Prospective analysis of circulating metabolites and endometrial cancer risk
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MetabolomicsAmino acidsLipidsEndometrial cancerObesity
Laure Dossus... [et al.]. Prospective analysis of circulating metabolites and endometrial cancer risk, Gynecologic Oncology, Volume 162, Issue 2, 2021, Pages 475-481, ISSN 0090-8258, [https://doi.org/10.1016/j.ygyno.2021.06.001]
SponsorshipCancer 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
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.