@article{3108067,
    title = "Physical activity, mediating factors and risk of colon cancer: Insights into adiposity and circulating biomarkers from the EPIC cohort",
    author = "Aleksandrova, K. and Jenab, M. and Leitzmann, M. and Bueno-de-Mesquita, B. and Kaaks, R. and Trichopoulou, A. and Bamia, C. and Lagiou, P. and Rinaldi, S. and Freisling, H. and Carayol, M. and Pischon, T. and Drogan, D. and Weiderpass, E. and Jakszyn, P. and Overvad, K. and Dahm, C.C. and Tjønneland, A. and Bouton-Ruault, M.-C. and Kühn, T. and Peppa, E. and Valanou, E. and La Vecchia, C. and Palli, D. and Panico, S. and Sacerdote, C. and Agnoli, C. and Tumino, R. and May, A. and van Vulpen, J. and Borch, K.B. and Oyeyemi, S.O. and Quirós, J.R. and Bonet, C. and Sánchez, M.-J. and Dorronsoro, M. and Navarro, C. and Barricarte, A. and van Guelpen, B. and Wennberg, P. and Key, T.J. and Khaw, K.-T. and Wareham, N. and Assi, N. and Ward, H.A. and Aune, D. and Riboli, E. and Boeing, H.",
    journal = "International Journal of Epidemiology",
    year = "2017",
    volume = "46",
    number = "6",
    pages = "1823-1835",
    publisher = "Oxford University Press",
    issn = "0300-5771, 1464-3685",
    doi = "10.1093/ije/dyx174",
    keywords = "25 hydroxyvitamin D;  adiponectin;  C peptide;  C reactive protein;  cholesterol;  hemoglobin A1c;  high density lipoprotein cholesterol;  leptin;  leptin receptor;  low density lipoprotein cholesterol;  neopterin;  parathyroid hormone;  reactive oxygen metabolite;  somatomedin binding protein 1;  somatomedin binding protein 2;  somatomedin binding protein 3;  somatomedin C;  triacylglycerol;  tumor marker;  biological marker;  vitamin D, biomarker;  blood;  cancer;  cohort analysis;  confidence interval;  health risk;  muscle;  physical activity;  vitamin, adult;  aged;  anthropometry;  Article;  blood sampling;  body fat;  cancer incidence;  cancer risk;  case control study;  cholesterol blood level;  cohort analysis;  colon cancer;  diet restriction;  female;  ferric reducing antioxidant power assay;  hemoglobin blood level;  hormonal therapy;  human;  major clinical study;  male;  metabolic equivalent;  molecular weight;  obesity;  parathyroid hormone blood level;  physical activity;  priority journal;  risk factor;  triacylglycerol blood level;  vitamin D metabolism;  waist circumference;  blood;  body mass;  clinical trial;  colon tumor;  Europe;  exercise;  middle aged;  multicenter study;  obesity;  prospective study;  statistical model, Adiposity;  Adult;  Aged;  Biomarkers;  Body Mass Index;  Case-Control Studies;  Colonic Neoplasms;  Europe;  Exercise;  Female;  Humans;  Logistic Models;  Male;  Middle Aged;  Prospective Studies;  Risk Factors;  Vitamin D;  Waist Circumference",
    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. © The Author 2017."
}