Mechanisms linking physical activity with cancer

Key Points

  • Regular moderate-intensity or greater physical activity is associated with a reduced risk of several types of cancer, including cancers of the breast, colon and endometrium. For several cancers, engaging in longer exercise sessions, or exercising with greater intensity or for more years, produces greater reductions in cancer risk.

  • Recent findings indicate that women with a history of breast cancer who engage in more than 9 metabolic equivalent (MET)·h/week of recreational physical activity after breast cancer diagnosis, which corresponds to approximately 2–3 h/week of brisk walking, had a significantly lower risk of death or breast cancer recurrence than women who were inactive. Similarly, men or women who are active after a diagnosis of colon cancer appear to have improved prognosis compared with sedentary individuals.

  • Physical activity effects on menstrual function and sex hormones might explain a link between increased physical activity and reduced risk for breast and endometrial cancers. Athletes and physically active premenopausal women have delayed onset of menses, fewer ovulatory cycles and lower circulating levels of oestrogen and progesterone, all factors that are related to breast or endometrial cancer risk.

  • Studies in postmenopausal women indicate that physical activity might affect postmenopausal breast cancer and endometrial cancer risk by reducing body fat, thereby lowering circulating levels of oestrogens and androgens.

  • Insulin resistance, hyperinsulinaemia, hyperglycaemia and type 2 diabetes have been linked to increased risk of breast, colon, pancreas and endometrial cancers. Physical activity improves insulin resistance, reduces hyperinsulinaemia and reduces risk for diabetes, which could explain the link between increased physical activity and reduced risk for these cancers.

  • Increased levels of pro-inflammatory factors and decreased levels of anti-inflammatory factors have been linked with increased cancer risk. Physical activity might reduce systemic inflammation alone or in combination with reduction in body weight or composition through reducing inflammatory cytokines in adipose tissue.

  • Support for an effect of physical activity on the cancer process comes from smaller randomized clinical trials. If definitive evidence from larger clinical trials is obtained to show that increased physical activity can prevent certain cancers, or can improve prognosis, it would be an excellent public-health intervention for reducing the impact of cancer at relatively low cost and risk.


About 25% of cancer cases globally are due to excess weight and a sedentary lifestyle. Physical activity may decrease risk for various cancers by several mechanisms, including decreasing sex hormones, metabolic hormones and inflammation, and improving immune function. The level of physical activity might also be associated with prognosis among individuals with cancer. Randomized clinical trials have shown that physical activity interventions can change biomarkers of cancer risk. Observational studies can also provide useful information on mechanisms that might link physical activity to cancer.

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Figure 1: Hypothesized mechanisms linking physical activity to cancer risk or prognosis.
Figure 2
Figure 3: Hormone changes by change in body fat with physical activity in sedentary or overweight postmenopausal women (aged 50–75 years).


  1. 1

    Vainio, H. & Bianchin, I. F. in International Agency for Research on Cancer Handbooks of Cancer Prevention 249–250 (International Agency for Research on Cancer, Lyon, 2002).

    Google Scholar 

  2. 2

    Thune, I. & Furberg, A. S. Physical activity and cancer risk: dose–response and cancer, all sites and site-specific. Med. Sci. Sports Exerc. 33, S530–S550 (2001).

    CAS  Article  Google Scholar 

  3. 3

    Friedenreich, C. M. & Orenstein, M. R. Physical activity and cancer prevention: etiologic evidence and biological mechanisms. J. Nutr. 132, 3456S–3464S (2002).

    CAS  Article  Google Scholar 

  4. 4

    Bernstein, L. et al. Lifetime recreational exercise activity and breast cancer risk among black women and white women. J. Natl Cancer Inst. 97, 1671–1679 (2005).

    Article  Google Scholar 

  5. 5

    Dallal, C. M. et al. Long-term recreational physical activity and risk of invasive and in situ breast cancer: the California teachers study. Arch. Intern. Med. 167, 408–415 (2007).

    Article  Google Scholar 

  6. 6

    McTiernan, A. et al. Recreational physical activity and the risk of breast cancer in postmenopausal women: the Women's Health Initiative Cohort Study. JAMA 290, 1331–1336 (2003).

