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Prospective analysis of circulating metabolites and endometrial cancer risk.
Dossus, Laure; Kouloura, Eirini; Biessy, Carine; Viallon, Vivian; Siskos, Alexandros P; Dimou, Niki; Rinaldi, Sabina; Merritt, Melissa A; Allen, Naomi; Fortner, Renee; Kaaks, Rudolf; Weiderpass, Elisabete; Gram, Inger T; Rothwell, Joseph A; Lécuyer, Lucie; Severi, Gianluca; Schulze, Matthias B; Nøst, Therese Haugdahl; Crous-Bou, Marta; Sánchez, Maria-Jose; Amiano, Pilar; Colorado-Yohar, Sandra M; Gurrea, Aurelio Barricarte; Schmidt, Julie A; Palli, Domenico; Agnoli, Claudia; Tumino, Rosario; Sacerdote, Carlotta; Mattiello, Amalia; Vermeulen, Roel; Heath, Alicia K; Christakoudi, Sofia; Tsilidis, Konstantinos K; Travis, Ruth C; Gunter, Marc J; Keun, Hector C.
Affiliation
  • Dossus L; Nutrition and Metabolism Section, International Agency for Research on Cancer, Lyon, France. Electronic address: dossusl@iarc.fr.
  • Kouloura E; Cancer Metabolism and Systems Toxicology Group, Division of Cancer, Department of Surgery and Cancer, Imperial College, London, UK; European Food Safety Authority, Via Carlo Magno 1A, 43126 Parma, Italy.
  • Biessy C; Nutrition and Metabolism Section, International Agency for Research on Cancer, Lyon, France.
  • Viallon V; Nutrition and Metabolism Section, International Agency for Research on Cancer, Lyon, France.
  • Siskos AP; Cancer Metabolism and Systems Toxicology Group, Division of Cancer, Department of Surgery and Cancer, Imperial College, London, UK.
  • Dimou N; Nutrition and Metabolism Section, International Agency for Research on Cancer, Lyon, France.
  • Rinaldi S; Nutrition and Metabolism Section, International Agency for Research on Cancer, Lyon, France.
  • Merritt MA; Cancer Epidemiology Program, University of Hawaii Cancer Center, Honolulu, HI, USA.
  • Allen N; Nuffield Department of Population Health, University of Oxford, Oxford, UK.
  • Fortner R; Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
  • Kaaks R; Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
  • Weiderpass E; Office of the Director, International Agency for Research on Cancer, Lyon, France.
  • Gram IT; Department of Community Medicine, Faculty of Health Sciences, University of Tromsø, The Arctic University of Norway, Troms, Norway.
  • Rothwell JA; Centre for Research in Epidemiology and Population Health, CESP, Université Paris-Saclay, UVSQ, Inserm U1018, Villejuif, France; Gustave Roussy, Villejuif, France.
  • Lécuyer L; Centre for Research in Epidemiology and Population Health, CESP, Université Paris-Saclay, UVSQ, Inserm U1018, Villejuif, France; Gustave Roussy, Villejuif, France.
  • Severi G; Centre for Research in Epidemiology and Population Health, CESP, Université Paris-Saclay, UVSQ, Inserm U1018, Villejuif, France; Gustave Roussy, Villejuif, France; Department of Statistics, Computer Science and Applications "G. Parenti" (DISIA), University of Florence, Italy.
  • Schulze MB; Department of Molecular Epidemiology, German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany; Institute of Nutritional Science, University of Potsdam, Potsdam, Germany.
  • Nøst TH; Department of Community Medicine, Faculty of Health Sciences, University of Tromsø, The Arctic University of Norway, Troms, Norway.
  • Crous-Bou M; Unit of Nutrition and Cancer, Cancer Epidemiology Research Program, Catalan Institute of Oncology (ICO), Barcelona, Spain; Nutrition and Cancer Group, Bellvitge Biomedical Research Institute (IDIBELL), Barcelona, Spain; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston,US
  • Sánchez MJ; Escuela Andaluza de Salud Pública (EASP), Granada, Spain; Instituto de Investigación Biosanitaria ibs.GRANADA, Granada, Spain; Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública (CIBERESP), Madrid, Spain; Department of Preventive Medicine and Public Health, University of Grana
  • Amiano P; Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública (CIBERESP), Madrid, Spain; Public Health Division of Gipuzkoa, BioDonostia Research Institute, Donostia-San Sebastian, Spain.
  • Colorado-Yohar SM; Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública (CIBERESP), Madrid, Spain; Department of Epidemiology, Murcia Regional Health Council, IMIB-Arrixaca, Murcia, Spain; Research Group on Demography and Health, National Faculty of Public Health, University of Antioquia, Medellín
  • Gurrea AB; Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública (CIBERESP), Madrid, Spain; Navarra Public Health Institute, Pamplona, Spain; Navarra Institute for Health Research (IdiSNA) Pamplona, Spain.
  • Schmidt JA; Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, UK.
  • Palli D; Institute for Cancer Research, Prevention and Clinical Network - ISPRO, Cancer Risk Factors and Life-Style Epidemiology Unit, Florence, Italy.
  • Agnoli C; Epidemiology and Prevention Unit, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, Milano, Italy.
  • Tumino R; Cancer Registry and Histopathology Department, Provincial Health Authority (ASP) Ragusa, Italy.
  • Sacerdote C; Unit of Cancer Epidemiology, Città della Salute e della Scienza University-Hospital and Center for Cancer Prevention (CPO), Turin, Italy.
  • Mattiello A; Dipartimento di Medicina Clinica e Chirurgia, Federico II University, Naples, Italy.
  • Vermeulen R; Institute for Risk Assessment Sciences, Utrecht University, Utrecht, the Netherlands.
  • Heath AK; Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK.
  • Christakoudi S; Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK; MRC Centre for Transplantation, King's College London, London, UK.
  • Tsilidis KK; Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK; Department of Hygiene and Epidemiology, University of Ioannina School of Medicine, Ioannina, Greece.
  • Travis RC; Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, UK.
  • Gunter MJ; Nutrition and Metabolism Section, International Agency for Research on Cancer, Lyon, France.
  • Keun HC; Cancer Metabolism and Systems Toxicology Group, Division of Cancer, Department of Surgery and Cancer, Imperial College, London, UK.
Gynecol Oncol ; 162(2): 475-481, 2021 08.
Article in En | MEDLINE | ID: mdl-34099314
ABSTRACT

