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Physical activity, mediating factors and risk of colon cancer: insights into adiposity and circulating biomarkers from the EPIC cohort

Aleksandrova K 1 , Jenab M 2 , Leitzmann M 3 , Bueno-de-Mesquita B 4 , Kaaks R 5 , Trichopoulou A 6 Show all authors , Bamia C 6 , Lagiou P 6 , Rinaldi S 2 , Freisling H 2 , Carayol M 2 , Pischon T 7 , Drogan D 8 , Weiderpass E 9 , Jakszyn P 10 , Overvad K 11 , Dahm CC 11 , Tjønneland A 12 , Bouton-Ruault MC 13 , Kühn T 14 , Peppa E 6 , Valanou E 6 , La Vecchia C 6 , Palli D 15 , Panico S 16 , Sacerdote C 17 , Agnoli C 18 , Tumino R 19 , May A 20 , van Vulpen J 20 , Benjaminsen Borch K 9 , Oluwafemi Oyeyemi S 9 , Quirós JR 21 , Bonet C 10 , Sánchez MJ 22 , Dorronsoro M 23 , Navarro C 24 , Barricarte A 24 , van Guelpen B 25 , Wennberg P 26 , Key TJ 27 , Khaw KT 28 , Wareham N 29 , Assi N 2 , Ward HA 30 , Aune D 30 , Riboli E 30 , Boeing H 31

Affiliations 

  • 1 Nutrition, Immunity and Metabolism Start-up Lab, Department of Epidemiology, German Institute of Human Nutrition Potsdam-Rehbrücke, Nuthetal, Germany
  • 2 International Agency for Research on Cancer (IARC-WHO), Lyon, France
  • 3 Department of Epidemiology and Preventive Medicine, Regensburg University Medical Center, Regensburg, Germany
  • 4 National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands
  • 5 Division of Cancer Epidemiology, German Cancer Research Centre, Heidelberg, Germany
  • 6 Hellenic Health Foundation, Athens, Greece
  • 7 Molecular Epidemiology Group, Max Delbrueck Center for Molecular Medicine (MDC), Berlin-Buch, Germany
  • 8 Quality and Health Services Research Unit, AOK Research Institute, Berlin, Germany
  • 9 Department of Community Medicine, University of Tromsø, Tromsø, Norway
  • 10 Cancer Epidemiology Research Program, Catalan Institute of Oncology and Bellvitge Biomedical Research Institute, Barcelona, Spain
  • 11 Department of Public Health, Aarhus University, Aarhus, Denmark
  • 12 Diet, Genes and Environment, Danish Cancer Society Research Center, Copenhagen, Denmark
  • 13 Centre for Research in Epidemiology and Population Health, Villejuif, France
  • 14 German Cancer Research Center, Division of Cancer Epidemiology, Heidelberg, Germany
  • 15 Molecular and Nutritional Epidemiology Unit, Cancer Research and Prevention Institute, Florence, Italy
  • 16 Department of Clinical and Experimental Medicine, Federico II University, Naples, Italy
  • 17 Unit of Cancer Epidemiology, Città della Salute e della Scienza University-Hospital and Center for Cancer Prevention (CPO), Turin, Italy
  • 18 Fondazione IRCCS, Istituto Nazionale dei Tumori, Milan, Italy
  • 19 Cancer Registry and Histopathology Unit, 'M.P. Arezzo' Hospital, Ragusa, Italy
  • 20 Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands
  • 21 Public Health Directorate, Asturias, Oviedo, Spain
  • 22 Escuela Andaluza de Salud Pública. Instituto de Investigación Biosanitaria de Granada, Granada, Spain
  • 23 Public Health Division of Gipuzkoa, Basque Regional Health Department, San Sebastian, Spain
  • 24 Consortium for Biomedical Research in Epidemiology and Public Health, Madrid, Spain
  • 25 Department of Radiation Sciences Oncology, Umeå University, Umeå, Sweden
  • 26 Department of Public Health and Clinical Medicine, Family Medicine, Umeå University, Umeå, Sweden
  • 27 Nuffield Department of Population Health, University of Oxford, Oxford, UK
  • 28 Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK
  • 29 MRC Epidemiology Unit, Addenbrooke's Hospital, Cambridge, UK
  • 30 Division of Epidemiology, Public Health and Primary Care, Imperial College, London, UK
  • 31 Department of Epidemiology, German Institute of Human Nutrition Potsdam-Rehbrücke, Nuthetal, Germany
Int J Epidemiol, 2017 Dec 01;46(6):1823-1835.
PMID: 29025032 DOI: 10.1093/ije/dyx174

Abstract

BACKGROUND: There is convincing evidence that high physical activity lowers the risk of colon cancer; however, the underlying biological mechanisms remain largely unknown. We aimed to determine the extent to which body fatness and biomarkers of various biologically plausible pathways account for the association between physical activity and colon cancer.

METHODS: We conducted a nested case-control study in a cohort of 519 978 men and women aged 25 to 70 years followed from 1992 to 2003. A total of 713 incident colon cancer cases were matched, using risk-set sampling, to 713 controls on age, sex, study centre, fasting status and hormonal therapy use. The amount of total physical activity during the past year was expressed in metabolic equivalent of task [MET]-h/week. Anthropometric measurements and blood samples were collected at study baseline.

RESULTS: High physical activity was associated with a lower risk of colon cancer: relative risk ≥91 MET-h/week vs <91 MET-h/week = 0.75 [95% confidence interval (CI): 0.57 to 0.96]. In mediation analyses, this association was accounted for by waist circumference: proportion explained effect (PEE) = 17%; CI: 4% to 52%; and the biomarkers soluble leptin receptor (sOB-R): PEE = 15%; 95% CI: 1% to 50% and 5-hydroxyvitamin D (25[OH]D): PEE = 30%; 95% CI: 12% to 88%. In combination, these factors explained 45% (95% CI: 20% to 125%) of the association. Beyond waist circumference, sOB-R and 25[OH]D additionally explained 10% (95% CI: 1%; 56%) and 23% (95% CI: 6%; 111%) of the association, respectively.

CONCLUSIONS: Promoting physical activity, particularly outdoors, and maintaining metabolic health and adequate vitamin D levels could represent a promising strategy for colon cancer prevention.

* Title and MeSH Headings from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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