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Exercise & Cancer

What do you think of when you hear the word "cancer"? Many people visualize a sickly person going through bout after bout of chemotherapy or radiation therapy, and the collateral damage that goes with that. While this may be the case with some aggressive cancers, it's not the "norm." A lot of people with cancer live active, happy lives, and others beat it altogether.

For over a decade, research has repeatedly shown that exercise is a protective factor that can reduce the risk of getting many types of cancer, though until more recently, the exact mechanisms for this prevention were unknown. A paper published in the Journal of the American Medical Association (Moore et al. 2016) revealed that physical activity lowers the risk of 13 types of cancer! (For more on this study, see the sidebar "Exercise and Cancer Prevention.")

There's even more positive news about exercise and cancer. A report from the Memorial Sloan Kettering Cancer Center stated, "Multiple studies show that regular physical activity is linked to increased life expectancy after a diagnosis of cancer, in many cases by decreasing the risk of cancer recurrence" (Grisham 2014). The American Cancer Society, World Cancer Research Fund, American Institute for Cancer Research, American College of Sports Medicine, and U.S. Department of Health and Human Services are just some of the organizations that advocate physical activity for cancer patients and survivors (Grisham 2014). Thus, it is not a question of whether exercise helps, but rather of how much works—based on dosage, quality, conditioning and cancer type.

There are three ways to look at battling cancer. For those who don't have it, lowering risk is the primary goal. For those who've had it, successfully recovering and of course reducing the chances of recurrence are of utmost importance. For those who currently have it, the priorities are getting rid of it and minimizing the harmful effects that both the disease and the treatment have on the body. Exercise has been shown to help with all three.

Cancer and Exercise Research: An Overview

Cancer is simply a collection of abnormal cells that are dividing without stopping; in other words, their growth is out of control. Most often (not always), the result is a tumor. Some tumors are benign and will stay localized, but cancerous tumors are malignant and may spread (metastasize) to other parts of the body.

The immune system houses the forces that keep cancer at bay. In fact, we have a potent inflammatory agent called tumor necrosis factor that can be friend or foe, depending on the situation (Wang & Lin 2008). When our immune system is strong, we battle cancer successfully. When immunity is not strong, or if the cancer is potent, we may lose the battle and develop noticeable symptoms of cancerous growth.

Taking an "active approach" to fighting cancer is indeed the best choice. In a 2005 Harvard study, breast cancer patients who exercised at moderate intensities 3–5 hours per week (high volume) lowered the odds of dying from cancer by about half, compared with sedentary patients (Holmes et al. 2005). Even a little exercise improved patients' odds, regardless of stage or diagnosis timing.

Studies have also shown those who exercise early in life have reduced chances of breast cancer later in life. Chinese women who exercised an average of 70 minutes per week during their teens reduced their chances of dying from cancer by 16%, and those who kept exercising as adults had a 20% lower risk of premature death from all causes, compared with other women (Nechuta et al. 2015).

The amount of exercise to aim for, particularly during or just after dealing with a bout of cancer, is a delicate balance of getting enough to make a difference and not getting too much—an amount that could suppress immune function. The reason for this yin-yang relationship is linked to the endocrine system and the body's perception of exercise as stress.

Epinephrine—released during exercise—helps to circulate natural killer cells in tumors. The NK cells move into the bloodstream and infiltrate tumor cells, causing them to shrink. Researchers confirmed this theory using several different methods, including using mice with no NK cells, blocking epinephrine flow and injecting mice with epinephrine. All studies led to the same conclusion: Epinephrine caused NK cell infiltration (Neiman et al. 1995). Further studies found that it was Interleukin-6 (IL-6), a known inflammatory marker, that served as the immune cell signal. Only IL-6 sensitive NK cells showed this response, and IL-6 helped guide NK cells to the tumors.

Other hormonal effects of exercise include insulin reduction, an increase in insulin-like growth factor 1 (IGF-1) and a decrease in leptin levels (Dutta et al. 2012). When leptin levels are high, various cancers survive better, grow faster and spread more (Dutta et al. 2012). Additionally, leptin causes the release of inflammatory agents that can complicate cancer risk. Sex hormones, cortisol and prostaglandins are currently being researched for their roles in cancer progression and prevention.

Exercise has also been shown to minimize the negative effects of conventional cancer therapy. A meta-analysis of 16 studies found that cancer patients who exercised had consistently better quality of life, compared with their nonexercising counterparts (McTiernan 2006). The benefits were both physical and mental and included less fatigue, more energy, fewer hospital stays and doctor visits, and higher self-esteem.

Epigenetics and Exercise

Some of the mechanisms by which exercise reduces cancer may lie in its very origin—our genes. The field of epigenetics (the study of biological mechanisms that will switch genes on or off) is expanding, as is research about how exercise turns various genes off and on. Exercise has been shown to inhibit inflammatory cytokine production by the ASC gene, which functions as a key mediator in apoptosis (cell death), revealing at least one mechanism of exercise's anti-inflammatory effect (Nakajima et al. 2010).

