TY - JOUR
T1 - Metabolic mediators of the association between adult weight gain and colorectal cancer
T2 - Data from the european prospective investigation into cancer and nutrition (EPIC) cohort
AU - Aleksandrova, Krasimira
AU - Schlesinger, Sabrina
AU - Fedirko, Veronika
AU - Jenab, Mazda
AU - Bueno-De-Mesquita, Bas
AU - Freisling, Heinz
AU - Romieu, Isabelle
AU - Pischon, Tobias
AU - Kaaks, Rudolf
AU - Gunter, Marc J.
AU - Dahm, Christina C.
AU - Overvad, Kim
AU - Rostgaard-Hansen, Agnetha Linn
AU - Tjønneland, Anne
AU - Trichopoulou, Antonia
AU - Bamia, Christina
AU - Lagiou, Pagona
AU - Agnoli, Claudia
AU - Mattiello, Amalia
AU - Bradbury, Kathryn
AU - Khaw, Kay Tee
AU - Riboli, Elio
AU - Boeing, Heiner
PY - 2017
Y1 - 2017
N2 - 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 (multivariableadjusted 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.
AB - 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 (multivariableadjusted 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.
KW - Adiposity
KW - Adult weight gain
KW - Colorectal cancer
KW - Metabolic mediators
U2 - 10.1093/aje/kww194
DO - 10.1093/aje/kww194
M3 - Journal article
C2 - 28387787
AN - SCOPUS:85020180717
SN - 0002-9262
VL - 185
SP - 751
EP - 764
JO - American Journal of Epidemiology
JF - American Journal of Epidemiology
IS - 9
ER -