Physical activity, obesity and sedentary behavior in cancer etiology: epidemiologic evidence and biologic mechanisms

Christine M Friedenreich, Charlotte Ryder-Burbidge, Jessica McNeil, Christine M Friedenreich, Charlotte Ryder-Burbidge, Jessica McNeil

Abstract

An estimated 30-40% of cancers can be prevented through changes in modifiable lifestyle and environmental risk factors known to be associated with cancer incidence. Despite this knowledge, there remains limited awareness that these associations exist. The purpose of this review article was to summarize the epidemiologic evidence concerning the contribution of physical activity, sedentary behavior, and obesity to cancer etiology and to provide an overview of the biologic mechanisms that may be operative between these factors and cancer incidence. Strong and consistent evidence exists that higher levels of physical activity reduce the risk of six different cancer sites (bladder, breast, colon, endometrial, esophageal adenocarcinoma, gastric cardia), whereas moderate evidence inversely associates physical activity with lung, ovarian, pancreatic and renal cancer, and limited evidence inversely correlates physical activity with prostate cancer. Sedentary behavior, independent of physical activity, has been shown to increase the risk of colon, endometrial, and lung cancers. Obesity is an established risk factor for 13 different cancer sites (endometrial, postmenopausal breast, colorectal, esophageal, renal/kidneys, meningioma, pancreatic, gastric cardia, liver, multiple myeloma, ovarian, gallbladder, and thyroid). The main biologic mechanisms whereby physical activity, sedentary behavior, and obesity are related to cancer incidence include an effect on endogenous sex steroids and metabolic hormones, insulin sensitivity, and chronic inflammation. Several emerging pathways related to oxidative stress, DNA methylation, telomere length, immune function, and gut microbiome are presented. Key recommendations for future research in both the epidemiology and biology of the associations between physical activity, sedentary behavior, obesity, and cancer risk are also provided.

Keywords: chronic inflammation; hormone; metabolism; obesity; physical activity; sedentary behavior.

Conflict of interest statement

The authors declare no conflict of interest.

© 2020 The Authors. Published by FEBS Press and John Wiley & Sons Ltd.

Figures

Fig. 1
Fig. 1
Hypothesized biologic mechanisms linking physical activity, excess body fat, and sedentary behavior to cancer risk. IGF‐1, insulin‐like growth factor‐1; IGFBP‐3, insulin growth factor‐binding protein‐3; IL‐6, interleukin‐6; TNF‐α, tumor necrosis factor‐α; IL‐1β, interleukin‐1β; CRP, C‐reactive protein; SAA, serum amyloid A; SHBG, sex hormone‐binding globulin.