Many alterations in gene expression occur through methylation—a process by which methyl groups are added to DNA—or demethylation of various DNA sequences. Research has found a relationship between some hypomethylation and many cancer cells (Hoffman & Schultz 2005). Physical activity is associated with higher levels of methylation (Zhang et al. 2011); thus, exercise may restore normal gene function after demethylation has occurred.

Hypermethylation may also be a cancer culprit. One particular tumor-suppressor gene (CACNA2D3) is silenced by hypermethylation. Yuasa et al. (2009) found that CACNA2D3 methylation was more common in inactive people, compared with people who were physically active.This same phenomenon has also been seen with L3MBTL1, another gene that suppresses tumors (Brown 2015).

Coyle et al. (2007) found physical exercise reversed promoter hypermethylation, which silenced a tumor-suppressor cell and lowered estrogen levels (also found to promote certain breast cancer carcinogenesis). Thus, exercise may improve the chances of a cancer patient living, owing to its influence on tumor-suppressor genes, inflammation and hormone levels.

Exercise Types and Intensities

Exercise has been established as a boon for cancer prevention and recovery, but what types of exercise—and how much—are beneficial?

To start, about 500,000 cancer cases each year are attributed to obesity (McTiernan 2006), and exercise may help many people obtain a healthy weight. Studies show that high-intensity
interval training (HIIT) burns more fat and calories and lowers blood sugar levels more effectively than moderate exercise. HIIT training seems to alter the hormonal milieu and lower the amount of estrogen that fat cells produce, thus dampening the risk for estrogen-sensitive cancers. Focusing efforts on a few HIIT sessions a week may put the hit on cancer progression and reduce belly girth as well. A study by Courneya et al. (2013) found that a high dose of aerobic exercise (50–60 minutes) outperformed both standard amounts (25‐30 minutes) and a combination dose of resistance and aerobic exercise (50–60 minutes).

Vigorous exercise also increases blood flow and mitochondria vitality more than moderate exercise. Increased circulation means increased oxygen and more immune cells flowing throughout the body, including the liver. Cancer researchers are still investigating the liver's role, but we know it detoxifies potentially damaging substances (carcinogens), including excess estrogen.

Some longevity theorists focus on mitochondria as key players in keeping genes healthy. Damaged mitochondria may lead to genetic mutations that flip the "on switch" for an oncogene (cancer gene). When mitochondria are "pushed" during aerobic exercise, free radicals are produced. Most people think this a bad thing, and they load up on antioxidant supplements. In reality, the body will respond by upping its own antioxidant production, but it will also stimulate more mitochondria production. [Editor's note: This issue's Research column discusses the potentially negative effects of antioxidant supplementation.]

Another paradigm shift in the anticancer arena concerns the type of exercise that works best to reduce recurrence and mortality. In the past, mild aerobic exercise was emphasized. Now, the emphasis is moving toward higher-intensity exercise, resistance training and a reduction in the time people sit. A 2009 study found that greater muscle strength in men was associated with a 40%–50% lower risk of dying from cancer (Ruiz et al. 2009). Strenuous exercise in women at age 12 was associated with reduced breast cancer during pre- and postmenopause (Lee & Oguma 2006). Even moderate exercise or heavy lifting as part of one's daily life caused a 38% reduction in risk of invasive breast cancers and postmenopausal tumors. Unfortunately, the guidelines on how much and what types of exercise are best if a person has cancer are still vague, and much needs to be considered on an individual case basis.

Specific Areas of Research and Promise

While different cancers share many commonalities, they are also unique in lethality, progression, effective therapies, and response to exercise. Let's look at how exercise affects four common types of cancer: colorectal, breast, lung and prostate.

Colorectal Cancer

Data show that active men and women have about a 30%–40% lower risk of developing colorectal cancer, compared with inactive individuals (Slattery 2004). This is independent of body mass index. Moreover, a dose-dependent relationship exists, with the most active individuals getting the most risk reduction (Ballard-Barbash et al. 2006; McTiernan 2006).

Slattery (2004) did not determine how exercise might help someone already diagnosed with colorectal cancer. It appears the protective effect is greatest with high volume/high intensity. The estimated dosage for colon cancer protection seems to be 30–60 minutes of moderate to vigorous activity per day (Lee & Oguma 2006). In a study on patients with stage 3 colorectal cancer, those who performed physical activity remained cancer-free for 6 months after surgery and chemotherapy. Activity reduced the risk of the cancer returning (Meyerhardt et al. 2006).

Breast Cancer

Breast cancer research is abundant, with over 60 published studies from various continents. With this large body of research comes a wide range of preventive effect, with 20%–80% prevention being reported across all studies (Lee & Oguma 2006; McTiernan 2006). Physically active women have at least a 20%–30% reduction in risk, compared with inactive women. Evidence shows that 30–60 minutes of moderate- to high-intensity physical exercise each day is needed to decrease the risk of breast cancer. Both pre- and postmenopausal exercise is important, with vigorous exercise seeming to be most effective (Lee & Oguma 2006; McTiernan 2006).

