Physical activity's effect on cancer mortality

Exercise may lower the risk of breast, colon, lung, and prostate cancers.
Exercise may lower the risk of breast, colon, lung, and prostate cancers.

The health benefits of increasing one's level of physical activity are numerous and well-known. For example, exercise lowers the risks for hypertension, stroke, type 2 diabetes, coronary artery disease,1 and several forms of cancer, including breast and colon cancers.2,3 In addition, it is very likely that the risks for prostate, lung, and endometrial cancers are also affected.4,5 Recent research seems to indicate that exercise not only helps to stave off the development of cancer but also may contribute to reducing the risk for death from cancer. 

The Centers for Disease Control (CDC), American College of Sports Medicine (ACSM), and American Heart Association (AHA) recommend that everyone expend 9 metabolic equivalent (MET)–hours of energy per week to take advantage of the health benefits of exercise.6 The MET is a unit of measurement used to express the amount of energy one expends while sitting at rest. The greater the amount of physical activity in which one engages, by increasing either the duration or the intensity of the activity, the higher the number of METs expended. The nationally recognized figure of 9 MET-hours per week is equivalent to 150 minutes of moderate-intensity exercise or 75 minutes of vigorous-intensity exercise per week. Brisk walking is an example of moderate-intensity exercise, and running is an example of high-intensity exercise.

Several prospective studies have shown that the amount of physical activity in which individuals engage, both before and after specific types of cancer are diagnosed, has an effect on their mortality.2-4 These population-based studies had the advantage of being able to recruit large samples and follow the subjects for long periods of time. The greatest risk reductions were demonstrated in breast and colon cancers;2,3 however, the same principles may very well also extend to other forms of cancer.5 

Evidence

In a 2013 study, after an 11-year follow-up, women who had expended more than 7.5 MET-hours of energy per week prior to their breast cancer diagnosis had a risk for dying of their cancer that was 41.5% lower than the risk of women who expended less than that amount of energy.7 A similar trend was seen in men with colorectal cancer, in whom regular exercise before their diagnosis was associated with a 12% reduction in mortality after 5.5 years; in addition, the chance of death from cancer in those with stage II or III tumors at diagnosis was decreased by 50% if they had previously routinely participated in physical activity.8 

Current research indicates that this inverse relationship between exercise and risk for death from specific types of cancer also extends to the period after diagnosis.3,4,9 Three studies conducted between 2005 and 2014 found that women with breast cancer who maintained a level of physical activity at or above the recommendation of 9 MET-hours per week established by the CDC, ACSM, and AHA had a 26% to 67% lower risk for dying from their cancer.2,9,10 

In patients with stage III colorectal cancer, researchers observed lower rates of cancer recurrence and death following treatment if the patients engaged in at least 18 MET-hours of exercise per week.3 A similar correlation may exist in prostate cancer; a 35% reduced risk for mortality from prostate cancer was observed in men who exercised for more than 9 MET-hours per week after their diagnosis.4 

The manner in which exercise habits change after a diagnosis of breast cancer can also affect prognosis. In one study with a 6-year follow-up, women who maintained or exceeded a level of physical activity of 3 MET-hours per week had a survival rate higher than that of women who remained inactive; this was noted even if the women had been physically inactive before their diagnosis.11 Irwin et al reported that women who decreased their exercise time after a diagnosis of breast cancer were 4 times more likely to die of their cancer than those who maintained or increased their level of physical activity.9 Alternatively, women who increased their activity levels reduced their risk for death by 45%.9 

Biological mechanisms 

The precise relationship among exercise, the development of cancer, and death is poorly understood. However, 2 biological mechanisms have been suggested as possible contributors to the protective benefits of physical activity; these physiologic mechanisms involve the family of insulin-like growth factors (IGFs) (Figure 1) and the p53 protein (Figure 2).12,13


Figure 1. Insulin-like growth factor I. 


Figure 2. A schematic of the known protein domains in p53. NLS, nuclear localization signal. Click to enlarge.

IGF-1, IGF-2, and the IGF binding proteins (IGFBP-1 through IGFBP-6) are proteins that play a role in cell division.12 IGF-1 has a stimulating effect on cell proliferation, accelerating the advancement of the cell cycle; in addition, IGF-1 has an inhibitory effect on programmed cell death, or apoptosis.12 In patients with cancer, IGF levels tend to be abnormally high. These proteins have been found to overstimulate cell proliferation in various cancer cell lines, including breast, colorectal, prostate, brain, and uterine cancer cell lines, among several others.12 

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