References

    1. Kulhánová I, Znaor A, Shield KD, Arnold M, Vignat J, Charafeddine M, Fadhil I, Fouad H, Al‐Omari A, Al‐Zahrani AS et al. (2020) Proportion of cancers attributable to major lifestyle and environmental risk factors in the Eastern Mediterranean region. Int J Cancer 146, 646–656.
    1. Parkin DM, Boyd L & Walker LC (2011) The fraction of cancer attributable to lifestyle and environmental factors in the UK in 2010. Br J Cancer 105, S77–S81.
    1. Poirier AE, Ruan Y, Volesky KD, King WD, O'Sullivan DE, Gogna P, Walter SD, Villeneuve PJ, Friedenreich CM & Brenner DR (2019) The current and future burden of cancer attributable to modifiable risk factors in Canada: summary of results. Prev Med 122, 140–147.
    1. Whiteman DC, Webb PM, Green AC, Neale RE, Fritschi L, Bain CJ, Parkin DM, Wilson LF, Olsen CM, Nagle CM et al. (2015) Cancers in Australia in 2010 attributable to modifiable factors: summary and conclusions. Aust N Z J Public Health 39, 477–484.
    1. Ding D, Lawson KD, Kolbe‐Alexander TL, Finkelstein EA, Katzmarzyk PT, van Mechelen W & Pratt M (2016) The economic burden of physical inactivity: a global analysis of major non‐communicable diseases. Lancet 388, 1311–1324.
    1. Guthold R, Stevens GA, Riley LM & Bull FC (2018) Worldwide trends in insufficient physical activity from 2001 to 2016: a pooled analysis of 358 population‐based surveys with 1·9 million participants. Lancet Glob Health 6, e1077–e1086.
    1. NCD Risk Factor Collaboration (NCD‐RisC) (2017) Worldwide trends in body‐mass index, underweight, overweight, and obesity from 1975 to 2016: a pooled analysis of 2416 population‐based measurement studies in 128·9 million children, adolescents, and adults. Lancet 390, 2627–2642.
    1. 2018 Physical Activity Guidelines Advisory Committee (2018) 2018 Physical Activity Guidelines Advisory Committee Scientific Report. Department of Health and Human Services, Washington, DC.
    1. World Cancer Research Fund/American Institute for Cancer Research (2018) Continuous Update Project Expert Report 2018. Diet, Nutrition, Physical Activity and Cancer: A Global Perspective. Retrieved June 1, 2020, from
    1. McTiernan A, Friedenreich CM, Katzmarzyk PT, Powell KE, Macko R, Buchner D, Pescatello LS, Bloodgood B, Tennant B, Vaux‐Bjerke A et al. (2019) Physical activity in cancer prevention and survival: a systematic review. Med Sci Sports Exerc 51, 1252–1261.
    1. Tremblay MS, Aubert S, Barnes JD, Saunders TJ, Carson V, Latimer‐Cheung AE, Chastin SFM, Altenburg TM, Chinapaw MJM & on behalf of SBRN Terminology Consensus Project Participants (2017) Sedentary Behavior Research Network (SBRN) – Terminology Consensus Project process and outcome. Int J Behav Nutr Phys Act 14, 75.
    1. Jochem C, Wallmann‐Sperlich B & Leitzmann MF (2019) The influence of sedentary behavior on cancer risk: epidemiologic evidence and potential molecular mechanisms. Curr Nutr Rep 8, 167–174.
    1. American Institute for Cancer Research (2020) Make time + break time. Retrieved June 5, 2020, from
    1. Katzmarzyk PT, Powell KE, Jakicic JM, Troiano RP, Piercy K, Tennant B & 2018 Physical Activity Guidelines Advisory Committee (2018) Sedentary behavior and health: update from the Physical Activity Guidelines Advisory Committee. Med Sci Sports Exerc 51, 1227–1241.
    1. Kerr J, Anderson C & Lippman SM (2017) Physical activity, sedentary behaviour, diet, and cancer: an update and emerging new evidence. Lancet Oncol 18, e457–e471.
    1. Matthews CE, Chen KY, Freedson PS, Buchowski MS, Beech BM, Pate RR & Troiano RP (2008) Amount of time spent in sedentary behaviors in the United States, 2003–2004. Am J Epidemiol 167, 875–881.
    1. World Health Organization (2020) Obesity and overweight fact sheet. Retrieved June 2, 2020, from
    1. Ligibel JA, Alfano CM, Courneya KS, Demark‐Wahnefried W, Burger RA, Chlebowski RT, Fabian CJ, Gucalp A, Hershman DL, Hudson MM et al. (2014) American Society of Clinical Oncology Position Statement on obesity and cancer. J Clin Oncol 32, 3568–3574.
    1. Lauby‐Secretan B, Scoccianti C, Loomis D, Grosse Y, Bianchini F & Straif K (2016) Body fatness and cancer – viewpoint of the IARC Working Group. N Engl J Med 375, 794–798.
    1. Avgerinos KI, Spyrou N, Mantzoros CS & Dalamaga M (2019) Obesity and cancer risk: emerging biological mechanisms and perspectives. Metab Clin Exp 92, 121–135.
    1. Birks S, Peeters A, Backholer K, O'Brien P & Brown W (2012) A systematic review of the impact of weight loss on cancer incidence and mortality. Obes Rev 13, 868–891.
    1. Sumithran P & Proietto J (2013) The defence of body weight: a physiological basis for weight regain after weight loss. Clin Sci 124, 231–241.
    1. Snel M, Jonker JT, Schoones J, Lamb H, de Roos A, Pijl H, Smit JWA, Meinders AE & Jazet IM (2012) Ectopic fat and insulin resistance: pathophysiology and effect of diet and lifestyle interventions. Int J Endocrinol 2012, 983814.
    1. Schmidt S, Monk JM, Robinson LE & Mourtzakis M (2015) The integrative role of leptin, oestrogen and the insulin family in obesity‐associated breast cancer: potential effects of exercise. Obes Rev 16, 473–487.
    1. Thomas RJ, Kenfield SA & Jimenez A (2017) Exercise‐induced biochemical changes and their potential influence on cancer: a scientific review. Br J Sports Med 51, 640–644.
