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Metabolic Mediators of the Association Between Adult Weight Gain and Colorectal Cancer: Data From the European Prospective Investigation Into Cancer and Nutrition (EPIC) Cohort

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Title: Metabolic Mediators of the Association Between Adult Weight Gain and Colorectal Cancer: Data From the European Prospective Investigation Into Cancer and Nutrition (EPIC) Cohort
Authors: Aleksandrova, K
Schlesinger, S
Fedirko, V
Jenab, M
Bueno-de-Mesquita, B
Freisling, H
Romieu, I
Pischon, T
Kaaks, R
Gunter, MJ
Dahm, CC
Overvad, K
Rostgaard-Hansen, AL
Tjonneland, A
Trichopoulou, A
Bamia, C
Lagiou, P
Agnoli, C
Mattiello, A
Bradbury, K
Khaw, K-T
Riboli, E
Boeing, H
Item Type: Journal Article
Abstract: Evidence indicates that gaining weight in adult life is associated with an elevated risk of colorectal cancer; however, biological mechanisms that may explain this association remain unclear. We evaluated the mediation effect of 20 different biomarkers on the relationship between adult weight gain and colorectal cancer, using data from a prospective nested case-control study of 452 incident cases diagnosed between 1992 and 2003 and matched within risk sets to 452 controls within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. The proportions of mediated effects (%) were estimated on the basis of differences in percent effect changes in conditional logistic regression models with and without additional adjustment for individual biomarkers. Greater adult weight gain (≥300 g/year vs. <300 g/year) was associated with a higher risk of colon cancer (multivariable-adjusted relative risk = 1.54, 95% confidence interval: 1.07, 2.24) but not rectal cancer (relative risk = 1.07, 95% confidence interval: 0.68, 1.66). This association was accounted for mostly by attained waist circumference (reduction of 61%) and by the biomarkers soluble leptin receptor (reduction of 43%) and glycated hemoglobin (reduction of 28%). These novel data suggest that the observed association between adult weight gain and colon cancer could be primarily explained by attained abdominal fatness and biomarkers of metabolic dysfunction.
Issue Date: 6-Apr-2017
Date of Acceptance: 1-Apr-2016
URI: http://hdl.handle.net/10044/1/48850
DOI: https://dx.doi.org/10.1093/aje/kww194
ISSN: 0002-9262
Publisher: Oxford University Press
Start Page: 751
End Page: 764
Journal / Book Title: AMERICAN JOURNAL OF EPIDEMIOLOGY
Volume: 185
Issue: 9
Copyright Statement: © 2017 The Author(s). Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com. This is a pre-copy-editing, author-produced version of an article accepted for publication in American Journal of Epidemiology following peer review. The definitive publisher-authenticated version Krasimira Aleksandrova, Sabrina Schlesinger, Veronika Fedirko, Mazda Jenab, Bas Bueno-de-Mesquita, Heinz Freisling, Isabelle Romieu, Tobias Pischon, Rudolf Kaaks, Marc J. Gunter, Christina C. Dahm, Kim Overvad, Agnetha Linn Rostgaard-Hansen, Anne Tjønneland, Antonia Trichopoulou, Christina Bamia, Pagona Lagiou, Claudia Agnoli, Amalia Mattiello, Kathryn Bradbury, Kay-Tee Khaw, Elio Riboli, Heiner Boeing; Metabolic Mediators of the Association Between Adult Weight Gain and Colorectal Cancer: Data From the European Prospective Investigation into Cancer and Nutrition (EPIC) Cohort. Am J Epidemiol 2017; 185 (9): 751-764. doi: 10.1093/aje/kww194 is available online at: https://dx.doi.org/10.1093/aje/kww194
Keywords: Science & Technology
Life Sciences & Biomedicine
Public, Environmental & Occupational Health
adiposity
adult weight gain
colorectal cancer
metabolic mediators
SOLUBLE LEPTIN RECEPTOR
C-REACTIVE PROTEIN
OXIDATIVE STRESS
VITAMIN-D
RISK
METAANALYSIS
IMMUNITY
IRON
POPULATIONS
BIOMARKERS
Epidemiology
11 Medical And Health Sciences
01 Mathematical Sciences
Publication Status: Published
Appears in Collections:Faculty of Medicine
Epidemiology, Public Health and Primary Care



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