Physical activity and cancer prevention: animal-tumor models

PURPOSE: The aims of this paper are to briefly review the types of animal and tumor models used in carcinogenesis studies and to consider their utility in studies of physical activity and cancer. METHODS: Published data from animal studies using tumor models for which corresponding human epidemiologic evidence shows a clear association between physical activity and that cancer (i.e., colon and breast) are reviewed. RESULTS: A variety of animal-tumor models have been used in cancer studies including spontaneous tumors, chemically induced tumors, orthotopic and syngeneic tumor transplantation, injected tumors, and genetically engineered (transgenic, knockout, and mutation-induced) mice with a predisposition to neoplasia. The most commonly used animal-tumor model in the study of physical activity has been the chemical carcinogenesis model. Methodological limitations of the various animal-tumor models are described including variations in dosing, route of administration, and type of carcinogen used, and forced versus voluntary exercise effects. CONCLUSIONS: Animal-tumor models are useful for understanding specific aspects of the carcinogenesis process and the interaction of this process with exercise. There is no one animal-tumor model that is ideally suited for studying physical activity interventions. However, animal-tumor models can be viewed as complementary to epidemiologic studies and human clinical trials in the area of physical activity and cancer prevention.     

Physical activity and dementia: The need for prevention trials

Dementia is a common and debilitating disease that will increase dramatically for the next 50 years unless a prevention or treatment is identified. This review summarizes the evidence that physical activity is associated with a reduced risk of dementia in older adults and recommends that prevention trials be performed to determine whether this association is causal.     

Physical activity and cancer

Evidence that physical activity may protect against various forms of cancer is examined in relation to occupational demands, leisure activities and participation in sport while at university. The variety of forms of neoplasm and equally varied physical activity histories militate against finding any simple relationship between the risk of malignancy and the individual's physical activity history. Nevertheless, five of seven major occupational studies suggest that a physically active occupation offers some protection against colon cancer, and an application of Bradford Hill's criteria generally supports the causal nature of the relationship between physical inactivity and an increased risk of intestinal neoplasia. However, existing reports are by no means conclusive; there thus remains a need for well-designed epidemiological studies of this issue. Data from one laboratory also suggest that in women a history of active leisure is associated with a reduced prevalence of breast and reproductive system cancers. Physical activity potentially encourages a healthy lifestyle, and it could have more direct effects on certain forms of carcinogenesis (for instance, by a speeding of gastro-intestinal transit, or a moderation of sex hormone levels). However, there are also potential negative effects from some types of exercise, particularly an excessive exposure to ultra-violet light in certain water sports. Since moderate exercise elevates mood and helps to conserve lean tissue, it may finally be a helpful component of treatment after a neoplasm has been diagnosed.     

Physical activity interventions for cancer survivors

Obesity and a sedentary lifestyle are highly prevalent in cancer survivors, and a growing number of publications have shown statistically and clinically significant associations between low levels of physical activity, obesity and cancer recurrence and death. Adoption and maintenance of physical activity is a difficult challenge for healthy adults, and is likely to be even more difficult after a cancer diagnosis. More effective strategies to increase physical activity in cancer survivors should be explored. The purpose of this paper is to (1) provide a rationale for physical activity interventions and programmes for cancer survivors, and (2) discuss successful approaches to adopting and maintaining physical activity to meet evidence based recommendations and ultimately improve cancer survival and overall survival. Since a majority of cancer survivors are not currently participating in recommended levels of physical activity, resulting in greater disease risk and health care costs, targeted exercise therapy has the potential to benefit a large number of cancer survivors. Cancer survivors should seek out the opportunities that exist towards being physically active, and oncologists should also become aware of the benefits of exercise, assist their patients by endorsing existing physical activity guidelines, and refer their patients to certified cancer exercise trainers.     