    1. Mason C, Xiao L, Duggan C, Imayama I, Foster‐Schubert KE, Kong A, Campbell KL, Wang C‐Y, Alfano CM, Blackburn GL et al. (2013) Effects of dietary weight loss and exercise on insulin‐like growth factor‐I and insulin‐like growth factor‐binding protein‐3 in postmenopausal women: a randomized controlled trial. Cancer Epidemiol Biomarkers Prev 22, 1457–1463.
    1. Hadgraft NT, Winkler E, Climie RE, Grace MS, Romero L, Owen N, Dunstan D, Healy G & Dempsey PC (2020) Effects of sedentary behaviour interventions on biomarkers of cardiometabolic risk in adults: systematic review with meta‐analyses. Br J Sports Med. 10.1136/bjsports-2019-101154
    1. Booth A, Magnuson A, Fouts J & Foster M (2015) Adipose tissue, obesity and adipokines: role in cancer promotion. Horm Mol Biol Clin Investig 21, 57–74.
    1. Zhao Y, He X, Shi X, Huang C, Liu J, Zhou S & Heng C‐K (2010) Association between serum amyloid A and obesity: a meta‐analysis and systematic review. Inflamm Res 59, 323–334.
    1. de Boer MC, Wörner EA, Verlaan D & van Leeuwen PAM (2017) The mechanisms and effects of physical activity on breast cancer. Clin Breast Cancer 17, 272–278.
    1. Carter S, Hartman Y, Holder S, Thijssen DH & Hopkins ND (2017) Sedentary behavior and cardiovascular disease risk: mediating mechanisms. Exerc Sport Sci Rev 45, 80–86.
    1. Ennour‐Idrissi K, Maunsell E & Diorio C (2015) Effect of physical activity on sex hormones in women: a systematic review and meta‐analysis of randomized controlled trials. Breast Cancer Res 17, 139.
    1. de Roon M, May AM, McTiernan A, Scholten RJPM, Peeters PHM, Friedenreich CM & Monninkhof EM (2018) Effect of exercise and/or reduced calorie dietary interventions on breast cancer‐related endogenous sex hormones in healthy postmenopausal women. Breast Cancer Res 20, 81.
    1. Chandrasekar T, Yang JC, Gao AC & Evans CP (2015) Mechanisms of resistance in castration‐resistant prostate cancer (CRPC). Transl Androl Urol 4, 365–380.
    1. Boyle P, Koechlin A, Bota M, d'Onofrio A, Zaridze DG, Perrin P, Fitzpatrick J, Burnett AL & Boniol M (2016) Endogenous and exogenous testosterone and the risk of prostate cancer and increased prostate‐specific antigen (PSA) level: a meta‐analysis. BJU Int 118, 731–741.
    1. Dimitrakakis C (2011) Androgens and breast cancer in men and women. Endocrinol Metab Clin North Am 40, 533–547, viii.
    1. Pasquali R & Oriolo C (2019) Obesity and androgens in women. Front Horm Res 53, 120–134.
    1. de Sousa CV, Sales MM, Rosa TS, Lewis JE, de Andrade RV & Simões HG (2017) The antioxidant effect of exercise: a systematic review and meta‐analysis. Sports Med 47, 277–293.
    1. Marseglia L, Manti S, D'Angelo G, Nicotera A, Parisi E, Di Rosa G, Gitto E & Arrigo T (2014) Oxidative stress in obesity: a critical component in human diseases. Int J Mol Sci 16, 378–400.
    1. Nieman DC & Wentz LM (2019) The compelling link between physical activity and the body's defense system. J Sport Health Sci 8, 201–217.
    1. Neilson HK, Conroy SM & Friedenreich CM (2014) The influence of energetic factors on biomarkers of postmenopausal breast cancer risk. Curr Nutr Rep 3, 22–34.
    1. El Gendy K, Malcomson FC, Bradburn DM & Mathers JC (2020) Effects of bariatric surgery on DNA methylation in adults: a systematic review and meta‐analysis. Surg Obes Relat Dis 16, 128–136.
    1. El Gendy K, Malcomson FC, Lara JG, Bradburn DM & Mathers JC (2018) Effects of dietary interventions on DNA methylation in adult humans: systematic review and meta‐analysis. Br J Nutr 120, 961–976.
    1. Crovesy L, Masterson D & Rosado EL (2020) Profile of the gut microbiota of adults with obesity: a systematic review. Eur J Clin Nutr. 10.1038/s41430-020-0607-6
    1. Gethings‐Behncke C, Coleman HG, Jordao HWT, Longley DB, Crawford N, Murray LJ & Kunzmann AT (2020) Fusobacterium nucleatum in the colorectum and its association with cancer risk and survival: a systematic review and meta‐analysis. Cancer Epidemiol Biomarkers Prev 29, 539–548.
    1. Guerrero S, López‐Cortés A, Indacochea A, García‐Cárdenas JM, Zambrano AK, Cabrera‐Andrade A, Guevara‐Ramírez P, González DA, Leone PE & Paz‐y‐Miño C (2018) Analysis of racial/ethnic representation in select basic and applied cancer research studies. Sci Rep 8, 13978.
    1. Ibraheem A & Polite B (2017) Improving the accrual of racial and ethnic minority patients in clinical trials: time to raise the stakes. Cancer 123, 4752–4756.
    1. Friedenreich CM, Neilson HK, O'Reilly R, Duha A, Yasui Y, Morielli AR, Adams SC & Courneya KS (2015) Effects of a high vs moderate volume of aerobic exercise on adiposity outcomes in postmenopausal women: a randomized clinical trial. JAMA Oncol 1, 766–776.
    1. Friedenreich CM, O'Reilly R, Shaw E, Stanczyk FZ, Yasui Y, Brenner DR & Courneya KS (2016) Inflammatory marker changes in postmenopausal women after a year‐long exercise intervention comparing high versus moderate volumes. Cancer Prev Res (Phila) 9, 196–203.
    1. GBD 2015 Obesity Collaborators , Afshin A, Forouzanfar MH, Reitsma MB, Sur P, Estep K, Lee A, Marczak L, Mokdad AH, Moradi‐Lakeh M et al. (2017) Health effects of overweight and obesity in 195 countries over 25 years. N Engl J Med 377, 13–27.

Source: PubMed

Sponsors and Collaborators

Medical Conditions

Drug Interventions

3
Subscribe