    CAS  Article  Google Scholar 

  7. 7

    Holmes, M. D., Chen, W. Y., Feskanich, D., Kroenke, C. H. & Colditz, G. A. Physical activity and survival after breast cancer diagnosis. JAMA 293, 2479–2486 (2005).

    CAS  Article  Google Scholar 

  8. 8

    Pierce, J. P. et al. Greater survival after breast cancer in physically active women with high vegetable-fruit intake regardless of obesity. J. Clin. Oncol. 25, 2345–2351 (2007).

    Article  Google Scholar 

  9. 9

    Meyerhardt, J. A. et al. Impact of physical activity on cancer recurrence and survival in patients with stage III colon cancer: findings from CALGB 89803. J. Clin. Oncol. 24, 3535–3541 (2006).

    Article  Google Scholar 

  10. 10

    Meyerhardt, J. A. et al. Physical activity and survival after colorectal cancer diagnosis. J. Clin. Oncol. 24, 3527–3534 (2006).

    Article  Google Scholar 

  11. 11

    McTiernan, A. Physical activity after cancer: physiologic outcomes. Cancer Invest. 22, 68–81 (2004).

    Article  Google Scholar 

  12. 12

    Frank, L. L. et al. Effects of exercise on metabolic risk variables in overweight postmenopausal women: a randomized clinical trial. Obes. Res. 13, 615–625 (2005).

    Article  Google Scholar 

  13. 13

    McTiernan, A., Ulrich, C., Slate, S. & Potter, J. Physical activity and cancer etiology: associations and mechanisms. Cancer Causes Control 9, 487–509 (1998).

    CAS  Article  Google Scholar 

  14. 14

    Martinez, M. E. et al. Physical activity, body mass index, and prostaglandin E2 levels in rectal mucose. J. Natl Cancer Inst. 91, 950–951 (1999).

    CAS  Article  Google Scholar 

  15. 15

    Meijer, E. P., Goris, A. H., van Dongen, J. L., Bast, A. & Westerterp, K. R. Exercise-induced oxidative stress in older adults as a function of habitual activity level. J. Am. Geriatr. Soc. 50, 349–353 (2002).

    Article  Google Scholar 

  16. 16

    Endogenous Hormones and Breast Cancer Collaborative Group. Endogenous sex hormones and breast cancer in postmenopausal women: reanalysis of nine prospective studies. J. Natl Cancer Inst. 94, 606–616 (2002).

  17. 17

    Kaaks, R., Lukanova, A. and Kurzer, M. S. Obesity, endogenous hormones and endometrial cancer risk: a synthetic review. Cancer Epidemiol. Biomarkers Prev. 11, 1531–1543 (2002).

    CAS  PubMed  Google Scholar 

  18. 18

    Tammela, T. Endocrine treatment of prostate cancer. J. Steroid Biochem. Mol. Biol. 92, 287–295 (2004).

    CAS  Article  Google Scholar 

  19. 19

    Thompson, I. M. et al. The influence of finasteride on the development of prostate cancer. N. Engl. J. Med. 349, 215–224 (2003).

    CAS  Article  Google Scholar 

  20. 20

    Loucks, A. B. Energy availability, not body fatness, regulates reproductive function in women. Exerc. Sport Sci. Rev. 31, 144–148 (2003).

    Article  Google Scholar 

  21. 21

    Loucks, A. B. & Redman, L. M. The effect of stress on menstrual function. Trends Endocrinol. Metab. 15, 466–471 (2004).

    CAS  Article  Google Scholar 

  22. 22

    Williams, N. I., Helmreich, D. L., Parfitt, D. B., Caston-Balderrama, A. & Cameron, J. L. Evidence for a causal role of low energy availability in the induction of menstrual cycle disturbances during strenuous exercise training. J. Clin. Endocrinol. Metab. 86, 5184–5193 (2001).

    CAS  Article  Google Scholar 

  23. 23

    Bonen, A. Recreational exercise does not impair menstrual cycles: a prospective study. Int. J. Sports Med. 13, 110–120 (1992).

