Adiposity, mediating biomarkers and risk of colon cancer in the European prospective investigation into cancer and nutrition study

Krasimira Aleksandrova, Dagmar Drogan, Heiner Boeing, Mazda Jenab, H. Bas Bueno-De-Mesquita, Eugene Jansen, Fränzel J B Van Duijnhoven, Sabina Rinaldi, Veronika Fedirko, Isabelle Romieu, Rudolf Kaaks, Elio Riboli, Marc J. Gunter, Dora Romaguera, Sabine Westhpal, Kim Overvad, Anne Tjønneland, Jytte Halkjær, Marie Christine Boutron-Ruault, Françoise Clavel-ChapelonAnnekatrin Lukanova, Antonia Trichopoulou, Dimitrios Trichopoulos, Pavlos Vidalis, Salvatore Panico, Claudia Agnoli, Domenico Palli, Rosario Tumino, Paolo Vineis, Genevieve Buckland, José Juan Sánchez-Cruz, Miren Dorronsoro, María José Tormo Díaz, Aurelio Barricarte, J. Ramon Quiros, Petra H. Peeters, Anne M. May, Göran Hallmans, Richard Palmqvist, Francesca L. Crowe, Kay Tee Khaw, Nickolas Wareham, Tobias Pischon

Research output: Contribution to journalArticle

Abstract

Adiposity is a risk factor for colon cancer, but underlying mechanisms are not well understood. We evaluated the extent to which 11 biomarkers with inflammatory and metabolic actions mediate the association of adiposity measures, waist circumference (WC) and body mass index (BMI), with colon cancer in men and women. We analyzed data from a prospective nested case-control study among 662 incident colon cancer cases matched within risk sets to 662 controls. Relative risks (RRs) and 95% confidence intervals (CIs) were calculated using conditional logistic regression. The percent effect change and corresponding CIs were estimated after adjusting for biomarkers shown to be associated with colon cancer risk. After multivariable adjustment, WC was associated with colon cancer risk in men (top vs. bottom tertile RR 1.68, 95% CI 1.06-2.65; p trend = 0.02) and in women (RR 1.67, 95% CI 1.09-2.56; p trend = 0.03). BMI was associated with risk only in men. The association of WC with colon cancer was accounted mostly for by three biomarkers, high-density lipoprotein cholesterol, non-high-molecular-weight adiponectin and soluble leptin receptor, which in combination explained 46% (95% CI 37-57%) of the association in men and 50% (95% CI 40-65%) of the association in women. Similar results were observed for the associations with BMI in men. These data suggest that alterations in levels of these metabolic biomarkers may represent a primary mechanism of action in the relation of adiposity with colon cancer. Further studies are warranted to determine whether altering their concentrations may reduce colon cancer risk.

Original languageEnglish
Pages (from-to)612-621
Number of pages10
JournalInternational Journal of Cancer
Volume134
Issue number3
DOIs
Publication statusPublished - 2013

Keywords

  • adiposity
  • body mass index
  • colon cancer
  • mediating biomarkers
  • waist circumference

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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