1. Prospective analysis of circulating metabolites and endometrial cancer risk
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Alicia K Heath, Eirini Kouloura, Pilar Amiano, Joseph A. Rothwell, Marta Crous-Bou, Konstantinos K. Tsilidis, Melissa A. Merritt, Julie A. Schmidt, Lucie Lécuyer, María José Sánchez, Rosario Tumino, Domenico Palli, Hector C. Keun, Marc J. Gunter, Roel Vermeulen, Matthias B. Schulze, Inger T. Gram, Laure Dossus, Amalia Mattiello, Aurelio Barricarte Gurrea, Sandra Colorado-Yohar, Therese Haugdahl Nøst, Ruth C. Travis, Gianluca Severi, Carlotta Sacerdote, Claudia Agnoli, Naomi E. Allen, Elisabete Weiderpass, Alexandros P. Siskos, Carine Biessy, Vivian Viallon, Renée T. Fortner, Rudolf Kaaks, Niki Dimou, Sofia Christakoudi, Sabina Rinaldi, Sub Inorganic Chemistry and Catalysis, IRAS OH Epidemiology Chemical Agents, dIRAS RA-2, International Agency for Cancer Research (IACR), Imperial College London, European Food Safety Authority (EFSA), University of Hawai'i [Honolulu] (UH), Nuffield Department of Population Health [Oxford], University of Oxford [Oxford], German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ), University Hospital of North Norway [Tromsø] (UNN), Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, University of Potsdam, Harvard T.H. Chan School of Public Health, University of Granada [Granada], CIBER de Epidemiología y Salud Pública (CIBERESP), Institute for Cancer Research, Prevention and Clinical Network (ISPRO), IRCCS Istituto Nazionale dei Tumori [Milano], Provincial Health Authority (ASP 7) [Ragusa, Italy], University Hospital Città della Salute e della Scienza di Torino, University of Naples Federico II, Utrecht University [Utrecht], Kræftens Bekæmpelse, DCS, Deutsches Krebsforschungszentrum, DKFZ, Centre International de Recherche sur le Cancer, CIRC, Academy of Pharmaceutical Sciences, APS, National Research Council, NRC, Imperial Experimental Cancer Medicine Centre, ECMC, University of Maryland School of Public Health, SPH, Medical Research Council, MRC: MR/M012190/1, Cancer Research UK, CRUK: C19335/A21351, C8221/ A29017, World Cancer Research Fund, WCRF, Institut National de la Santé et de la Recherche Médicale, Inserm, Bundesministerium für Bildung und Forschung, BMBF, Cancerfonden, Ministerie van Volksgezondheid, Welzijn en Sport, VWS, Ligue Contre le Cancer, Vetenskapsrådet, VR, Instituto de Salud Carlos III, ISCIII, Associazione Italiana per la Ricerca sul Cancro, AIRC, Deutsche Krebshilfe, Institut Gustave-Roussy, Mutuelle Générale de l'Education Nationale, MGEN, NIHR Imperial Biomedical Research Centre, BRC, This work was supported by Cancer Research UK (CRUK) (grant number C19335/A21351, to MJG and HK).The metabolomics infrastructure in the Division of Cancer, Imperial College London is supported by the Imperial College Experimental Cancer Medicine Centre, the Imperial College Cancer Research UK Centre and the NIHR Imperial Biomedical Research Centre (APS & HK). The coordination of EPIC is financially supported by International Agency for Research on Cancer (IARC) and also by the Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London which has additional infrastructure support provided by the NIHR Imperial Biomedical Research Centre (BRC). The national cohorts are supported by: Danish Cancer Society (Denmark), Ligue Contre le Cancer, Institut Gustave Roussy, Mutuelle G?n?rale de l'Education Nationale, Institut National de la Sant? et de la Recherche M?dicale (INSERM) (France), German Cancer Aid, German Cancer Research Center (DKFZ), German Institute of Human Nutrition PotsdamRehbruecke (DIfE), Federal Ministry of Education and Research (BMBF) (Germany), Associazione Italiana per la Ricerca sul Cancro-AIRC-Italy, Compagnia di SanPaolo and National Research Council (Italy), Dutch Ministry of Public Health, Welfare and Sports (VWS), Netherlands Cancer Registry (NKR), LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund (WCRF), Statistics Netherlands (The Netherlands), Health Research Fund (FIS) - Instituto de Salud Carlos III (ISCIII), Regional Governments of Andaluc?a, Asturias, Basque Country, Murcia and Navarra, and the Catalan Institute of Oncology - ICO (Spain), Swedish Cancer