Thursday, March 16, 2006

The effect of physical activity on the incidence and progression of malignant tumours

In the 1990’s, cancer was the #1 cause of potential years of life lost among North Americans. With the exception of nonmelanoma skin cancer, breast cancer is the most commonly diagnosed malignancy in women. Only lung cancer accounts for more female cancer deaths. Approximately 40,800 women died from breast cancer during the year 2000 2. In the USA, colorectal cancer has the third highest incidence rate for both sexes and accounts for 10% of all cancer deaths 6, 7. Pancreatic cancer, although rare, once diagnosed has a poor prognosis in that less than 5% of patients are expected to survive 5 years 23. To date, numerous survey studies have reported a decreased risk of various cancers in individuals who exercise regularly. The most compelling evidence so far has been for breast and colon cancer, but physical activity has been associated with a decreased incidence of ovarian, lung, prostate, and endometrial cancers 13. In light of the enormous impact that cancer has on the population, in both health care costs and individuals’ quality of life, methods of wide-spread prevention of this disease would be of great benefit. The purpose of this article is to explore the effects of exercise on the prevention and progression of cancers.

Physical activity has been found to decrease the incidence and progression of several cancers through mechanisms such as increasing and/or maintaining insulin sensitivity, decreasing body fat, regulating hormones, and enhancing the immune response.

It has been hypothesized that insulin resistance is common among overweight and under active individuals, and may play a role in the development of pancreatic, breast, and colonic cancer 4, 19, 23. People with insulin resistance have a greater concentration of sugar in the blood, which forces the pancreas to secrete more insulin. High blood levels of insulin have been hypothesized to increase cell division in the pancreas, which will result in the proliferation of cancer cells. In another study, cell cultures introduced to high levels of insulin increased the growth of tumour cells 13. It is well established that physical activity decreases levels of insulin in the blood by making insulin more effective at removing sugar from the bloodstream, thereby decreasing the amount of insulin that needs to be synthesized in the pancreas 23. Exercise also decreases colon transport time, protecting the body from prolonged exposure to colonic toxins 17. In this way, exercise would have a preventative effect against cancer. Dr. Thune has illustrated that physical activity is protective against proximal tumours in the colon, but less so against distal tumours, while not at all against rectal cancers 10. Conversely, in a study by Colbert et al, they found that when the colons of mice were exposed to multiple intestinal adenomas, there were fewer total colon polyps in the exercised mice versus the non-exercised mice, however the results were not statistically significant 5. In another study, the risk of colon cancer was increased among men employed in sedentary occupations 1.

It is well known that exercise increases lean body mass. An association between lean body mass and a decreased risk of cancer is well established 1. In 1997, The New England Journal of Medicine reported that the risk of breast cancer was lowest in lean women who exercised at least 4 hours per week 20. Other studies have shown that when compared to a sedentary control group, the women who reported engaging in any strenuous physical activity between the ages of 14-22 had a modest reduction in the risk of breast cancer. Women who reported engaging in vigorous physical activity at least once a day within the same age range had an average 50-60% reduction in the risk of developing breast cancer 3, 15, 22. Strenuous exercise after menarche appears to decrease the risk of post-menopausal breast cancer 12. It has also been reported that women who engage in moderate levels of physical activity have a lower waist-hip ratio, lower BMI (body-mass index), and were less likely to smoke and less likely to have diabetes mellitus 16. This tendency to avoid smoking would indirectly decrease the risk of lung cancer. In another study, even after adjusting for smoking, BMI, and other potential confounders, the protective effect of exercise remained unchanged 1. Yet another study reported a relative risk of breast cancer as 1.00 for a sedentary individual (this was the reference group), 0.81 in moderately active women, and 0.48 in women who exercise regularly 21. This group was also adjusted for age at entry, BMI, height, country of residence, and number of children.

