Abstract PL03-04: Exercise, adiposity, and cancer

Abstract Introduction: The International Agency for Research on Cancer (IARC) estimates that 25% of cancer cases worldwide are due to overweight/obesity and a sedentary lifestyle.(1) Several observational and intervention studies suggest that the greatest benefit from physical activity is seen in individuals who are normal weight or, in intervention studies, in persons who exercise at high enough levels to lose body fat. This talk will review human data on the associations between exercise, adiposity, and cancer incidence and biomarkers, and provide specific examples from cohort and clinical trial studies. It will also include the conclusions of the U.S. Department of Health and Human Services Physical Activity Guidelines Committee report that reviewed the state of the epidemiologic literature on the associations between physical activity and risk for several cancers. Adiposity: Excess bodyweight, commonly measured as increased body-mass index (BMI, kg/m2), is associated with the risk of several common cancers. Overweight and obesity (BMI ≥ 25 kg/m2) increase risk for several cancers including colon, postmenopausal breast, endometrium, lower esophagus, kidney, liver, and other less common cancers. Results of a recent meta-analysis of cohort studies(2) indicate that for each 5 kg/m2 increase in BMI there are increased risks in the order of 52% for esophageal adenocarcinoma, 33% for thyroid, and 24% for colon and renal cancers in men. For women, the corresponding increased risks were 59% for endometrium and gallbladder, 51% for esophageal adenocarcinoma, and 34% for renal cancers. Positive but weaker associations between BMI were also observed for rectal cancer and malignant melanoma in men, for pancreas, thyroid, and colon in women, and for leukemia, multiple myeloma, and non-Hodgkin lymphoma in both sexes. Observational data suggest that lifetime weight maintenance may be the best strategy for reducing cancer risk.(1, 3, 4) Exercise: Several hundred case-control and cohort studies have studied associations between physical activity and risk of several cancers.(5) The majority of studies support a moderate, inverse relation between physical activity and the development of breast, colon, lung, endometrial, and ovarian cancers cancers.(5) Individuals engaging in aerobic physical activity for approximately 3 to 4 hours per week at moderate or greater levels of intensity have on average a 30% reduction in colon cancer risk and a 20% to 40% lower risk of breast cancer, compared with those who are sedentary. A dose-response relation also is apparent, with risk decreasing at higher levels of physical activity. However, little information is available regarding what additional amounts and intensity of physical activity are associated with additional risk reductions; it also is unclear what the magnitude of the additional decrements in risk may be. The available evidence suggests that at least 30 to 60 minutes per day of moderate-to-vigorous intensity physical activity is required to significantly lower the risk of colon and breast cancer. Some data suggest that both physical activity and normal weight maintenance provides the optimal risk reduction for postmenopausal breast cancer.(6) Compared with sedentary individuals, the available epidemiologic data suggest that active people have approximate reductions in risk of lung, endometrial, and ovarian cancers of 20%, 30%, and 20%, respectively. The data overall do not support associations of physical activity with prostate or rectal cancers. Too few data exist regarding the other site-specific cancers to make reasonable conclusions. Potential Mechanisms Linking Exercise and Adiposity to Cancer: Increased physical activity and maintenance of normal weight may lower cancer risk by several mechanisms including lowering estrogens, testosterone, prolactin, insulin and insulin resistance, and decreasing inflammation.(7) Randomized clinical trial data have found reductions in insulin and inflammation with weight loss and exercise,(5, 8-10) but few studies have assessed exercise or weight loss effects on cancer-specific biomarkers such as sex hormones or target tissue proliferation or apoptosis markers. Two randomized clinical trials have shown that 12-months physical activity interventions (225 minutes/week of moderate-to-vigorous activity) decrease serum estrogens particularly in postmenopausal women who reduce body fat.