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

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Title: Physical activity, mediating factors and risk of colon cancer: insights into adiposity and circulating biomarkers from the EPIC Cohort
Authors: Aleksandrova, K
Jenab, M
Leitzmann, M
Bueno-d-Mesquita, B
Kaaks, R
Trichopoulou, A
Bamia, C
Lagiou, P
Rinaldi, S
Freisling, H
Carayol, M
Pischon, T
Drogan, D
Weiderpass, E
Jakszyn, P
Overvad, K
Dahm, CC
Tjonneland, A
Bouton-Ruault, M-C
Kuhn, T
Peppa, E
Valanou, E
La Vecchia, C
Palli, D
Panico, S
Sacerdote, C
Agnoli, C
Tumino, R
May, A
Van Vulpen, J
Benjaminsen Borch, K
Oluwafemi Oyeyemi, S
Quiros, JR
Bonet, C
Sanchez, M-J
Dorronsoro, M
Navarro, C
Barricarte, A
Van Guelpen, B
Wennberg, P
Key, TJ
Khaw, K-T
Wareham, N
Assi, N
Ward, HA
Aune, D
Riboli, E
Boeing, H
Item Type: Journal Article
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.
Issue Date: 5-Sep-2017
Date of Acceptance: 26-Jul-2017
ISSN: 1464-3685
Publisher: Oxford University Press (OUP)
Start Page: 1823
End Page: 1835
Journal / Book Title: International Journal of Epidemiology
Volume: 46
Issue: 6
Copyright Statement: This is a pre-copyedited, author-produced PDF of an article accepted for publication in International Journal of Epidemiology following peer review. The version of record Krasimira Aleksandrova, Mazda Jenab, Michael Leitzmann, Bas Bueno-de-Mesquita, Rudolf Kaaks, Antonia Trichopoulou, Christina Bamia, Pagona Lagiou, Sabina Rinaldi, Heinz Freisling, Marion Carayol, Tobias Pischon, Dagmar Drogan, Elisabete Weiderpass, Paula Jakszyn, Kim Overvad, Christina C Dahm, Anne Tjønneland, Marie-Christine Bouton-Ruault, Tilman Kühn, Eleni Peppa, Elissavet Valanou, Carlo La Vecchia, Domenico Palli, Salvatore Panico, Carlotta Sacerdote, Claudia Agnoli, Rosario Tumino, Anne May, Jonna van Vulpen, Kristin Benjaminsen Borch, Sunday Oluwafemi Oyeyemi, J Ramón Quirós, Catalina Bonet, María-José Sánchez, Miren Dorronsoro, Carmen Navarro, Aurelio Barricarte, Bethany van Guelpen, Patrik Wennberg, Timothy J Key, Kay-Tee Khaw, Nicholas Wareham, Nada Assi, Heather A Ward, Dagfinn Aune, Elio Riboli, Heiner Boeing; Physical activity, mediating factors and risk of colon cancer: insights into adiposity and circulating biomarkers from the EPIC cohort, International Journal of Epidemiology, , dyx174, is available online at:
Sponsor/Funder: Imperial College Trust
Funder's Grant Number: P47328
Keywords: Science & Technology
Life Sciences & Biomedicine
Public, Environmental & Occupational Health
Physical activity
colon cancer
mediating factors
0104 Statistics
1117 Public Health And Health Services
Publication Status: Published
Appears in Collections:Faculty of Medicine
Epidemiology, Public Health and Primary Care

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