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.
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.
authors.forename: Krasimira
authors.initials: K
authors.lastname: Aleksandrova
authors.forename: Sabrina
authors.initials: S
authors.lastname: Schlesinger
authors.forename: Veronika
authors.initials: V
authors.lastname: Fedirko
authors.forename: Mazda
authors.initials: M
authors.lastname: Jenab
authors.forename: Bas
authors.initials: B
authors.lastname: Bueno-de-Mesquita
authors.forename: Heinz
authors.initials: H
authors.lastname: Freisling
authors.forename: Isabelle
authors.initials: I
authors.lastname: Romieu
authors.forename: Tobias
authors.initials: T
authors.lastname: Pischon
authors.forename: Rudolf
authors.initials: R
authors.lastname: Kaaks
authors.forename: Marc J
authors.initials: MJ
authors.lastname: Gunter
authors.forename: Christina C
authors.initials: CC
authors.lastname: Dahm
authors.forename: Kim
authors.initials: K
authors.lastname: Overvad
authors.forename: Agnetha Linn
authors.initials: AL
authors.lastname: Rostgaard-Hansen
authors.forename: Anne
authors.initials: A
authors.lastname: Tjønneland
authors.forename: Antonia
authors.initials: A
authors.lastname: Trichopoulou
authors.forename: Christina
authors.initials: C
authors.lastname: Bamia
authors.forename: Pagona
authors.initials: P
authors.lastname: Lagiou
authors.forename: Claudia
authors.initials: C
authors.lastname: Agnoli
authors.forename: Amalia
authors.initials: A
authors.lastname: Mattiello
authors.forename: Kathryn
authors.initials: K
authors.lastname: Bradbury
authors.forename: Kay-Tee
authors.initials: KT
authors.lastname: Khaw
authors.forename: Elio
authors.initials: E
authors.lastname: Riboli
authors.forename: Heiner
authors.initials: H
authors.lastname: Boeing
mesh_terms: D015415:Biomarkers; D001837:Body Weights and Measures; D016022:Case-Control Studies; D003110:Colonic Neoplasms / Q000453:epidemiology*; D004032:Diet; D005060:Europe / Q000453:epidemiology; D015444:Exercise; D005260:Female; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D018836:Inflammation Mediators / Q000097:blood; D007501:Iron / Q000378:metabolism; D008055:Lipids / Q000097:blood; D008297:Male; D008875:Middle Aged; D018384:Oxidative Stress / Q000502:physiology; D011446:Prospective Studies; D054411:Receptors, Leptin / Q000097:blood; D012004:Rectal Neoplasms / Q000453:epidemiology*; D012307:Risk Factors; D014807:Vitamin D / Q000378:metabolism; D015430:Weight Gain
chemical_list: D015415:Biomarkers; D006442:Glycated Hemoglobin; D018836:Inflammation Mediators; D007501:Iron; D008055:Lipids; D054411:Receptors, Leptin; D014807:Vitamin D
keywords: adiposity; adult weight gain; colorectal cancer; metabolic mediators