Don't take cancer sitting down

A new survivorship research agenda

Authors

  • Brigid M. Lynch PhD,

    Corresponding author
    1. Physical Activity Laboratory, Baker IDI Heart and Diabetes Institute, Melbourne, Victoria, Australia
    2. Melbourne School of Population Health, Faculty of Medicine, Dentistry and Health Sciences, The University of Melbourne, Melbourne, Victoria, Australia
    • Corresponding author: Brigid M. Lynch, PhD, Physical Activity Laboratory, Baker IDI Heart and Diabetes Institute, Level 4, 99 Commercial Road, Melbourne VIC 3004 Australia; Fax: (011) 61 3 8532 1100; brigid.lynch@bakeridi.edu.au

    Search for more papers by this author
  • David W. Dunstan PhD,

    1. Physical Activity Laboratory, Baker IDI Heart and Diabetes Institute, Melbourne, Victoria, Australia
    2. School of Population Health, The University of Queensland, Brisbane, Queensland, Australia
    3. School of Public Health and Preventive Medicine, Monash University, Melbourne, Victoria, Australia
    4. School of Exercise and Nutrition Sciences, Deakin University, Melbourne, Victoria, Australia
    Search for more papers by this author
  • Jeff K. Vallance PhD,

    1. Faculty of Health Disciplines, Athabasca University, Athabasca, Alberta, Canada
    Search for more papers by this author
  • Neville Owen PhD

    1. Melbourne School of Population Health, Faculty of Medicine, Dentistry and Health Sciences, The University of Melbourne, Melbourne, Victoria, Australia
    2. School of Population Health, The University of Queensland, Brisbane, Queensland, Australia
    3. School of Public Health and Preventive Medicine, Monash University, Melbourne, Victoria, Australia
    4. Behavioral Epidemiology Laboratory, Baker IDI Heart and Diabetes Institute, Melbourne, Victoria, Australia
    Search for more papers by this author

Abstract

Cancer survival is associated with considerable physical and psychosocial burden. Broadly accessible, nonpharmacologic measures that may extend disease-free survival, limit comorbid disease, and enhance quality of life are required. Sedentary behavior (too much sitting) is now understood to be a health risk that is additional to, and distinct from, the hazards of too little exercise. Of particular note, it is associated with adiposity, insulin resistance, and markers of inflammation. Therefore, it is plausible that sedentary behavior may contribute to adverse cancer outcomes (disease progression, recurrence, or death) and to the development of comorbid chronic disease. Initial studies indicate that cancer survivors spend two-thirds of their waking hours sitting. Among colorectal cancer survivors, sedentary behavior may contribute to all-cause and disease-specific mortality, weight gain, comorbid cardiovascular disease, and diminished quality of life. There is a need for dose-response evidence, and for a broader understanding of the underlying mechanisms by which prolonged sitting time may affect cancer survivors' health. Cancer 2013;119:1928–1935. © 2013 American Cancer Society.

INTRODUCTION

There are now nearly 14 million cancer survivors living in the United States. This figure is projected to rise to 18 million within 10 years, largely because of population ageing and ongoing improvements in cancer care.[1] Cancer survival is associated with significant decrements in health status and an increased risk of death from noncancer causes.[2] The “burden” of cancer survival includes ill health and premature death because of comorbid chronic diseases, particularly type 2 diabetes and cardiovascular disease.[3] However, it has been demonstrated that modifiable health behaviors can redress such morbidity among cancer survivors.[4] Regular participation in moderate-intensity to vigorous-intensity physical activity—such as brisk walking or structured exercise training programs—is associated with prolonged survival,[5] diminished treatment side effects, and enhanced quality of life.[8, 9]