Researchers theorize that physical activity diminishes the chance of developing breast cancer by decreasing the levels of two hormones that have been linked to breast tumour production; estradiol and progesterone. Two ways that physical activity can decrease exposure to these hormones are by suppressing ovulation during adolescence, and by delaying ovulation during the cycle 22. This delay decreases the luteal phase – during which time these hormones are in greatest concentration. Adolescent girls engaging in regular physical activity are more likely not to ovulate, even if they are menstruating, thereby producing less estradiol and progesterone. In one study, female college alumni who actively participated in one or more team sports during college reported less subsequent cancers of the breast, uterus, and ovary than did non-athlete alumni 1. Also, data for cancer of the cervix and endometrium are suggestive of a protective effect for a higher load of exercise.

Another hormone thought to play a large role in cancer prevention is DHEA. DHEA is an adrenal hormone thought to have “anti cancer” and “anti aging” effects 13. A number of researchers have hypothesized that DHEA prevents carcinogenesis and may act as a chemopreventive agent. DHEA levels decrease with hyperinsulinemia (insulin resistance). Hyperinsulinemia has been clearly associated with high blood pressure and obesity. Exercise has been shown to increase DHEA while also increasing insulin sensitivity.

An increased incidence of cancer has been reported among individuals with several different types of immunodeficiencies and among immunosuppressed patients 11. Increased exhaustive exercise has been found to increase cells of the immune system 24, for example natural killer (NK) cells, lymphocytes, and polymorphonuclear neutrophils (PMN). A decrease in NK cell activity has been found in individuals with high familial incidence of cancer, demonstrating a genetic component to cancer. Medium and high levels of lymphocyte activity have been associated with reduced risk of cancers 11. In addition, lymphocyte activity has been positively associated with age and keeping the body weight close to population norm. This shows that an increase in exercise results in an increase of immune cells. This increase in immune cells has been found to have an inverse association with the incidence of cancer. This evidence supports the role of exercise in preventing the development of cancer.

Researchers have also examined the role of physical activity in speeding the recovery process after cancer treatment as well as during treatment. Doctors have found that exercise during chemotherapy or radiation treatment helps to reduce the patients’ level of fatigue 9, 14.
In a study of 25 women, 15 exercising participants were matched against 10 controls. The exercising participants completed a 20-week program consisting of aerobic machine exercise, progressive strength training and specialty exercises. Patients completed a quality of life survey after the 20-week program, and were re-evaluated 2 years later with a survey concerning cancer status, health-care information, exercise status, and alternative health practices. Results after 20 weeks indicated a 45% improvement in strength, a 35% increase in aerobic exercise time, a significant improvement in the metabolic equivalent of the task (MET) capacity, and an average 25% improvement in quality of life indices. After 2 years, a total of 86% of the exercise group continued to train after the program had completed. This group showed a lower frequency of physical therapy referrals, lower out-of-pocket medical expenses, and a high percentage of complementary health usage when compared to the control group. After 2 years there were no reported deaths in the exercise group, while 3 women from the control group had passed away. Two individuals in the control group had episodes of recurrence while the exercise group had none 8.

In summary, it has become apparent that physical activity has been strongly associated with lowering an individual’s risk of developing cancer. The ability of physical activity to influence the factors associated with cancer development may be the key to understanding how it can lower the overall risk of cancer. While the exact mechanism is not known, it is likely that physical activity operates through multiple mechanisms that overlap some of the other known risk factors 18.