    CAS  Article  Google Scholar 

  24. 24

    Rogol, A. D. et al. Durability of the reproductive axis in eumenorrheic women during 1 yr of endurance training. J. Appl. Physiol. 72, 1571–1580 (1992).

    CAS  Article  Google Scholar 

  25. 25

    Bullen, B. A. et al. Endurance training effects on plasma hormonal responsiveness and sex hormone excretion. J. Appl. Physiol. 56, 1453–1463 (1984).

    CAS  Article  Google Scholar 

  26. 26

    Keizer, H. A. et al. Effect of a 3-month endurance training program on metabolic and multiple hormonal responses to exercise. Int. J. Sports Med. 8 (Suppl. 3), 154–160 (1987).

    Article  Google Scholar 

  27. 27

    Bullen, B. A. et al. Induction of menstrual disorders by strenuous exercise in untrained women. N. Engl. J. Med. 312, 1349–1353 (1985).

    CAS  Article  Google Scholar 

  28. 28

    Chan, M. F. et al. Usual physical activity and endogenous sex hormones in postmenopausal women: the European prospective investigation into cancer — Norfolk population study. Cancer Epidemiol. Biomarkers Prev. 16, 900–905 (2007).

    CAS  Article  Google Scholar 

  29. 29

    McTiernan, A. et al. Relation of BMI and physical activity to sex hormones in postmenopausal women. Obesity (Silver Spring) 14, 1662–1677 (2006).

    CAS  Article  Google Scholar 

  30. 30

    Verkasalo, P. K., Thomas, H. V., Appleby, P. N., Davey, G. K. & Key, T. J. Circulating levels of sex hormones and their relation to risk factors for breast cancer: a cross-sectional study in 1092 pre- and postmenopausal women (United Kingdom). Cancer Causes Control 12, 47–59 (2001).

    CAS  Article  Google Scholar 

  31. 31

    McTiernan, A. et al. Effect of exercise on serum estrogen in postmenopausal women: a 12-month randomized controlled trial. Cancer Res. 64, 2923–2928. (2004).

    CAS  Article  Google Scholar 

  32. 32

    McTiernan, A. et al. Effect of exercise on serum androgens in postmenopausal women: a 12-month randomized clinical trial. Cancer Epidemiol. Biomarkers Prev. 13, 1–7 (2004).

    Google Scholar 

  33. 33

    De Souza, M. J. & Miller, B. E. The effect of endurance training on reproductive function in male runners. A 'volume threshold' hypothesis. Sports Med. 23, 357–374 (1997).

    CAS  Article  Google Scholar 

  34. 34

    Abate, N., Haffner, S. M., Garg, A., Peshock, R. M. & Grundy, S. M. Sex steroid hormones, upper body obesity, and insulin resistance. J. Clin. Endocrinol. Metab. 87, 4522–4527 (2002).

    CAS  Article  Google Scholar 

  35. 35

    Hawkins, V. N. et al. Effect of exercise on serum sex hormones in men: a 12-month randomized clinical trial. Med. Sci. Sports Exerc. 40, 223–233 (2008).

    CAS  Article  Google Scholar 

  36. 36

    Kjellman, A., Akre, O., Norming, U., Tornblom, M. & Gustafsson, O. Dihydrotestosterone levels and survival in screening-detected prostate cancer: a 15-yr follow-up study. Eur. Urol. 53, 106–111 (2007).

    Article  Google Scholar 

  37. 37

    Nishiyama, T., Ikarashi, T., Hashimoto, Y., Suzuki, K. & Takahashi, K. Association between the dihydrotestosterone level in the prostate and prostate cancer aggressiveness using the Gleason score. J. Urol. 176, 1387–1391 (2006).

    CAS  Article  Google Scholar 

  38. 38

    Kaaks, R. & Lukanova, A. Energy balance and cancer: the role of insulin and insulin-like growth factor-I. Proc. Nutr. Soc. 60, 91–106 (2001).

    CAS  Article  Google Scholar 

  39. 39

    Wolf, I., Sadetzki, S., Catane, R., Karasik, A. & Kaufman, B. Diabetes mellitus and breast cancer. Lancet Oncol. 6, 103–111 (2005).