BACKGROUND:

Endometrial cancer is strongly associated with obesity and dysregulation of metabolic factors such as estrogen and insulin signaling are causal risk factors for this malignancy. To identify additional novel metabolic pathways associated with endometrial cancer we performed metabolomic analyses on pre-diagnostic plasma samples from 853 case-control pairs from the European Prospective Investigation into Cancer and Nutrition (EPIC).

METHODS:

A total of 129 metabolites (acylcarnitines, amino acids, biogenic amines, glycerophospholipids, hexoses, and sphingolipids) were measured by liquid chromatography-mass spectrometry. Conditional logistic regression estimated the associations of metabolites with endometrial cancer risk. An analysis focusing on clusters of metabolites using the bootstrap lasso method was also employed.

RESULTS:

After adjustment for body mass index, sphingomyelin [SM] C180 was positively (OR1SD 1.18, 95% CI 1.05-1.33), and glycine, serine, and free carnitine (C0) were inversely (OR1SD 0.89, 95% CI 0.80-0.99; OR1SD 0.89, 95% CI 0.79-1.00 and OR1SD 0.91, 95% CI 0.81-1.00, respectively) associated with endometrial cancer risk. Serine, C0 and two sphingomyelins were selected by the lasso method in >90% of the bootstrap samples. The ratio of esterified to free carnitine (OR1SD 1.14, 95% CI 1.02-1.28) and that of short chain to free acylcarnitines (OR1SD 1.12, 95% CI 1.00-1.25) were positively associated with endometrial cancer risk. Further adjustment for C-peptide or other endometrial cancer risk factors only minimally altered the results.

CONCLUSION:

These findings suggest that variation in levels of glycine, serine, SM C180 and free carnitine may represent specific pathways linked to endometrial cancer development. If causal, these pathways may offer novel targets for endometrial cancer prevention.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Biomarkers, Tumor / Endometrial Neoplasms Type of study: Clinical_trials / Etiology_studies / Observational_studies / Prognostic_studies / Risk_factors_studies Limits: Aged / Female / Humans / Middle aged Language: En Journal: Gynecol Oncol Year: 2021 Document type: Article
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Biomarkers, Tumor / Endometrial Neoplasms Type of study: Clinical_trials / Etiology_studies / Observational_studies / Prognostic_studies / Risk_factors_studies Limits: Aged / Female / Humans / Middle aged Language: En Journal: Gynecol Oncol Year: 2021 Document type: Article