Prospective analysis of circulating metabolites and breast cancer in EPIC

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  • Mathilde His, International Agency for Research on Cancer, 150 Cours Albert-Thomas, 69372 Lyon Cedex 08, France., Frankrig
  • Vivian Viallon, International Agency for Research on Cancer, 150 Cours Albert-Thomas, 69372 Lyon Cedex 08, France., Frankrig
  • Laure Dossus, International Agency for Research on Cancer, 150 Cours Albert-Thomas, 69372 Lyon Cedex 08, France., Frankrig
  • Audrey Gicquiau, International Agency for Research on Cancer, 150 Cours Albert-Thomas, 69372 Lyon Cedex 08, France., Frankrig
  • David Achaintre, International Agency for Research on Cancer, 150 Cours Albert-Thomas, 69372 Lyon Cedex 08, France., Frankrig
  • Augustin Scalbert, International Agency for Research on Cancer, 150 Cours Albert-Thomas, 69372 Lyon Cedex 08, France., Frankrig
  • Pietro Ferrari, International Agency for Research on Cancer, 150 Cours Albert-Thomas, 69372 Lyon Cedex 08, France., Frankrig
  • Isabelle Romieu, Centre for Research on Population Health, National Institute of Public Health, Cuernavaca, Mexico., Mexico
  • N Charlotte Onland-Moret, Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands., Holland
  • Elisabete Weiderpass, International Agency for Research on Cancer, 150 Cours Albert-Thomas, 69372 Lyon Cedex 08, France., Frankrig
  • Christina C Dahm
  • Kim Overvad
  • Anja Olsen
  • Anne Tjønneland, Department of Cardiology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark Danish Arrhythmia Research Centre, University of Copenhagen, Copenhagen, Denmark., Danmark
  • Agnès Fournier, Institut Gustave Roussy, Villejuif, France., Frankrig
  • Joseph A Rothwell, Institut Gustave Roussy, Villejuif, France., Frankrig
  • Gianluca Severi, Institut Gustave Roussy, Villejuif, France., Frankrig
  • Tilman Kühn, Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany. r.kaaks@dkfz-heidelberg.de., Tyskland
  • Renée T Fortner, Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany. r.kaaks@dkfz-heidelberg.de., Tyskland
  • Heiner Boeing, Department of Epidemiology, German Institute of Human Nutrition Potsdam-Rehbruecke (DIfE), Arthur-Scheunert-Allee 114-116, 14558, Nuthetal, Germany., Tyskland
  • Antonia Trichopoulou, Hellenic Health Foundation, Athens, Greece., Grækenland
  • Anna Karakatsani, 2nd Pulmonary Medicine Department, School of Medicine, National and Kapodistrian University of Athens, "ATTIKON" University Hospital, Haidari, Greece., Grækenland
  • Georgia Martimianaki, Hellenic Health Foundation, Athens, Greece., Grækenland
  • Giovanna Masala, Cancer Risk Factors and Life-Style Epidemiology Unit. Institute for Cancer Research, Prevention and Clinical Network - ISPRO, 50141, Florence, Italy., Italien
  • Sabina Sieri, Epidemiology and Prevention Unit, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, Milan, Italy., Italien
  • Rosario Tumino, Cancer Registry and Histopathology Department, Civic-M.P.Arezzo Hospital, ASP, 97100 Ragusa, Italy. rtumino@tin.it., Italien
  • Paolo Vineis, Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK; MRC-PHE Centre for Environment, School of Public Health, Imperial College London, London, UK; Department of Hygiene and Epidemiology, University of Ioannina Medical School, Ioannina, Greece., Storbritannien
  • Salvatore Panico, Dipartimento die Medicina Clinica e Chirurgia, Federico II University, Naples, Italy., Italien
  • Carla H van Gils, Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands., Holland
  • Therese H Nøst, Department of Community Medicine, UiT The Arctic University of Norway, Tromso, Norway., Norge
  • Torkjel M Sandanger, Department of Community Medicine, UiT The Arctic University of Norway, Tromso, Norway., Norge
  • Guri Skeie, Nutritional Epidemiology Group, School of Food Science and Nutrition, University of Leeds, Leeds, UK., Storbritannien
  • J Ramón Quirós, Public Health Directorate, Asturias, Spain., Spanien
  • Antonio Agudo, Unit of Nutrition and Cancer. Cancer Epidemiology Research Program, Catalan Institute of Oncology-IDIBELL. L'Hospitalet de Llobregat, Barcelona, Spain., Spanien
  • Maria-Jose Sánchez, Department of Epidemiology, Regional Health Council, IMIB-Arrixaca, Murcia University, Spain; CIBER in Epidemiology and Public Health (CIBERESP), Madrid, Spain., Spanien
  • Pilar Amiano, Public Health Division of Gipuzkoa, Basque Government, Spain; Health Research Institute, Biodonostia, San Sebastián, Spain., Spanien
  • José María Huerta, Department of Epidemiology, Regional Health Council, IMIB-Arrixaca, Murcia, Spain., Spanien
  • Eva Ardanaz, Navarre Public Health Institute, Pamplona, Navarra Institute for Health Research (IdiSNA), Pamplona, Spain., Spanien
  • Julie A Schmidt, Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, UK., Storbritannien
  • Ruth C Travis, Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, UK., Storbritannien
  • Elio Riboli, Department of Epidemiology and Biostatistics, , The School of Public Health, Imperial College London, St Mary's Campus, Norfolk Place, London, W2 1PG London, United Kingdom., Storbritannien
  • Konstantinos K Tsilidis, Department of Hygiene and Epidemiology, University of Ioannina School of Medicine, 45110 Ioannina, Greece. ktsilidis@gmail.com., Grækenland
  • Sofia Christakoudi, MRC Centre for Transplantation, King's College London, Great Maze Pond, London SE1 9RT, United Kingdom., Storbritannien
  • Marc J Gunter, International Agency for Research on Cancer, 150 Cours Albert-Thomas, 69372 Lyon Cedex 08, France., Frankrig
  • Sabina Rinaldi, International Agency for Research on Cancer, 150 cours Albert Thomas, 69372, Lyon CEDEX 08, France. rinaldis@iarc.fr., Frankrig