    CAS  Article  Google Scholar 

  40. 40

    Boule, N. G., Haddad, E., Kenny, G. P., Wells, G. A. & Sigal, R. J. Effects of exercise on glycemic control and body mass in type 2 diabetes mellitus: a meta-analysis of controlled clinical trials. JAMA 286, 1218–1227 (2001).

    CAS  Article  Google Scholar 

  41. 41

    Ross, R. et al. Reduction in obesity and related comorbid conditions after diet-induced weight loss or exercise-induced weight loss in men: a randomized, controlled trial. Ann. Intern. Med. 133, 92–103 (2000).

    CAS  Article  Google Scholar 

  42. 42

    Ross, R. et al. Exercise-induced reduction in obesity and insulin resistance in women: a randomized controlled trial. Obes Res. 12, 789–798 (2004).

    Article  Google Scholar 

  43. 43

    Duncan, G. E. et al. Exercise training, without weight loss, increases insulin sensitivity and postheparin plasma lipase activity in previously sedentary adults. Diabetes Care 26, 557–562 (2003).

    CAS  Article  Google Scholar 

  44. 44

    Campbell, K. L. & McTiernan, A. Exercise and biomarkers for cancer prevention studies. J. Nutr. 137, 161S–9S (2007).

    CAS  Article  Google Scholar 

  45. 45

    Weiss, E. P. et al. Improvements in glucose tolerance and insulin action induced by increasing energy expenditure or decreasing energy intake: a randomized controlled trial. Am. J. Clin. Nutr. 84, 1033–1042 (2006).

    CAS  Article  Google Scholar 

  46. 46

    McTiernan, A. et al. No effect of exercise on insulin-like growth factor 1 and insulin-like growth factor binding protein 3 in postmenopausal women: a 12-month randomized clinical trial. Cancer Epidemiol. Biomarkers Prev. 14, 1020–1021 (2005).

    CAS  Article  Google Scholar 

  47. 47

    Orenstein, M. R. & Friedenreich, C. Insulin-like growth factors and exercise: review of the evidence. J. Phys. Act. Health 1, 291–320 (2004).

    Article  Google Scholar 

  48. 48

    Il'yasova, D. et al. Circulating levels of inflammatory markers and cancer risk in the health aging and body composition cohort. Cancer Epidemiol. Biomarkers Prev. 14, 2413–2418 (2005).

    CAS  Article  Google Scholar 

  49. 49

    Wetmore, C. M. & Ulrich, C. M. in Cancer Prevention and Management through Exercise and Weight Control (ed. McTiernan, A.) 157–175 (CRC Taylor Francis, Boca Raton, 2006).

    Google Scholar 

  50. 50

    Esposito, K. et al. Effect of weight loss and lifestyle changes on vascular inflammatory markers in obese women: a randomized trial. JAMA 289, 1799–1804 (2003).

    CAS  Article  Google Scholar 

  51. 51

    Jakobisiak, M., Lasek, W. & Golab, J. Natural mechanisms protecting against cancer. Immunol. Lett. 90, 103–122 (2003).

    CAS  Article  Google Scholar 

  52. 52

    Nieman, D. C. Exercise immunology: practical applications. Int. J. Sports Med. 18 (Suppl. 1), S91–S100 (1997).

    CAS  Article  Google Scholar 

  53. 53

    Ainsworth, B. E., Sternfeld, B., Slattery, M. L., Daguise, V. & Zahm, S. H. Physical activity and breast cancer: evaluation of physical activity assessment methods. Cancer 83, 611–620 (1998).

    CAS  Article  Google Scholar 

  54. 54

    Irwin, M. L. & Ainsworth, B. E. Physical activity interventions following cancer diagnosis: methodologic challenges to delivery and assessment. Cancer Invest. 22, 30–50 (2004).

    Article  Google Scholar 

  55. 55

    U. S. Department of Health and Human Services. Physical activity and health: a report of the Surgeon General (U. S. Department of Health and Human Services, Centers for Disease Control and Prevention, National Center for Chronic Disease Prevention and Health Promotion, Atlanta, 1996).

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McTiernan, A. Mechanisms linking physical activity with cancer. Nat Rev Cancer 8, 205–211 (2008).

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