TY - JOUR AU - Kliemann, Nathalie AU - Viallon, Vivian AU - Murphy, Neil AU - Beeken, Rebecca J AU - Rothwell, Joseph A AU - Rinaldi, Sabina AU - Assi, Nada AU - van Roekel, Eline H AU - Schmidt, Julie A AU - Borch, Kristin Benjaminsen AU - Agnoli, Claudia AU - Rosendahl, Ann H AU - Sartor, Hanna AU - Huerta, José María AU - Tjønneland, Anne AU - Halkjær, Jytte AU - Bueno-de-Mesquita, Bas AU - Gicquiau, Audrey AU - Achaintre, David AU - Aleksandrova, Krasimira AU - Schulze, Matthias B AU - Heath, Alicia K AU - Tsilidis, Konstantinos K AU - Masala, Giovanna AU - Panico, Salvatore AU - Kaaks, Rudolf AU - Fortner, Renée T AU - Van Guelpen, Bethany AU - Dossus, Laure AU - Scalbert, Augustin AU - Keun, Hector C AU - Travis, Ruth C AU - Jenab, Mazda AU - Johansson, Mattias AU - Ferrari, Pietro AU - Gunter, Marc J TI - Metabolic signatures of greater body size and their associations with risk of colorectal and endometrial cancers in the European Prospective Investigation into Cancer and Nutrition. JO - BMC medicine VL - 19 IS - 1 SN - 1741-7015 CY - Heidelberg [u.a.] PB - Springer M1 - DKFZ-2021-00988 SP - 101 PY - 2021 AB - The 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 KW - Cancer (Other) KW - Metabolomics (Other) KW - Obesity (Other) KW - Weight loss (Other) LB - PUB:(DE-HGF)16 C6 - pmid:33926456 C2 - pmc:PMC8086283 DO - DOI:10.1186/s12916-021-01970-1 UR - https://inrepo02.dkfz.de/record/168680 ER -