The use of accelerometers to objectively assess physical activity in population-based studies has provided detailed information on how adults actually spend their waking hours. Accelerometers are small electronic devices, typically worn on the hip, which record acceleration data that can be downloaded to a computer to provide a precise perspective based on established movement-count cutoff points. Within the general adult population, it is striking that such a large proportion of each day is spent sedentary (up to 70%, primarily involving sitting). Less than 5% of waking hours are spent in moderate-intensity to vigorous-intensity activity, and light-intensity activity accounts for the remainder of the measured day.[10, 11] This new understanding of the relative volumes of sedentary and active time has led to a shift in the physical activity and health paradigm.[12, 13] Instead of focusing on activities that make up only a fraction of an individuals' day, there is now the impetus to study the contributions that sedentary behavior and light-intensity physical activity can make to health outcomes. This contemporary research focus is of particular relevance for cancer survivors, many of whom spend less than 1% of their waking hours engaged in the recommended types of moderate-intensity to vigorous-intensity physical activities.[14, 15]

Few studies have considered sedentary behavior in a cancer survival context, despite adverse associations with the mechanisms operative in carcinogenesis.[16] In this commentary, we summarize relevant research findings on the health consequences of adults' sedentary behavior and propose the case for why this is now an important field of scientific enquiry for cancer survivorship. We discuss directions for future research and propose a conceptual framework to guide this research. Finally, we highlight the potential health benefits for cancer survivors that may result from reducing sedentary time.

The Health Consequences of Sedentary Behavior Are Additional to Those of Physical Inactivity

The health benefits of regular participation in physical activity are now well established: it reduces the risk of all-cause mortality, cardiovascular disease, type 2 diabetes, some cancers, and depression.[17] Public health guidelines—such as those issued by the US Department of Health and Human Services[18]—recommend that adults should accumulate either 150 minutes of moderate-intensity physical activity or 75 minutes of vigorous-intensity physical activity each week. These prescribed levels of moderate-intensity and vigorous-intensity activity are additional to the light-intensity activities of daily living (such as standing, walking slowly, and general moving about). Technologic advances achieved in previous decades automated many of our daily tasks and thereby eroded or diminished this level of light-intensity physical activity.[19] Now, at least half—and up to two-thirds—of adults' waking hours are spent sitting.[12]

Emerging Evidence That Sedentary Behavior May Increase the Risk of Cancer Progression

There is a growing body of research evidence that links sedentary behavior with cancer risk. Sedentary behavior—often assessed as a self-reported estimate of overall daily sitting or television viewing time in epidemiologic studies—has been associated with an increased risk of ovarian,[20, 21] colorectal,[22, 23] and endometrial cancers[24] and of non-Hodgkin lymphoma in women,[29] but not with an increased risk of breast cancer[30, 31] or renal cell carcinoma.[32] Two prospective cohort studies have demonstrated a statistically significant association of sedentary behavior with overall cancer mortality.[33, 34] On the basis of this epidemiologic evidence, the American Cancer Society now includes recommendations to limit sitting time within their Guidelines on Nutrition and Physical Activity for Cancer Prevention.[35]

To date, only 1 study has examined whether sedentary behavior is associated with site-specific cancer survival. In a recently published analysis, 2293 men and women with nonmetastatic colorectal cancer were identified within the Cancer Prevention Study-II Nutrition Cohort. Self-reported leisure-time sitting was ascertained at baseline (a mean of 7 years before diagnosis) and at routine follow-up time points. The first assessment conducted after each participant's colorectal cancer diagnosis was used as the postdiagnosis measure of sitting time (a mean of 2 years after diagnosis). Prediagnosis sitting time was associated with all-cause mortality (<3 hours daily vs ≥6 hours daily: relative risk [RR], 1.36; 95% confidence interval [CI], 1.10-1.68), and postdiagnosis sitting time was associated with all-cause mortality (RR, 1.27; 95% CI, 0.99-1.64) and colorectal carcinoma-specific mortality (RR, 1.62; 95% CI, 1.07-2.44).[36]

There are several mechanisms that make the link between sedentary time and disease progression, and hence poorer survival, biologically plausible.[16] Obesity has poor prognostic implications for cancers of the breast, colon, and prostate.[37] There is a plausible and increasingly well understood mechanism by which sedentary behavior may contribute to obesity. Time in sedentary behavior generally displaces time spent in light-intensity physical activity,[38] and such a shift reduces overall cumulative daily energy expenditure. Displacement of 2 hours per day of light-intensity activity (2.5 metabolic equivalents [METS]) by sedentary behavior (1.5 METs) would reduce activity energy expenditure by approximately 2 MET hours per day. For a 70-kg individual, this change in behavior would result in a decrease in daily energy expenditure equivalent to 140 kcal per day and potentially a 0.5-kg weight gain over 1 month. For cancer survivors, such sedentary behavior-driven energy imbalance may contribute both to poorer cancer-specific outcomes and to comorbidities.[37]