Physical activity and cancer prevention--mechanisms

PURPOSE: This paper presents potential mechanisms by which exercise or physical activity may affect cancer development. METHODS: Analysis of published and unpublished experimental and epidemiological data from the cancer-activity literature and from other fields of study are compiled to provide a summary of potential mechanisms by which exercise may mediate cancer development. RESULTS: Exercise appears to have a beneficial effect relative to cancer development, and the reader is referred to other sections of this symposium. To date however, the mechanism(s) remains unknown. Potential mechanisms influenced by exercise include alterations in steroid hormones or insulin/insulin-like growth factors, immune modulation, alterations in free radical generation, changes in body composition or weight, and direct effects on the tumor. Cancer is a complex process. It is clear that multiple mechanisms may be operative and that the characteristics of the individual, type of exercise, as well as type of cancer and stage of carcinogenesis will affect which mechanisms may affect the disease. More experimental research in both animal models and in human clinical studies is needed to understand the basic biological mechanisms underlying the effect of physical activity on cancer. CONCLUSION: In general, physical activity is associated with reduced risk of cancer development, yet to date, the mechanisms remain unknown.     

Physical activity and breast cancer

Knowledge of the relationships between risks and benefits of a given lifestyle is fundamental to being able to change life-long habits responsible for the development of pathological processes. Breast cancer is a widely studied pathology of vast social importance. It is important to identify the most appropriate lifestyle to give the organism the necessary tools to prevent tumour development. Physical exercise can act on and modify the different risk factors responsible for the development of both the primary pathology of breast cancer and relapses, thus reducing mortality. The various hypotheses of the biological routes through which physical activity can reduce risk indicate involvement of the following mechanisms: reduction in body weight, reduction in circulating levels of sex hormones, reduction in insulin resistance, reduction in leptin and adiponectin and modulation of the immune system. Recent discoveries on the mechanisms of cancer development indicate that cancer is the chronic pathology par excellence, and it is highly unlikely that it will be possible to eliminate it by concentrating all our efforts on tumour treatment techniques alone; it will be necessary to cure the whole organism in depth. Physical activity can be considered an “anticancer biology” that succeeds in exploiting the breakthroughs of medicine and our natural defences.     

Physical activity and colorectal cancer

Physical activity has been shown to reduce risk of colon cancer. Some studies have shown site-specific associations while others have not. The inverse association between physical activity and colon cancer is consistent although only 7 of 13 studies that have collected both colon and rectal cancer data in the same manner report reduced risk for rectal cancer; four of these studies detected statistically significant inverse associations. The frequency, duration and intensity of activity are important components of a public health message to reduce risk of colon cancer through performance of physical activity. However, difficulties in estimating the exact amount of activity needed and frequency and intensity of activity result in only crude estimates of dose needed for a protective effect. Much of the literature suggest that more intense activity is needed to reduce colon cancer risk and that somewhere between 3.5 and 4 hours of vigorous activity per week may be needed to optimise protection. Several biological mechanisms have been proposed to explain the association between physical activity and colon cancer; many of these mechanisms also support the observation that intense activities are most protective. Biological mechanisms include: physical activity increasing gut motility; enhancing the immune system; decreasing insulin and insulin-like growth factor levels; decreasing obesity; enhancing free radical scavenger systems; and influencing prostaglandin levels. The evidence taken together provides strong support for lack of physical activity being causally related to colon cancer. It has been estimated that 12-14% of colon cancer could be attributed to lack of frequent involvement in vigorous physical activity.     

Physical activity before and after diagnosis of colorectal cancer: disease risk, clinical outcomes, response pathways and biomarkers

Physical inactivity may be responsible for 13-14% of colon cancer, an attributable risk greater than family history. Epidemiological evidence shows an association between occupational and recreational physical activity and colon cancer, but has not established whether physical activity is protective against low-risk or more advanced adenomas. The evidence is inconclusive as to whether physical activity protects against rectal cancer and is conflicting with respect to whether physical activity has equal effects on male and female risk of colorectal cancer. The effect of exercise 'interventions' on the risk of colorectal cancer is currently not known. Also, although inferences can be made from epidemiological studies, no optimal exercise regimen can be confidently prescribed for protection against colorectal cancer. There is little available evidence for the benefits of physical activity before diagnosis of colorectal cancer for disease-specific survival and prognosis, and the clinical effects of an exercise intervention after diagnosis have not been investigated. There is some evidence that improvements in cardiorespiratory fitness reduce adverse effects from cancer treatment when physical activity is undertaken following diagnosis of colorectal cancer. Markers/mechanisms by which physical activity may protect against colorectal cancer and/or improve disease prognosis include gastrointestinal transit-time, chronic inflammation, immune function, insulin levels, insulin-like growth factors, genetics and obesity. Research evidence is, however, limited as to whether these markers are beneficially affected by physical activity, either before or after diagnosis of colorectal cancer.     

