@misc{10481/70329,
year = {2021},
month = {6},
url = {http://hdl.handle.net/10481/70329},
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 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.},
organization = {Cancer Research UK	C19335/A21351},
organization = {Imperial College Experimental Cancer Medicine Centre		
Imperial College Cancer Research UK Centre},
organization = {NIHR Imperial Biomedical Research Centre},
organization = {World Health Organization},
organization = {Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London},
organization = {Danish Cancer Society},
organization = {Ligue Contre le Cancer (France)		
Institut Gustave Roussy (France)		
Mutuelle Generale de l'Education Nationale (France)},
organization = {Institut National de la Sante et de la Recherche Medicale (Inserm)},
organization = {Deutsche Krebshilfe},
organization = {German Cancer Research Center (DKFZ) (Germany)		
German Institute of Human Nutrition PotsdamRehbruecke (DIfE) (Germany)},
organization = {Federal Ministry of Education & Research (BMBF)},
organization = {Fondazione AIRC per la ricerca sul cancro		
Compagnia di San Paolo		
Consiglio Nazionale delle Ricerche (CNR)},
organization = {Netherlands Government		
Netherlands Government},
organization = {World Cancer Research Fund International (WCRF)},
organization = {Health Research Fund (FIS) - Instituto de Salud Carlos III (ISCIII) (Spain)},
organization = {Junta de Andalucia},
organization = {Regional Government of Asturias (Spain)},
organization = {Regional Government of Basque Country (Spain)},
organization = {Regional Government of Murcia (Spain)},
organization = {Regional Government of Navarra (Spain)},
organization = {Catalan Institute of Oncology-ICO (Spain)},
organization = {Swedish Cancer Society},
organization = {Swedish Research Council},
organization = {County Council of Skkne (Sweden)},
organization = {County Council of Vasterbotten (Sweden)},
organization = {Cancer Research UK	14136	
C8221/A29017},
organization = {UK Research & Innovation (UKRI)},
organization = {Medical Research Council UK (MRC)	1000143	
MR/M012190/1},
publisher = {Elsevier},
keywords = {Metabolomics},
keywords = {Amino acids},
keywords = {Lipids},
keywords = {Endometrial cancer},
keywords = {Obesity},
title = {Prospective analysis of circulating metabolites and endometrial cancer risk},
doi = {10.1016/j.ygyno.2021.06.001},
author = {Dossus, Laure and Sánchez Pérez, María José},
}