Metabolic mediators of the association between adult weight gain and colorectal cancer: Data from the european prospective investigation into cancer and nutrition (EPIC) cohort

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 BradburyKay Tee Khaw, Elio Riboli, Heiner Boeing

Research output: Contribution to journalArticle

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 (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.

Original languageEnglish
Pages (from-to)751-764
Number of pages14
JournalAmerican Journal of Epidemiology
Volume185
Issue number9
DOIs
Publication statusPublished - May 1 2017

Keywords

  • Adiposity
  • Adult weight gain
  • Colorectal cancer
  • Metabolic mediators

ASJC Scopus subject areas

  • Epidemiology

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    Aleksandrova, K., Schlesinger, S., Fedirko, V., Jenab, M., Bueno-De-Mesquita, B., Freisling, H., Romieu, I., Pischon, T., Kaaks, R., Gunter, M. J., Dahm, C. C., Overvad, K., Rostgaard-Hansen, A. L., Tjønneland, A., Trichopoulou, A., Bamia, C., Lagiou, P., Agnoli, C., Mattiello, A., ... Boeing, H. (2017). Metabolic mediators of the association between adult weight gain and colorectal cancer: Data from the european prospective investigation into cancer and nutrition (EPIC) cohort. American Journal of Epidemiology, 185(9), 751-764. https://doi.org/10.1093/aje/kww194