Physical activity and prevention of type 2 diabetes mellitus

The worldwide prevalence of type 2 diabetes mellitus is increasing at a rapid rate, predominantly because of changes in environmental factors interacting with individual genetic susceptibility to the disease. Data from 20 longitudinal cohort studies present a consistent picture indicating that regular physical activity substantially reduces risk of type 2 diabetes. Adjustment for differences in body mass index between active and inactive groups attenuates the magnitude of risk reduction, but even after adjustment, a high level of physical activity is associated with a 20-30% reduction in diabetes risk. The data indicate that protection from diabetes can be conferred by a range of activities of moderate or vigorous intensity, and that regular light-intensity activity may also be sufficient, although the data for this are less consistent. The risk reduction associated with increased physical activity appears to be greatest in those at increased baseline risk of the disease, such as the obese, those with a positive family history and those with impaired glucose regulation. Data from six large-scale diabetes prevention intervention trials in adults with impaired glucose tolerance or at high risk of cardiovascular disease indicate that increasing moderate physical activity by approximately 150 minutes per week reduces risk of progression to diabetes, with this effect being greater if accompanied by weight loss. However, this level of activity did not prevent all diabetes, with 2-13% of participants per annum who underwent lifestyle intervention still developing the disease. Thus, while 150 minutes per week of moderate activity confers benefits, higher levels of activity may be necessary to maximize diabetes risk reduction in those at high baseline risk of the disease. In contrast, those at low baseline risk of type 2 diabetes, e.g. people with a very low body mass index and no family history of diabetes, will remain at low risk of developing diabetes whether they are active or not. Thus, the amount of physical activity required to confer low risk of diabetes differs according to an individual's level of baseline risk. Consequently, a 'one size fits all' mass-population strategy may not provide the most appropriate approach when designing physical activity guidelines for the prevention of type 2 diabetes. Producing tailored guidelines with the specific aim of reducing risk of diabetes in high-risk populations may provide an alternative approach.     

Physical activity in the prevention of cardiovascular disease: an epidemiological perspective

This review of the epidemiological evidence regarding physical activity and cardiovascular disease (CVD) provides substantial evidence from many different populations that leisure time physical activity is associated with reduced risk of coronary heart disease (CHD) and cardiovascular mortality in both men and women and in middle-aged and older individuals. Physical activity appears to be a critical factor in both primary and secondary prevention of CHD. The studies indicate a dose-response relationship between overall physical activity and CVD, which is linear at least up to a certain level of activity. Prospective studies suggest that physical activity is also associated with reduced risk of stroke. The mechanisms underlying the protective effect of physical activity on CVD are still unclear. In recent years. the view that physical activity has to be vigorous to achieve a reduction in risk of CHD has been questioned. Overall, the evidence points to the benefit of continued regular moderate physical activity which does not need to be strenuous or prolonged and includes daily leisure activities such as walking or gardening which are readily attainable by large sections of the population. Taking up regular light or moderate physical activity in middle or older age confers significant benefit for CVD and all-cause mortality.     

Physical activity and cancer. An epidemiological perspective

This article reviews the existing epidemiological evidence on the association between physical activity and cancer. Relatively little is known about the role that increased physical activity may have in protecting humans from malignancy. Herein, studies are reviewed on the basis of the type of physical activity exposure studied: occupational or leisure time. Results suggest that if any consistencies emerge, there may be a protective effect of increased physical activity exposure upon cancer of the colon, and no effect on cancer of the rectum, in men. Increased physical activity in women during college years may protect against certain reproductive system cancers. Methodological deficiencies in assessment of physical activity (total exposure over lifetime) and in lack of control for other potential explanations block further, more solid conclusions. The fact that an association has been demonstrated in spite of these drawbacks, however, indicates the importance of further study. Suggested directions for future work are presented.     

