We found a match
Your institution may have rights to this item. Sign in to continue.
- Title
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.
- Authors
Kliemann, Nathalie; Viallon, Vivian; Murphy, Neil; Beeken, Rebecca J.; Rothwell, Joseph A.; Rinaldi, Sabina; Assi, Nada; van Roekel, Eline H.; Schmidt, Julie A.; Borch, Kristin Benjaminsen; Agnoli, Claudia; Rosendahl, Ann H.; Sartor, Hanna; Huerta, José María; Tjønneland, Anne; Halkjær, Jytte; Bueno-de-Mesquita, Bas; Gicquiau, Audrey; Achaintre, David; Aleksandrova, Krasimira
- Abstract
<bold>Background: </bold>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.<bold>Methods: </bold>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.<bold>Results: </bold>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).<bold>Conclusions: </bold>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.
- Subjects
BODY size; ENDOMETRIAL cancer; COLORECTAL cancer; WAIST-hip ratio; BODY mass index; RESEARCH; RESEARCH methodology; MEDICAL cooperation; EVALUATION research; COMPARATIVE studies; ENDOMETRIAL tumors; WAIST circumference; RESEARCH funding; LOGISTIC regression analysis; LONGITUDINAL method
- Publication
BMC Medicine, 2021, Vol 19, Issue 1, p1
- ISSN
1741-7015
- Publication type
journal article
- DOI
10.1186/s12916-021-01970-1