Note: Exercise dosages should be individualized based on the particular health, cancer stage, immune status, training history, and tolerance of the individual to movement. The program should be closely monitored (with laboratory measurements taken regularly) and adjusted or even terminated if results are not going in the proper direction.

Trends show high levels of moderate and vigorous physical activity during adolescence may be especially preventive versus exercise later in life (Lee & Oguma 2006; McTiernan 2006).

Researchers believe there is likely a BMI-related effect as well. Women with a normal BMI (18.5–24.9 kg/m2) have the greatest risk reduction with exercise. Scientists theorize that lowering certain hormones, especially in premenopausal women, may help prevent tumor development. IGF-1, which is released during exercise, may not only improve immune status but also help with weight maintenance and fat reduction (McTiernan 2006).

A study by Irwin et al. (2008) looked at the associations between pre- and postdiagnosis physical activity and mortality in women with breast cancer. Across the board, the study found that exercise improved mortality.

Those who expended at least 9 metabolic equivalent hours (MET-hrs) per week, equal to about 2–3 hours of brisk walking, improved mortality by 69% for those active in the year before diagnosis and by 33% for those active 2 years after diagnosis. Women exercising for 2.5 hours per week 2 years after diagnosis had a 67% lower risk of death compared with inactive women. Further, women who increased their physical activity after diagnosis had a 45% lower risk of dying compared with women who remained inactive before and after diagnosis. And the most stunning statistic: Those who decreased their physical activity after diagnosis had a 4 times greater risk of dying. Thus, being active before and after diagnosis improves mortality quite a bit.

Kim, Choi & Jeong (2013) performed a meta-analysis, using data from many past studies, to find out more precisely how physical activity affects breast cancer survivors after diagnosis. Out of 127 studies, 33 satisfied the selection criteria for the analysis. The researchers then categorized people according to MET-hrs/wk.

Results showed a dose-dependent effect of exercise, with those who exercised more than 3 MET-hrs/wk having significantly lower cancer mortality (25%–50%) than those who exercised less. In general, those who participated in at least 8.3 MET-hrs/wk improved their survival odds.

Exercise is beneficial not only for preventing cancer and helping survivors thrive but also for treating the disease. A study from the Journal of the National Cancer Institute (Courneya et al. 2013) found that exercise slowed breast cancer tumor growth in mice (by increasing oxygenation) and improved the effectiveness of chemotherapy.

Lung Cancer

While exercise does not reduce mortality risk from lung cancer as much as it does from breast cancer, risk reduction is still about 20% (Ballard-Barbash et al. 2006; Lee & Oguna 2006). Evidence shows that higher volumes likely protect against lung cancer the most; however, this is harder to discern owing to complications from smoking or respiratory disease. Smokers are, generally speaking, not exercisers or healthy eaters; thus intervening factors confuse the results. The protective effect is also less obvious in women than it is in men.

Researchers in Norway studied smokers' tolerance levels for a program of "high-intensity endurance and strength training" following lung cancer surgery (Edvardsen et al. 2015). They exposed subjects who were 5–7 weeks postsurgery to 60 minutes of exercise, 3 times per week, for 20 weeks. Not only was exercise well-tolerated, but subjects improved their peak oxygen uptake, muscular strength, total muscle mass, functional fitness and quality of life. Thus, people can exercise relatively soon after lung surgery (Edvardsen et al. 2015).

Prostate Cancer

Here's a bit of bad news for those exercising to reduce their prostate cancer risk. An inverse relationship between physical activity and prostate cancer is not apparent (IARC 2002). Several mechanisms—including hormones, energy balance, IGF-1, immunity and antioxidant defense mechanisms—all have a role (McTiernan 2006). A study by Giovannucci and associates (2005) found that regular, vigorous exercise slowed the progression of prostate cancer in men over 65 years.

Another study looked at how exercise in 10 healthy men might affect prostate tumor cell growth (Rundqvist et al. 2013). Researchers took blood samples before and after 60 minutes of vigorous exercise and then mixed the samples with prostate tumor cells. In the blood samples drawn after exercise, the scientists found, tumor cell growth was inhibited by 31%. While the exact mechanism is unclear, the results are promising for future studies. One theory is that tumor-suppressing natural killer cells (discussed earlier in the article) are activated by factors released during exercise, and are responsible for the immediate protection.

Exercise Is a Good Choice, Regardless

The knowledge that not exercising is actually a risk factor for cancer, like smoking, is critical. Of course, always encourage clients to work closely with their physicians, and tailor your program according to the individual's status. Any exercise is better than none, and frequent activity is crucial for obtaining and maintaining adaptations, as well as lowering stress and developing a strong movement habit. Exercise is a tool we can use to manipulate our hormones and epigenetics, while improving our psychological function and developing a holistic approach to fighting cancer.

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