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Observational Study
. 2021 Aug;162(2):475-481.
doi: 10.1016/j.ygyno.2021.06.001. Epub 2021 Jun 5.

Prospective analysis of circulating metabolites and endometrial cancer risk

Laure Dossus  1 , Eirini Kouloura  2 , Carine Biessy  3 , Vivian Viallon  3 , Alexandros P Siskos  4 , Niki Dimou  3 , Sabina Rinaldi  3 , Melissa A Merritt  5 , Naomi Allen  6 , Renee Fortner  7 , Rudolf Kaaks  7 , Elisabete Weiderpass  8 , Inger T Gram  9 , Joseph A Rothwell  10 , Lucie Lécuyer  10 , Gianluca Severi  11 , Matthias B Schulze  12 , Therese Haugdahl Nøst  9 , Marta Crous-Bou  13 , Maria-Jose Sánchez  14 , Pilar Amiano  15 , Sandra M Colorado-Yohar  16 , Aurelio Barricarte Gurrea  17 , Julie A Schmidt  18 , Domenico Palli  19 , Claudia Agnoli  20 , Rosario Tumino  21 , Carlotta Sacerdote  22 , Amalia Mattiello  23 , Roel Vermeulen  24 , Alicia K Heath  25 , Sofia Christakoudi  26 , Konstantinos K Tsilidis  27 , Ruth C Travis  18 , Marc J Gunter  3 , Hector C Keun  4
Affiliations
Observational Study

Prospective analysis of circulating metabolites and endometrial cancer risk

Laure Dossus et al. Gynecol Oncol. 2021 Aug.

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.

Keywords: Amino acids; Endometrial cancer; Lipids; Metabolomics; Obesity.

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Conflict of interest statement

Declaration of Competing Interest None.

Figures

Fig. 1
Fig. 1
Odds ratios (ORs) and P-values for the associations between metabolites and risk of endometrial cancer in (A) unadjusted models (B) BMI-adjusted models. PC: phosphatidylcholine; SM: sphingomyelin. ORs are estimated per standard deviation (SD) increase in log-transformed metabolite concentrations, from logistic regression conditional on matching variables. Figs. A and B shows statistical significance based on P-values (significant metabolites above dotted line).
Fig. 2
Fig. 2
Odds ratios (ORs) and P-values for the associations between metabolite ratios and risk of endometrial cancer in (A) unadjusted models (B) BMI-adjusted models. ORs are estimated per standard deviation (SD) increase in log-transformed metabolite concentrations, from logistic regression conditional on matching variables. Figs. A and B shows statistical significance based on P-values (significant metabolites above dotted line).
See this image and copyright information in PMC

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