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000168680 1001_ $$aKliemann, Nathalie$$b0
000168680 245__ $$aMetabolic signatures of greater body size and their associations with risk of colorectal and endometrial cancers in the European Prospective Investigation into Cancer and Nutrition.
000168680 260__ $$aHeidelberg [u.a.]$$bSpringer$$c2021
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000168680 520__ $$aThe mechanisms underlying the obesity-cancer relationship are incompletely understood. This study aimed to characterise metabolic signatures of greater body size and to investigate their association with two obesity-related malignancies, endometrial and colorectal cancers, and with weight loss within the context of an intervention study.Targeted mass spectrometry metabolomics data from 4326 participants enrolled in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort and 17 individuals from a single-arm pilot weight loss intervention (Intercept) were used in this analysis. Metabolic signatures of body size were first determined in discovery (N = 3029) and replication (N = 1297) sets among EPIC participants by testing the associations between 129 metabolites and body mass index (BMI), waist circumference (WC), and waist-to-hip ratio (WHR) using linear regression models followed by partial least squares analyses. Conditional logistic regression models assessed the associations between the metabolic signatures with endometrial (N = 635 cases and 648 controls) and colorectal (N = 423 cases and 423 controls) cancer risk using nested case-control studies in EPIC. Pearson correlation between changes in the metabolic signatures and weight loss was tested among Intercept participants.After adjustment for multiple comparisons, greater BMI, WC, and WHR were associated with higher levels of valine, isoleucine, glutamate, PC aa C38:3, and PC aa C38:4 and with lower levels of asparagine, glutamine, glycine, serine, lysoPC C17:0, lysoPC C18:1, lysoPC C18:2, PC aa C42:0, PC ae C34:3, PC ae C40:5, and PC ae C42:5. The metabolic signature of BMI (OR1-sd 1.50, 95% CI 1.30-1.74), WC (OR1-sd 1.46, 95% CI 1.27-1.69), and WHR (OR1-sd 1.54, 95% CI 1.33-1.79) were each associated with endometrial cancer risk. Risk of colorectal cancer was positively associated with the metabolic signature of WHR (OR1-sd: 1.26, 95% CI 1.07-1.49). In the Intercept study, a positive correlation was observed between weight loss and changes in the metabolic signatures of BMI (r = 0.5, 95% CI 0.06-0.94, p = 0.03), WC (r = 0.5, 95% CI 0.05-0.94, p = 0.03), and WHR (r = 0.6, 95% CI 0.32-0.87, p = 0.01).Obesity is associated with a distinct metabolic signature comprising changes in levels of specific amino acids and lipids which is positively associated with both colorectal and endometrial cancer and is potentially reversible following weight loss.
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000168680 650_7 $$2Other$$aCancer
000168680 650_7 $$2Other$$aMetabolomics
000168680 650_7 $$2Other$$aObesity
000168680 650_7 $$2Other$$aWeight loss
000168680 7001_ $$aViallon, Vivian$$b1
000168680 7001_ $$aMurphy, Neil$$b2
000168680 7001_ $$aBeeken, Rebecca J$$b3
000168680 7001_ $$aRothwell, Joseph A$$b4
000168680 7001_ $$aRinaldi, Sabina$$b5
000168680 7001_ $$aAssi, Nada$$b6
000168680 7001_ $$avan Roekel, Eline H$$b7
000168680 7001_ $$aSchmidt, Julie A$$b8
000168680 7001_ $$aBorch, Kristin Benjaminsen$$b9
000168680 7001_ $$aAgnoli, Claudia$$b10
000168680 7001_ $$aRosendahl, Ann H$$b11
000168680 7001_ $$aSartor, Hanna$$b12
000168680 7001_ $$aHuerta, José María$$b13
000168680 7001_ $$aTjønneland, Anne$$b14
000168680 7001_ $$aHalkjær, Jytte$$b15
000168680 7001_ $$aBueno-de-Mesquita, Bas$$b16
000168680 7001_ $$aGicquiau, Audrey$$b17
000168680 7001_ $$aAchaintre, David$$b18
000168680 7001_ $$aAleksandrova, Krasimira$$b19
000168680 7001_ $$aSchulze, Matthias B$$b20
000168680 7001_ $$aHeath, Alicia K$$b21
000168680 7001_ $$aTsilidis, Konstantinos K$$b22
000168680 7001_ $$aMasala, Giovanna$$b23
000168680 7001_ $$aPanico, Salvatore$$b24
000168680 7001_ $$0P:(DE-He78)4b2dc91c9d1ac33a1c0e0777d0c1697a$$aKaaks, Rudolf$$b25$$udkfz
000168680 7001_ $$0P:(DE-He78)74a6af8347ec5cbd4b77e562e10ca1f2$$aFortner, Renée T$$b26$$udkfz
000168680 7001_ $$aVan Guelpen, Bethany$$b27
000168680 7001_ $$aDossus, Laure$$b28
000168680 7001_ $$aScalbert, Augustin$$b29
000168680 7001_ $$aKeun, Hector C$$b30
000168680 7001_ $$aTravis, Ruth C$$b31
000168680 7001_ $$aJenab, Mazda$$b32
000168680 7001_ $$aJohansson, Mattias$$b33
000168680 7001_ $$aFerrari, Pietro$$b34
000168680 7001_ $$aGunter, Marc J$$b35
000168680 773__ $$0PERI:(DE-600)2131669-7$$a10.1186/s12916-021-01970-1$$gVol. 19, no. 1, p. 101$$n1$$p101$$tBMC medicine$$v19$$x1741-7015$$y2021
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