BACKGROUND: Metabolomics is a promising molecular tool to identify novel etiologic pathways leading to cancer. Using a targeted approach, we prospectively investigated the associations between metabolite concentrations in plasma and breast cancer risk.

METHODS: A nested case-control study was established within the European Prospective Investigation into Cancer cohort, which included 1624 first primary incident invasive breast cancer cases (with known estrogen and progesterone receptor and HER2 status) and 1624 matched controls. Metabolites (n = 127, acylcarnitines, amino acids, biogenic amines, glycerophospholipids, hexose, sphingolipids) were measured by mass spectrometry in pre-diagnostic plasma samples and tested for associations with breast cancer incidence using multivariable conditional logistic regression.

RESULTS: Among women not using hormones at baseline (n = 2248), and after control for multiple tests, concentrations of arginine (odds ratio [OR] per SD = 0.79, 95% confidence interval [CI] = 0.70-0.90), asparagine (OR = 0.83 (0.74-0.92)), and phosphatidylcholines (PCs) ae C36:3 (OR = 0.83 (0.76-0.90)), aa C36:3 (OR = 0.84 (0.77-0.93)), ae C34:2 (OR = 0.85 (0.78-0.94)), ae C36:2 (OR = 0.85 (0.78-0.88)), and ae C38:2 (OR = 0.84 (0.76-0.93)) were inversely associated with breast cancer risk, while the acylcarnitine C2 (OR = 1.23 (1.11-1.35)) was positively associated with disease risk. In the overall population, C2 (OR = 1.15 (1.06-1.24)) and PC ae C36:3 (OR = 0.88 (0.82-0.95)) were associated with risk of breast cancer, and these relationships did not differ by breast cancer subtype, age at diagnosis, fasting status, menopausal status, or adiposity.

CONCLUSIONS: These findings point to potentially novel pathways and biomarkers of breast cancer development. Results warrant replication in other epidemiological studies.

OriginalsprogEngelsk
Artikelnummer178
TidsskriftBMC Medicine
Vol/bind17
Nummer1
Antal sider13
ISSN1741-7015
DOI
StatusUdgivet - 24 sep. 2019

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