Physical activity and cancer prevention--data from epidemiologic studies

PURPOSE: The aim of this paper is to examine whether physical activity plays any role in the prevention of cancer. METHODS: To accomplish this, data from published epidemiologic studies on the relation between physical activity and the risk of developing cancer were reviewed. RESULTS: The data are clear in showing that physically active men and women have about a 30-40% reduction in the risk of developing colon cancer, compared with inactive persons. Although the data are sparse, it appears that 30-60 min.d(-1) of moderate- to vigorous-intensity physical activity is needed to decrease risk. There is a dose-response relation, with risk declining further at higher levels of physical activity. It is also clear that physical activity is not associated with the risk of developing rectal cancer. With regard to breast cancer, there is reasonably clear evidence that physically active women have about a 20-30% reduction in risk, compared with inactive women. It also appears that 30-60 min.d(-1) of moderate- to vigorous-intensity physical activity is needed to decrease the risk of breast cancer, and that there is likely a dose-response relation. For prostate cancer, the data are inconsistent regarding whether physical activity plays any role in the prevention of this cancer. There are relatively few studies on physical activity and lung cancer prevention. The available data suggest that physically active individuals have a lower risk of lung cancer; however, it is difficult to completely account for cigarette smoking. There is little information on the role of physical activity in preventing other cancers. CONCLUSION: Physical activity is associated with lower risk of developing certain site-specific cancers, in particular colon and breast cancers.     

The wearable activity technology and action-planning trial in cancer survivors: Physical activity maintenance post-intervention

ObjectivesThe study objective was to assess whether moderate-to-vigorous intensity physical activity (MVPA) change in cancer survivors (n = 68, mean age = 64 years) was maintained 12-weeks following the Wearable Activity Technology and Action Planning (WATAAP) intervention. Secondary aims were to assess the effects of the intervention on blood pressure (BP) and body mass index (BMI), and to explore group differences between baseline and 24-weeks.DesignRandomized controlled trial.MethodsMVPA and sedentary behaviour were assessed using an accelerometer at baseline, the end of the intervention (12-weeks), and at 24-weeks. Generalised linear mixed models with random effects were used to examine between-group and within-group changes in MVPA, sedentary behaviour, BP and BMI.ResultsMVPA was significantly higher in the intervention group compared with the control group at 24-weeks following adjustment for known confounders (141.4 min/wk. (95% CI = 9.1 to 273.8), p = 0.036). At 24-weeks participants in the intervention group had maintained their increased levels of MVPA (change from 12-weeks = 8.8 min/wk.; 95% CI = −43 to 61; p = 0.74). The reduction in MVPA in the control group over the first 12-weeks was also maintained at 24-weeks (5.4 min/wk.; 95% CI = −3.6 to 4.6; p = 0.80). Secondary outcomes did not differ between groups at 24-weeks.ConclusionsOur results suggest distance-based interventions using wearable technology produce increases in MVPA that endure at least 12-weeks after the intervention is completed.     

Physical activity and breast cancer risk: the effect of menopausal status

Convincing epidemiologic evidence exists that physical activity reduces breast cancer risk. The association may differ by menopausal status, because stronger evidence for a risk reduction exists for postmenopausal than for premenopausal women. This review examines potential reasons for the differences in effect by menopausal status, including possible underlying biologic mechanisms.     

Physical activity levels among breast cancer survivors

INTRODUCTION: Obesity and weight gain are negative prognostic factors for breast cancer survival. Physical activity (PA) prevents weight gain and may decrease obesity. Little information exists on PA levels among cancer survivors. We assessed PA, including the proportion of breast cancer survivors engaging in recommended levels, by categories of adiposity, age, disease stage, and ethnicity in 806 women with stage 0-IIIA breast cancer participating in the Health, Eating, Activity, and Lifestyle Study. METHODS: Black, non-Hispanic white, and Hispanic breast cancer survivors were recruited into the study through Surveillance Epidemiology End Results registries in New Mexico, Western Washington, and Los Angeles County, CA. Types of sports and household activities and their frequency and duration within the third yr after diagnosis were assessed during an in-person interview. RESULTS: Thirty-two percent of breast cancer survivors participated in recommended levels of PA defined as 150 min x wk(-1) of moderate- to vigorous-intensity sports/recreational PA. When moderate-intensity household and gardening activities were included in the definition, 73% met the recommended level of PA. Fewer obese breast cancer survivors met the recommendation than overweight and lean breast cancer survivors (P < 0.05). Fewer black breast cancer survivors met the recommendation compared with non-Hispanic white and Hispanic breast cancer survivors (P < 0.05). CONCLUSIONS: Most of the breast cancer survivors were not meeting the PA recommendations proposed for the general adult population. Efforts to encourage and facilitate PA among these women would be an important tool to decrease obesity, prevent postdiagnosis weight gain, and improve breast cancer prognosis.