1. ALBANES, D., BLAIR, A., TAYLOR, P.R. Physical activity and risk of cancer in the NHANES 1 population. American Journal of Public Health. 79(6): 744-750. 1989.
2. ALBERG, A.J., SINGH, S., MAY, J., HELZSOUER, K. Epidemiology, prevention, and early detection of breast cancer. Current Opinion in Oncology. 12(6): 515-520. 2000.
3. B.L. Exercise and breast cancer. Nutrition Action Health Letter. 25(8): 13-15. 1998.
4. BOUTRON-RAULT, M.C., SENESSE, P., MEANCE, S., BELGHITI, C., FAIVRE, J. Energy intake, body mass index, physical activity, and the colorectal adenoma-carcinoma sequence. Nutrition and Cancer. 39(1); 50-57. 2001.
5. COLBERT, L.H., DAVIS, J.M., ESSIG, D.A., GHAFFAR, A., MAYER, E.P. Exercise and tumor development in a mouse predisposed to multiple intestinal adenomas. Medicine & Science in Sports & Exercise. 32(10): 1704-1708. 2000.
6. COURNEYA, K.S., FRIENDRICH, C.M., ARTHUR, K., BOBICK, T.M. Physical exercise and quality of life in postsurgical colorectal cancer patients. Psychology, Health & Medicine. 4(2): 181-188. 1999.
7. COURNEYA, K.S., HELLSTEN, A.M. Cancer prevention as a source of exercise motivation: An experimental test using protection motivation theory. Psychology, Health & Medicine. 6(1): 59-65. 2001.
8. DURAK, E.P., WOLLITZER, A.O., LILLY, P.C. Preliminary results of exercise with breast cancer patients: A two year follow-up survey. Alternative Therapies in Health & Medicine. 4(2): 102. 1998.
9. EASTERBROOK, K. Exercise for speedy recovery. Canadian Journal of Health & Nutrition. 222: 60-61. 2001.
10. HILL, M.J. International symposium: Way of life and cancer. European Journal of Cancer Prevention. 9(1): 65-68. 2000.
11. IMAI, K., MATSUYAMA, S.M., SUGA, K., NAKACHI, K. Natural cytotoxic activity of peripheral-blood lymphocytes and cancer incidence: an 11-year follow-up study of a general population. The Lancet. 356: 1795-1799. 2000.
12. Life Extension. Lifetime exercise activity and breast cancer risks. 6(2): 81. 2000.
13. MacINTOSH, A. Exercise therapeutics update & commentary: Exercise as a detoxification technique, thereby its effectiveness in the prevention of cancer. Townsend Letter for Doctors & Patients. 202: 26-30. 2000.
14. MILLER, K.E. Can exercise reduce fatigue during chemotherapy? American Family Physician. 60(3): 988-992. 1999.
15. MITTENDORF, R. Physical activity in young women may reduce risk of breast cancer. American Family Physician. 10: 1487. 1995.
16. MOORE, D.B., FOLSOM, A.R., MINK, P.J., HONG, C-P., ANDERSON, K., KUSHI, L.H. Physical activity and incidence of postmenopausal breast cancer. Epidemiology. 11(3): 292-296. 2000.
17. SHEPHARD, R.J. Absolute versus relative intensity of physical activity in a dose-response context. Medicine & Science in Sport & Exercise. 33(6): S400-S418. 2001.
18. SLATTERY, M.L., POTTER, J.D. Physical activity and colon cancer: confounding or interaction? Medicine & Science in Sports & Exercise. 34(6): 913-919. 2002.
19. THUNE, I. Physical exercise in rehabilitation program for cancer patients? The Journal of Alternative and Complementary Medicine. 4(2): 205-207. 1998.
20. THUNE, I., BRENN, R., LUND, E., GAARD, M. Physical activity and the risk of breast cancer. The New England Journal of Medicine. 336(18): 1269-1275. 1997.
21. THUNE, I., LUND, E. Exercise and breast cancer. (Correspondence). The New England Journal of Medicine. 337(10): 708-709. 1997.
22. Tufts University Diet & Nutrition Letter. A breast cancer risk you can do something about. 12(9): 7-10. 1994.
23. Tufts University Health & Nutrition Letter. Pancreatic cancer may be linked to obesity and inactivity. 19(10). 2001.
24. WOODS, J.A., DAVIS, J.M., SMITH, J.A., NIEMAN, D.C. Exercise and cellular innate immune function. Medicine & Science in Sports & Exercise. 31(1); 57-66. 1999.