus University and Aarhus University Hospital, Olof Palmes Allé 43-45, 8200 Aarhus N, Denmark
- Inarie Jacobs
- International Agency for Research on Cancer (IARC), 25 Av. Tony Garnier, 69007, Lyon, France
- Anne Tjønneland
- Danish Cancer Society Research Center, Diet, Cancer and Health, Strandboulevarden 49, DK-2100, Copenhagen, Denmark; Department of Public Health, University of Copenhagen, Copenhagen, Denmark
- Anja Olsen
- Danish Cancer Society Research Center, Diet, Cancer and Health, Strandboulevarden 49, DK-2100, Copenhagen, Denmark; The Department of Public Health, University of Aarhus, Aarhus, Denmark
- Gianluca Severi
- Centre for Epidemiology and Population Health (U1018), Exposome and Heredity Team, Faculté de Médecine, Université Paris-Saclay, UVSQ, INSERM, Gustave Roussy, F-94805, Villejuif, France; Department of Statistics, Computer Science, Applications “G. Parenti”, University of Florence, Florence, Italy
- Rudolf Kaaks
- German Cancer Research Center (DKFZ), Division of Cancer Epidemiology, Heidelberg, Germany
- Verena Katzke
- German Cancer Research Center (DKFZ), Division of Cancer Epidemiology, Heidelberg, Germany
- Matthias B. Schulze
- Department of Molecular Epidemiology, German Institute of Human Nutrition Potsdam-Rehbruecke, Arthur-Scheunert-Allee 114-116, 14558, Nuthetal, Germany; Institute of Nutritional Science, University of Potsdam, Nuthetal, Germany
- Marcela Prada
- Department of Molecular Epidemiology, German Institute of Human Nutrition Potsdam-Rehbruecke, Arthur-Scheunert-Allee 114-116, 14558, Nuthetal, Germany
- Giovanna Masala
- Institute for Cancer Research, Prevention and Clinical Network (ISPRO), Florence, Italy
- Claudia Agnoli
- Epidemiology and Prevention Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Via Venezian, 1, 20133, Milan, Italy
- Salvatore Panico
- Dipartimento Di Medicina Clinica E Chirurgia Federico Ii University, Naples, Italy
- Carlotta Sacerdote
- Unit of Cancer Epidemiology, Città della Salute e della Scienza University-Hospital and Center for Cancer Prevention (CPO), Via Santena 7, 10126, Turin, Italy
- Paula Gabriela Jakszyn
- Unit of Nutrition and Cancer, Cancer Epidemiology Research Programme, Catalan Institute of Oncology (ICO-IDIBELL), Barcelona, Spain; Blanquerna School of Health Sciences, Ramon Llull University, Barcelona, Spain
- Maria-Jose Sánchez
- Escuela Andaluza de Salud Pública (EASP), 18011, Granada, Spain; Instituto de Investigación Biosanitaria ibs.GRANADA, 18012, Granada, Spain; Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública (CIBERESP), 28029, Madrid, Spain; Department of Preventive Medicine and Public Health, University of Granada, 18071, Granada, Spain
- Jesús Castilla
- Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública (CIBERESP), 28029, Madrid, Spain; Instituto de Salud Pública de Navarra – IdiSNA, Pamplona, Spain
- María-Dolores Chirlaque
- Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública (CIBERESP), 28029, Madrid, Spain; Department of Epidemiology, Regional Health Council, IMIB-Arrixaca, Murcia University, Murcia, Spain
- Amaia Aizpurua Atxega
- Ministry of Health of the Basque Government, Sub Directorate for Public Health and Addictions of Gipuzkoa, San Sebastian, Spain; Biodonostia Health Research Institute, Epidemiology of Chronic and Communicable Diseases Group, San Sebastián, Spain
- Bethany van Guelpen
- Department of Radiation Sciences, Oncology, Umeå University, Umeå, Sweden; Wallenberg Centre for Molecular Medicine, Umeå University, Umeå, Sweden
- Alicia K. Heath
- Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK
- Keren Papier
- Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, UK
- Tammy Y.N. Tong
- Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, UK
- Scott A. Summers
- Department of Nutrition and Integrative Physiology and the Diabetes and Metabolism Research Center, University of Utah, Salt Lake City, Utah, USA
- Mary Playdon
- Department of Nutrition and Integrative Physiology and the Diabetes and Metabolism Research Center, University of Utah, Salt Lake City, Utah, USA; Cancer Control and Population Sciences, Huntsman Cancer Institute, Salt Lake City, Utah, USA
- Amanda J. Cross
- Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK
- Pekka Keski-Rahkonen
- International Agency for Research on Cancer (IARC), 25 Av. Tony Garnier, 69007, Lyon, France
- Véronique Chajès
- International Agency for Research on Cancer (IARC), 25 Av. Tony Garnier, 69007, Lyon, France
- Neil Murphy
- International Agency for Research on Cancer (IARC), 25 Av. Tony Garnier, 69007, Lyon, France
- Marc J. Gunter
- International Agency for Research on Cancer (IARC), 25 Av. Tony Garnier, 69007, Lyon, France; Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK
- Journal volume & issue
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Vol. 101
p. 105024
Abstract
Summary: Background: Altered lipid metabolism is a hallmark of cancer development. However, the role of specific lipid metabolites in colorectal cancer development is uncertain. Methods: In a case–control study nested within the European Prospective Investigation into Cancer and Nutrition (EPIC), we examined associations between pre-diagnostic circulating concentrations of 97 lipid metabolites (acylcarnitines, glycerophospholipids and sphingolipids) and colorectal cancer risk. Circulating lipids were measured using targeted mass spectrometry in 1591 incident colorectal cancer cases (55% women) and 1591 matched controls. Multivariable conditional logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for associations between concentrations of individual lipid metabolites and metabolite patterns with colorectal cancer risk. Findings: Of the 97 assayed lipids, 24 were inversely associated (nominally p < 0.05) with colorectal cancer risk. Hydroxysphingomyelin (SM (OH)) C22:2 (ORper doubling 0.60, 95% CI 0.47–0.77) and acylakyl-phosphatidylcholine (PC ae) C34:3 (ORper doubling 0.71, 95% CI 0.59–0.87) remained associated after multiple comparisons correction. These associations were unaltered after excluding the first 5 years of follow-up after blood collection and were consistent according to sex, age at diagnosis, BMI, and colorectal subsite. Two lipid patterns, one including 26 phosphatidylcholines and all sphingolipids, and another 30 phosphatidylcholines, were weakly inversely associated with colorectal cancer. Interpretation: Elevated pre-diagnostic circulating levels of SM (OH) C22:2 and PC ae C34:3 and lipid patterns including phosphatidylcholines and sphingolipids were associated with lower colorectal cancer risk. This study may provide insight into potential links between specific lipids and colorectal cancer development. Additional prospective studies are needed to validate the observed associations. Funding: World Cancer Research Fund (reference: 2013/1002); European Commission (FP7: BBMRI-LPC; reference: 313010).