Society, Swedish Research Council and County Councils of Sk?ne and V?sterbotten (Sweden), Cancer Research UK (14136 to EPIC-Norfolk, C8221/A29017 to EPIC-Oxford), Medical Research Council (1000143 to EPIC-Norfolk, MR/M012190/1 to EPIC-Oxford). (United Kingdom)., The metabolomics infrastructure in the Division of Cancer, Imperial College London is supported by the Imperial College Experimental Cancer Medicine Centre , the Imperial College Cancer Research UK Centre and the NIHR Imperial Biomedical Research Centre (APS & HK). The coordination of EPIC is financially supported by International Agency for Research on Cancer (IARC) and also by the Department of Epidemiology and Biostatistics , School of Public Health , Imperial College London which has additional infrastructure support provided by the NIHR Imperial Biomedical Research Centre (BRC) . The national cohorts are supported by: Danish Cancer Society (Denmark), Ligue Contre le Cancer , Institut Gustave Roussy , Mutuelle Générale de l'Education Nationale , Institut National de la Santé et de la Recherche Médicale (INSERM) (France), Dutch Ministry of Public Health, Welfare and Sports (VWS), Netherlands Cancer Registry (NKR), LK Research Funds , Dutch Prevention Funds , Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund (WCRF) , Statistics Netherlands (The Netherlands), Health Research Fund (FIS) - Instituto de Salud Carlos III (ISCIII) , Regional Governments of Andalucía, Asturias , Basque Country, Murcia and Navarra , and the Catalan Institute of Oncology - ICO (Spain), Swedish Cancer Society , Swedish Research Council and County Councils of Skåne and Västerbotten (Sweden), Cancer Research UK ( 14136 to EPIC-Norfolk, C8221/ A29017 to EPIC-Oxford), Medical Research Council ( 1000143 to EPIC-Norfolk, This work was supported by Cancer Research UK (CRUK) (grant number C19335/A21351 , to MJG and HK)., University of Oxford, University of Naples Federico II = Università degli studi di Napoli Federico II, Azienda Ospedalerio - Universitaria Città della Salute e della Scienza di Torino = University Hospital Città della Salute e della Scienza di Torino, Universidad de Granada = University of Granada (UGR), University of Potsdam = Universität Potsdam, HAL UVSQ, Équipe, Cancer Research UK, and Imperial College Healthcare NHS Trust- BRC Funding
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0301 basic medicine ,Trastorns del metabolisme ,[SDV]Life Sciences [q-bio] ,BMI, body mass index ,NIST, National Institute of Standards and Technology ,Body Mass Index ,Serine ,0302 clinical medicine ,Endometrial cancer ,Risk Factors ,WC, waist circumference ,LC-MS/MS, liquid chromatography-tandem mass spectrometry ,Prospective Studies ,2. Zero hunger ,SPHINGOMYELIN ,Endometrial Neoplasms/blood ,Sphingomyelins/blood ,Obstetrics & Gynecology ,Obstetrics and Gynecology ,C0, free carnitine ,Middle Aged ,Lipids ,MHT, menopausal hormone therapy ,AMINO-ACID ,Sphingomyelins ,3. Good health ,European Prospective Investigation into Cancer and Nutrition ,[SDV] Life Sciences [q-bio] ,Disorders of metabolism ,Oncology ,030220 oncology & carcinogenesis ,Obesitat ,Amino acids ,Tumor/blood ,NUTRITION ,Female ,ULOQ, upper limit of quantification ,Life Sciences & Biomedicine ,medicine.medical_specialty ,Carnitine/blood ,medicine.drug_class ,MODELS ,Glycine ,LLOQ, lower limit of quantification ,Glycine/blood ,Malignancy ,Article ,03 medical and health sciences ,Carnitine ,Internal medicine ,Biomarkers, Tumor ,medicine ,Humans ,Metabolomics ,1112 Oncology and Carcinogenesis ,Serine/blood ,Oncology & Carcinogenesis ,Obesity ,Aged ,SRM, standard reference material ,Science & Technology ,LOD, limit of detection ,SM, sphingomyelin ,EPIC, European Prospective Investigation into Cancer and Nutrition ,business.industry ,IARC, International Agency for Research on Cancer ,PROFILES ,Odds ratio ,medicine.disease ,SYNTHASES ,Sphingolipid ,Endometrial Neoplasms ,BODY-MASS INDEX ,CI, confidence interval ,OR, odds ratio ,030104 developmental biology ,Endocrinology ,Càncer d'endometri ,Estrogen ,Biomarkers, Tumor/blood ,Case-Control Studies ,1114 Paediatrics and Reproductive Medicine ,SD, standard deviation ,business ,CVs, coefficients of variation ,Body mass index ,Biomarkers - Abstract