(11, 12) Trials in younger women show exercise-induced reductions in estrogens if energy intake is not increased to compensate for energy expenditure.(7) One trial found reduced colon cell proliferation in men, but not women, randomized to 12-months aerobic exercise (360 minutes/week of moderate-to-vigorous activity) vs. control.(13) A trial is ongoing testing effects of 12-months weight loss and exercise interventions on cancer biomarkers in 438 overweight/obese postmenopausal women, including sex hormones, insulin and insulin resistance, and inflammation. Women were randomized to: caloric restriction with 10% weight loss goal (N=118), aerobic exercise, 225 minutes/week (N=117), both caloric restriction + exercise (N=116), or control (N=87). Preliminary analyses show statistically significant reductions in estrone and estradiol in either caloric restriction group compared with controls. Women in the weight loss interventions also significantly reduced inflammation markers. Updated results will be presented. Summary: Available evidence suggests that overweight and obesity increase risk for several cancers, that lifelong weight maintenance decreases risk, and that physical activity reduces risk for several cancers. Determining the independent and combined effects of physical activity and normal weight maintenance can be approached through animal models, human intervention studies, and epidemiologic observational studies. Optimal evidence relevant to humans may come from randomized trials testing interventions specifically designed to produce weight loss, exercise, or both. Effects of other means of weight loss, such as bariatric surgery and medications, on cancer biomarkers are not known. References: 1. IARC Working Group on Evaluation of Cancer-Preventive Strategies: Weight Control and Physical Activity. Lyon: IARC Press; 2002. 2. Renehan AG TM, Egger M, Heller RF, Zwahlen M. Body-mass index and incidence of cancer: a systematic review and meta-analysis of prospective observational studies. Lancet 2008;371(9612):569-78. 3. Morimoto LM, White E, Chen Z, et al. Obesity, body size, and risk of postmenopausal breast cancer: the Women's Health Initiative (United States). Cancer Causes Control 2002;13(8):741-51. 4. Eliassen AH, Colditz GA, Rosner B, Willett WC, Hankinson SE. Adult weight change and risk of postmenopausal breast cancer. Jama 2006;296(2):193-201. 5. Physical Activity Guidelines Advisory Committee. Physical Activity Guidelines Advisory Committee Report, 2008. Washington, DC: U.S. Department of Health and Human Services, 2008. 6. McTiernan A, Kooperberg C, White E, et al. Recreational physical activity and the risk of breast cancer in postmenopausal women: the Women's Health Initiative Cohort Study. JAMA 2003;290(10):1331-6. 7. McTiernan A. Mechanisms linking physical activity with cancer. Nat Rev Cancer 2008;8(3):205-11. 8. Haffner S, Temprosa M, Crandall J, et al. Intensive lifestyle intervention or metformin on inflammation and coagulation in participants with impaired glucose tolerance. Diabetes 2005;54(5):1566-72. 9. Reduction in the incidence of type 2 diabetes with lifestyle intervention or Metformin. Diabetes Prevention Program Research Group. N Engl J Med 2002;346:393-403. 10. Campbell PT, Campbell KL, Wener MH, et al.A yearlong exercise intervention decreases CRP among obese postmenopausal women. Med Sci Sports Exerc 2009;41(8):1533-9. 11. Friedenreich CM, Woolcott CG, McTiernan A, et al. Alberta physical activity and breast cancer prevention trial: sex hormone changes in a year-long exercise intervention among postmenopausal women. J Clin Oncol;28(9):1458-66. 12. McTiernan A,Tworoger S, Schwartz RS, et al. Effect of Exercise on Serum Estrogen in Postmenopausal Women: a 12-Month Randomized Controlled Trial. Cancer Research 2004;64(8):2923-8. 13. McTiernan A, Yasui Y, Sorensen B, et al. Effect of a 12-month exercise intervention on patterns of cellular proliferation in colonic crypts: a randomized controlled trial. Cancer Epidemiol Biomarkers Prev 2006;15(9):1588-97. Citation Information: Cancer Prev Res 2010;3(12 Suppl):PL03-04.

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