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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 E. 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 Obesitat Trastorns del metabolisme Endometrial cancer Obesity 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. |
Note: | Reproducció del document publicat a: https://doi.org/10.1016/j.ygyno.2021.06.001 |
It is part of: | Gynecologic Oncology, 2021, vol. 162, num. 2, p. 475-481 |
URI: | http://hdl.handle.net/2445/179791 |
Related resource: | https://doi.org/10.1016/j.ygyno.2021.06.001 |
Appears in Collections: | Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL)) |
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