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dc.contributor.authorDossus, Laure
dc.contributor.authorKouloura, Eirini
dc.contributor.authorBiessy, Carine
dc.contributor.authorViallon, Vivian
dc.contributor.authorSiskos, Alexandros P.
dc.contributor.authorDimou, Niki
dc.contributor.authorRinaldi, Sabina
dc.contributor.authorMerritt, Melissa A.
dc.contributor.authorAllen, Naomi E.
dc.contributor.authorFortner, Renée T.
dc.contributor.authorKaaks, Rudolf
dc.contributor.authorWeiderpass, Elisabete
dc.contributor.authorGram, Inger Torhild
dc.contributor.authorRothwell, Joseph A.
dc.contributor.authorLécuyer, Lucie
dc.contributor.authorSeveri, Gianluca
dc.contributor.authorSchulze, Matthias B.
dc.contributor.authorNøst, Therese Haugdahl
dc.contributor.authorCrous-Bou, Marta
dc.contributor.authorSánchez, Maria-Jose
dc.contributor.authorAmiano, Pilar
dc.contributor.authorColorado-Yohar, Sandra
dc.contributor.authorBarricarte, Aurelio
dc.contributor.authorSchmidt, Julie A.
dc.contributor.authorPalli, Domenico
dc.contributor.authorAgnoli, Claudia
dc.contributor.authorTumino, Rosario
dc.contributor.authorSacerdote, Carlotta
dc.contributor.authorMattiello, Amalia
dc.contributor.authorVermeulen, Roel
dc.contributor.authorHeath, Alicia K.
dc.contributor.authorChristakoudi, Sofia
dc.contributor.authorTsilidis, Konstantinos K.
dc.contributor.authorTravis, Ruth C.
dc.contributor.authorGunter, Marc J.
dc.contributor.authorKeun, Hector C.
dc.date.accessioned2022-03-07T08:07:56Z
dc.date.available2022-03-07T08:07:56Z
dc.date.issued2021-06-05
dc.description.abstractBackground. 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).<p> 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.<p> Results. After adjustment for body mass index, sphingomyelin [SM] C18:0 was positively (OR<sub>1SD</sub>: 1.18, 95% CI: 1.05–1.33), and glycine, serine, and free carnitine (C0) were inversely (OR<sub>1SD</sub>: 0.89, 95% CI: 0.80–0.99; OR<sub>1SD</sub>: 0.89, 95% CI: 0.79–1.00 and OR<sub>1SD</sub>: 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 (OR<sub>1SD</sub>: 1.14, 95% CI: 1.02–1.28) and that of short chain to free acylcarnitines (OR<sub>1SD</sub>: 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.<p> 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.en_US
dc.identifier.citationDossus, Kouloura, Biessy, Viallon, Siskos, Dimou, Rinaldi, Merritt, Allen, Fortner, Kaaks, Weiderpass, Gram, Rothwell, Lécuyer, Severi, Schulze, Nøst, Crous-Bou, Sánchez, Amiano, Colorado-Yohar, Barricarte, Schmidt, Palli, Agnoli, Tumino, Sacerdote, Mattiello, Vermeulen, Heath, Christakoudi, Tsilidis, Travis, Gunter, Keun. Prospective analysis of circulating metabolites and endometrial cancer risk. Gynecologic Oncology. 2021;162(2):475-481en_US
dc.identifier.cristinIDFRIDAID 2006135
dc.identifier.doi10.1016/j.ygyno.2021.06.001
dc.identifier.issn0090-8258
dc.identifier.issn1095-6859
dc.identifier.urihttps://hdl.handle.net/10037/24279
dc.language.isoengen_US
dc.publisherElsevieren_US
dc.relation.journalGynecologic Oncology
dc.rights.accessRightsopenAccessen_US
dc.rights.holderCopyright 2021 Elsevieren_US
dc.titleProspective analysis of circulating metabolites and endometrial cancer risken_US
dc.type.versionpublishedVersionen_US
dc.typeJournal articleen_US
dc.typeTidsskriftartikkelen_US
dc.typePeer revieweden_US


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