TY - JOUR
T1 - Prospective analysis of circulating metabolites and endometrial cancer risk
AU - Dossus, Laure
AU - Kouloura, Eirini
AU - Biessy, Carine
AU - Viallon, Vivian
AU - Siskos, Alexandros P.
AU - Dimou, Niki
AU - Rinaldi, Sabina
AU - Merritt, Melissa A.
AU - Allen, Naomi
AU - Fortner, Renee
AU - Kaaks, Rudolf
AU - Weiderpass, Elisabete
AU - Gram, Inger T.
AU - Rothwell, Joseph A.
AU - Lécuyer, Lucie
AU - Severi, Gianluca
AU - Schulze, Matthias B.
AU - Nøst, Therese Haugdahl
AU - Crous-Bou, Marta
AU - Sánchez, Maria Jose
AU - Amiano, Pilar
AU - Colorado-Yohar, Sandra M.
AU - Gurrea, Aurelio Barricarte
AU - Schmidt, Julie A.
AU - Palli, Domenico
AU - Agnoli, Claudia
AU - Tumino, Rosario
AU - Sacerdote, Carlotta
AU - Mattiello, Amalia
AU - Vermeulen, Roel
AU - Heath, Alicia K.
AU - Christakoudi, Sofia
AU - Tsilidis, Konstantinos K.
AU - Travis, Ruth C.
AU - Gunter, Marc J.
AU - Keun, Hector C.
N1 - Publisher Copyright:
© 2021
PY - 2021/8/1
Y1 - 2021/8/1
N2 - 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.
AB - 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.
KW - Amino acids
KW - Endometrial cancer
KW - Lipids
KW - Metabolomics
KW - Obesity
UR - http://www.scopus.com/inward/record.url?scp=85107389683&partnerID=8YFLogxK
U2 - 10.1016/j.ygyno.2021.06.001
DO - 10.1016/j.ygyno.2021.06.001
M3 - Article
C2 - 34099314
AN - SCOPUS:85107389683
SN - 0090-8258
VL - 162
SP - 475
EP - 481
JO - Gynecologic Oncology
JF - Gynecologic Oncology
IS - 2
ER -