Prospective analysis of circulating metabolites and endometrial cancer risk
Dossus, L.; Kouloura, E.; Biessy, C.; Viallon, V.; Siskos, A.P.; Dimou, N.; Rinaldi, S.; Merritt, M.A.; Allen, N.; Fortner, R.; Kaaks, R.; Weiderpass, E.; Gram, I.T.; Rothwell, J.A.; Lécuyer, L.; Severi, G.; Schulze, M.B.; Nøst, T.H.; Crous-Bou, M.; Sánchez, M.-J.; Amiano, P.; Colorado-Yohar, S.M.; Gurrea, A.B.; Schmidt, J.A.; Palli, D.; Agnoli, C.; Tumino, R.; Sacerdote, C.; Mattiello, A.; Vermeulen, R.; Heath, A.K.; Christakoudi, S.; Tsilidis, K.K.; Travis, R.C.; Gunter, M.J.; Keun, H.C.
(2021) Gynecologic Oncology, volume 162, issue 2, pp. 475 - 481
(Article)
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
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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] C18:0 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 C18:0 and free carnitine may represent specific pathways linked to endometrial cancer development. If causal, these pathways may offer novel targets for endometrial cancer prevention.
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Keywords: Aged, Biomarkers, Tumor/blood, Body Mass Index, Carnitine/blood, Case-Control Studies, Endometrial Neoplasms/blood, Female, Glycine/blood, Humans, Metabolomics, Middle Aged, Prospective Studies, Risk Factors, Serine/blood, Sphingomyelins/blood
ISSN: 0090-8258
Publisher: Academic Press Inc.
Note: Funding Information: 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). Funding Information: 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); 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 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; MR/M012190/1 to EPIC-Oxford). (United Kingdom). Funding Information: This work was supported by Cancer Research UK (CRUK) (grant number C19335/A21351 , to MJG and HK). Publisher Copyright: © 2021
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