This work was supported by Cancer Research UK (CRUK) (grant number C19335/A21351, to MJG and HK) . The metabolomics infrastructure in the Division of Cancer, Imperial College London is supported by the Imperial College Experimental Can-cer Medicine Centre, the This work was supported by Cancer Research UK (CRUK) (grant number C19335/A21351, to MJG and HK) . The metabolomics infrastructure in the Division of Cancer, Imperial College London is supported by the Imperial College Experimental Can-cer Medicine Centre, the Imperial College Cancer Research UK Centre and the NIHR Imperial Biomedical Research Centre (APS & HK) . The co-ordination of EPIC is financially supported by International Agency for Research on Cancer (IARC) and also by the Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London which has additional infrastructure support provided by the NIHR Im-perial Biomedical Research Centre (BRC) . The national cohorts are sup-ported by: Danish Cancer Society (Denmark) ; Ligue Contre le Cancer, Institut Gustave Roussy, Mutuelle Generale de l'Education Nationale, Institut National de la Sante et de la Recherche Medicale (INSERM) (France) ; German Cancer Aid, German Cancer Research Center (DKFZ) , German Institute of Human Nutrition PotsdamRehbruecke (DIfE) , Federal Ministry of Education and Research (BMBF) (Germany) ; Associazione Italiana per la Ricerca sul CancroAIRCItaly, Compagnia di SanPaolo and National Research Council (Italy) ; Dutch Ministry of Public Health, Welfare and Sports (VWS) , Netherlands Can-cer Registry (NKR) , LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland) , World Cancer Research Fund (WCRF) , Statistics Netherlands (The Netherlands) ; Health Research Fund (FIS) -Instituto de Salud Carlos III (ISCIII) , Regional Governments of Andalucia, Asturias, Basque Country, Murcia and Navarra, and the Catalan Institute of Oncology-ICO (Spain) ; Swedish Cancer Society, Swedish Research Council and County Councils of Skkne and Vasterbotten (Sweden) ; Cancer Research UK (14136 to EPICNorfolk; C8221/A29017 to EPICOxford) , Medical Research Council (1000143 to EPICNorfolk; MR/M012190/1 to EPICOxford) . (United Kingdom) ., 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 from853 case-control pairs fromthe European Prospective Investigation into Cancer and Nutrition (EPIC). Methods. A total of 129metabolites (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] C18:0was 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, SMC18:0 and free carnitine may represent specific pathways linked to endometrial cancer development. If causal, these pathways may offer novel targets for endometrial cancer prevention., Cancer Research UK C19335/A21351, Imperial College Experimental Cancer Medicine Centre Imperial College Cancer Research UK Centre, NIHR Imperial Biomedical Research Centre, World Health Organization, Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, Danish Cancer Society, Ligue Contre le Cancer (France) Institut Gustave Roussy (France) Mutuelle Generale de l'Education Nationale (France), Institut National de la Sante et de la Recherche Medicale (Inserm), Deutsche Krebshilfe, German Cancer Research Center (DKFZ) (Germany) German Institute of Human Nutrition PotsdamRehbruecke (DIfE) (Germany), Federal Ministry of Education & Research (BMBF), Fondazione AIRC per la ricerca sul cancro Compagnia di San Paolo Consiglio Nazionale delle Ricerche (CNR), Netherlands Government Netherlands Government, World Cancer Research Fund International (WCRF), Health Research Fund (FIS) - Instituto de Salud Carlos III (ISCIII) (Spain), Junta de Andalucia, Regional Government of Asturias (Spain), Regional Government of Basque Country (Spain), Regional Government of Murcia (Spain), Regional Government of Navarra (Spain), Catalan Institute of Oncology-ICO (Spain), Swedish Cancer Society, Swedish Research Council, County Council of Skkne (Sweden), County Council of Vasterbotten (Sweden), Cancer Research UK 14136 C8221/A29017, UK Research & Innovation (UKRI), Medical Research Council UK (MRC) 1000143 MR/M012190/1
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- 2021
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