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Title: Prospective analysis of circulating metabolites and endometrial cancer risk
Author: Dossus, Laure
Kouloura, Eirini
Biessy, Carine
Viallon, Vivian
Siskos, Alexandros P.
Dimou, Niki
Rinaldi, Sabina
Merritt, Melissa A.
Allen, Naomi
Fortner, Renee
Kaaks, Rudolf
Weiderpass, Elisabete
Gram, Inger T.
Rothwell, Joseph A.
Lécuyer, Lucie
Severi, Gianluca
Schulze, Matthias B.
Nøst, Therese Haugdahl
Crous Bou, Marta
Sánchez, Maria Jose
Amiano, Pilar
Colorado Yohar, Sandra M.
Barricarte Gurrea, Aurelio
Schmidt, Julie A.
Palli, Domenico
Agnoli, Claudia
Tumino, Rosario
Sacerdote, Carlotta
Mattiello, Amalia
Vermeulen, Roel
Heath, Alicia K.
Christakoudi, Sofia
Tsilidis, Konstantinos K.
Travis, Ruth C.
Gunter, Marc J.
Keun, Hector C.
Keywords: Càncer d'endometri
Trastorns del metabolisme
Endometrial cancer
Disorders of metabolism
Issue Date: 1-Aug-2021
Publisher: Elsevier BV
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 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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It is part of: Gynecologic Oncology, 2021, vol. 162, num. 2, p. 475-481
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Appears in Collections:Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))

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