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@ARTICLE{Dossus:169139,
author = {L. Dossus and E. Kouloura and C. Biessy and V. Viallon and
A. P. Siskos and N. Dimou and S. Rinaldi and M. A. Merritt
and N. Allen and R. Fortner$^*$ and R. Kaaks$^*$ and E.
Weiderpass and I. T. Gram and J. A. Rothwell and L. Lécuyer
and G. Severi and M. B. Schulze and T. H. Nøst and M.
Crous-Bou and M.-J. Sánchez and P. Amiano and S. M.
Colorado-Yohar and A. B. Gurrea and J. A. Schmidt and D.
Palli and C. Agnoli and R. Tumino and C. Sacerdote and A.
Mattiello and R. Vermeulen and A. K. Heath and S.
Christakoudi and K. K. Tsilidis and R. C. Travis and M. J.
Gunter and H. C. Keun},
title = {{P}rospective analysis of circulating metabolites and
endometrial cancer risk.},
journal = {Gynecologic oncology},
volume = {162},
number = {2},
issn = {0090-8258},
address = {Amsterdam [u.a.]},
publisher = {Elsevier},
reportid = {DKFZ-2021-01281},
pages = {475-481},
year = {2021},
note = {2021 Aug;162(2):475-481},
abstract = {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).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.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.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 (Other) / Endometrial cancer (Other) / Lipids
(Other) / Metabolomics (Other) / Obesity (Other)},
cin = {C020},
ddc = {610},
cid = {I:(DE-He78)C020-20160331},
pnm = {313 - Krebsrisikofaktoren und Prävention (POF4-313)},
pid = {G:(DE-HGF)POF4-313},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:34099314},
doi = {10.1016/j.ygyno.2021.06.001},
url = {https://inrepo02.dkfz.de/record/169139},
}