by Victoria A. Fisher, M.P.H.
How does physical activity influence cancer risk? DCEG scientists are investigating which cancers are affected by physical activity, what type of activity, how much activity makes a difference, effects on survival following a cancer diagnosis, and the biological mechanisms underlying these relationships.
There is strong evidence that physical activity reduces the risk of breast, colon, and endometrial cancer. Associations with other cancers are less clear, but Charles E. Matthews, Ph.D., Steven C. Moore, Ph.D., M.P.H., and colleagues are making strides to expand the current knowledge base on the range of cancer sites associated with physical activity and the relationship between amount of activity and cancer.
The focus of research on physical activity has recently shifted from activities associated with one’s occupation to leisure-time activity. Dr. Moore is leading a team of investigators who are using pooled data within the NCI Cohort Consortium to study the association between leisure-time physical activity and 26 different types of cancer, some rare or not previously studied. According to Dr. Moore, “This is the largest study to date of physical activity and cancer. Our results may broaden the number of cancers linked to physical activity and may suggest new avenues for prevention.”
Research indicates that physical activity also affects overall mortality from all causes combined. In a previous study within the Cohort Consortium, Dr. Moore and colleagues found that leisure-time physical activity was associated with longer life expectancy, even at relatively low levels of activity and regardless of body weight (PubMed Abstract: Leisure time physical activity of moderate to vigorous intensity and mortality: a large pooled cohort analysis.Moore et al., 2012).
“Our findings highlight the important contribution that leisure-time physical activity in adulthood can make to longevity,” Dr. Moore said.
Ongoing studies will extend our understanding of the relationship between the amount of physical activity and mortality. DCEG fellow Hannah Arem, Ph.D., M.H.S., is evaluating the association between levels of physical activity beyond the federally recommended minimum and mortality, with particular interest in defining the upper limit of benefit, or possible harm, associated with very high levels of exercise.
In recent years, sedentary behavior has emerged as a risk factor for disease that is distinct from and independent of leisure-time physical activity. Sedentary behavior is linked with diabetes, obesity, and cardiovascular disease; it can also increase the risk of certain cancers, most notably colorectal and endometrial (Graphic depicting various health effects of sitting.Washington Post Infographic 2014—pdf, 31.5 MB), (Text-only version of Washington Post Infographic—pdf, 54KB). New insights about the adverse health effects of sitting have helped us understand some of the limitations of the prevailing strategy, regular exercise, to reduce these risks, as well as opportunities to augment this strategy. DCEG investigators have helped define the magnitude of the problem, quantify the health risks associated with sedentary behaviors, and describe the risks associated with reducing sedentary time.
“The average adult spends more than half their day sitting or in sedentary behaviors,” Dr. Matthews said. “We’re learning that exercise alone may not be enough to reduce the risk of cancer and other diseases.”
Using data from the NIH-AARP Diet and Health Study, Dr. Matthews and colleagues found that higher amounts of sitting time and television viewing were associated with mortality, even after adjustment for exercise participation (PubMed Abstract: Amount of time spent in sedentary behaviors and cause-specific mortality in US adults.Matthews et al., 2012). Dr. Matthews takes this message to heart; he is often seen standing in seminars or walking on the tread-desk in his office.
DCEG investigators are also curious about the tradeoffs between sedentary behavior and physical activity. Dr. Matthews and colleagues recently estimated the mortality benefits associated with reducing sedentary time by an hour and replacing with different types of physical activity (PubMed Abstract: Mortality Benefits for Replacing Sitting Time with Different Physical Activities.Matthews et al., 2015).
“We found that replacing sitting time with any type of activity was beneficial for less active adults,” Dr. Matthews said. “For more active adults, mortality was only lower for those who replaced sitting time with purposeful exercise.” DCEG fellow Sarah Keadle, Ph.D., M.P.H., is examining television viewing as a modifiable risk factor.
Sleep is another health behavior that relates to sedentary behavior and physical activity; researchers are evaluating sleep as part of the full 24-hour measurement period. A recent paper by DCEG fellow Qian Xiao, Ph.D., and Dr. Matthews looked at the interrelationships of sleep, physical activity, sedentary behavior, and body mass index with mortality (PubMed Abstract: Sleep duration and total and cause-specific mortality in a large US cohort: interrelationships with physical activity, sedentary behavior, and body mass index.Xiao et al., 2014).
According to Dr. Matthews, “We are finding that sleep, sedentary behavior, and physical activity are all independently associated with mortality. Each behavior seems to have unique physiologic functions and patterns of risk for mortality.”
DCEG investigators are also assessing the benefits of physical activity in cancer survivors, a population quickly growing thanks, in part, to improved cancer treatments and early detection. Evidence from observational prospective studies suggests that physical activity after cancer diagnosis may be associated with a reduced risk of cancer recurrence and improved overall mortality among multiple cancer survivor groups, including breast, colorectal, prostate, and ovarian cancer.
Dr. Arem and Dr. Matthews recently published a paper on exercise and television viewing habits (the most prevalent leisure-time sedentary behavior) before and after diagnosis among colorectal cancer survivors (PubMed Abstract: Pre- and postdiagnosis physical activity, television viewing, and mortality among patients with colorectal cancer in the national institutes of health-AARP diet and health study.Arem et al., 2015). Increasing exercise and minimizing TV viewing both were associated with lower mortality risk among colorectal cancer survivors.
“This study gives us a snapshot of physical activity and sedentary behaviors among colorectal cancer survivors and how these factors might influence mortality,” according to Dr. Arem.
Regular physical activity helps maintain a healthy body weight and may prevent cancers directly and indirectly, by mechanisms that include regulating hormones and providing beneficial effects on insulin and glucose metabolism, inflammatory markers, and the immune system.
“Research by DCEG investigators continues to add evidence and increase our understanding of how physical activity affects cancer...”
Dr. Stephen Chanock
Using information recorded by a lightweight accelerometer worn by participants in the National Health and Nutritional Examination Survey (NHANES), Dr. Matthews and colleagues reported the first objective data on the amount of time spent in overall sedentary behaviors in a nationally representative sample (PubMed Abstract: Sedentary time and cardio-metabolic biomarkers in US adults: NHANES 2003-06.Healy et al., 2011). After adjusting for the effect of exercise, the amount of daily sedentary time was linked to levels of C-reactive protein, insulin, and other cardio-metabolic biomarkers. Future DCEG metabolomic studies will continue to evaluate associations between accelerometer-based measures of active and sedentary time.
DCEG investigators are leveraging better measurements of physical activity and sedentary behavior with new metabolism assays, like the urinary estrogen assay. Using data and samples collected from premenopausal women in the Nurses’ Health Study II, Dr. Matthews, Regina G. Ziegler, Ph.D., M.P.H., and colleagues from Harvard University recently found that greater leisure-time physical activity was associated with lower urinary estradiol and several metabolites in the 16-hydroxylation pathway (PubMed Abstract: Association between physical activity and urinary estrogens and estrogen metabolites in premenopausal women.Matthews et al., 2012). Both measures have been associated with reduced risk of breast cancer in previous studies.
Ongoing work will examine the effect of exercise intervention on estrogen metabolism in post-menopausal women. Investigators will also evaluate estrogen metabolism as a potential mediator of the energy balance-breast cancer association.
The validity of etiologic studies is dependent on the breadth, accuracy, and precision of the measured exposures or endpoints. Due to their size, prospective studies of cancer have typically relied on the self-reported questionnaire-based approach to assess physical activity. Though contemporary questionnaires ask for more detailed information about exercise and sedentary behavior, using only questionnaires may impede full understanding of the relationship between physical activity and cancer.
Dr. Matthews reports, “We have developed a new internet-based recall method that does a better job of capturing the full range of daily activities, including sleep, physical activity, and sedentary behaviors, perhaps with more accuracy than our traditional questionnaire-based methods.”
In collaboration with Heather Bowles, Ph.D., Amy Subar, Ph.D., M.P.H., R.D., and Gordon Willis, Ph.D., from the NCI Division of Cancer Control and Population Sciences, Dr. Matthews and Dr. Moore created and are testing the new web-based tool Physical Activities Completed over Time in 24 Hours (ACT24) for use in large-scale studies. The tool will be employed in future NIH-AARP Diet and Health Studies as well as in other cohorts.
Stephen J. Chanock, M.D., Director of DCEG, states, “In an increasingly sedentary world, it is vital to explore the links between physical activity, sedentary behaviors, and health outcomes like cancer. Research by DCEG investigators continues to add evidence and increase our understanding of how physical activity affects cancer, which will in turn lead to stronger and better recommendations about healthy lifestyle.”