Aspects of metabolic dysfunction provide another pathway by which sedentary behavior may contribute to disease progression. There is increasing evidence that hyperinsulinemia, insulin resistance, and perturbations in the insulin-like growth factor axis are associated with cancers of the breast, colon, pancreas, and prostate.[39] These mechanisms also are associated with an increased risk for cancer recurrence and death.[40] Cross-sectional studies have demonstrated significant associations between sedentary behavior and biomarkers of metabolic dysfunction; however, clear evidence of significant associations has not emerged from the small number of prospective studies that have been conducted to date.[41, 42] Sedentary behavior plausibly may affect metabolic function through increased adiposity and decreased skeletal muscle mass. The sustained muscular inactivity that occurs during prolonged periods of sitting may reduce glucose uptake through blunted translocation of glucose transporter type 4 (GLUT-4) glucose transporters to the skeletal muscle surface.[43]

Chronic inflammation is also acknowledged as a risk factor for most types of cancer.[44] Inflammation can induce cell proliferation, microenvironmental changes, and oxidative stress, which, in turn, deregulates normal cell growth and promotes progression and malignant conversion.[45] It has been proposed that individuals who engage in high volumes of sedentary behavior exhibit a metabolic and inflammatory response that evolved to help our Paleolithic ancestors survive injury and fight infection.[46] This hypothesis is supported by epidemiological evidence demonstrating associations of sedentary behavior with inflammatory biomarkers in a small number of observational studies.[47]

Reducing the Sedentary Behavior of Cancer Survivors Could Prevent and Mitigate Comorbid Chronic Disease

Cancer survivors have an elevated risk for a range of concomitant chronic conditions that can be attributed to advancing age, genetic predisposition, and shared lifestyle risk factors.[3, 52] Improving lifestyle after a cancer diagnosis may mitigate existing comorbid conditions and reduce the risk of developing further chronic disease.[53, 54] Over the past decade, there has been a rapid accumulation of evidence linking sedentary behavior with several chronic conditions, including obesity, diabetes, and cardiovascular disease.[12] A recent meta-analysis of 18 epidemiological studies concluded that sedentary behavior was significantly associated with a doubling of the risk of diabetes and cardiovascular events.[55] These diseases represent some of the most commonly observed comorbid conditions in cancer survivors.[56]

Emerging Evidence on Sedentary Behavior in Cancer Survivors

An Australian longitudinal study of 1966 colorectal cancer survivors provided the first evidence that sedentary behavior has deleterious associations with health outcomes in cancer survivors. Watching 5 hours or more (vs 2 hours or less) of television per day was associated with: a mean increase in body mass index (BMI) of 0.71 kg/m2 over approximately 18 months,[57] a 16% lower total quality of life score,[58] and de novo ischemic heart disease.[53] Two studies from the United States have considered the associations of sedentary behavior with psychosocial outcomes in breast cancer survivors. A cross-sectional study of 483 breast cancer survivors from rural counties of a Midwest state indicated that daily sitting time was associated with fatigue, but not with depressive symptoms.[59] However, prospective analyses of 710 women from the Health, Eating, Activity, and Lifestyle (HEAL) Study indicated no significant associations between time spent in sedentary behaviors and fatigue or health-related quality of life.[60] Finally, a cross-sectional study of Canadian kidney cancer survivors indicated no overall association between self-reported sitting time and quality of life, but an inverse association with physical and functional aspects of quality of life was reported in survivors aged <60 years.[61]

Two published studies have characterized the sedentary time of cancer survivors using objective device-based measurement. These studies examined the cross-sectional associations of accelerometer-assessed sedentary time with measures of adiposity, using data from the National Health and Nutrition Examination Survey (NHANES) (2003-2006). Sedentary time was associated with BMI, waist circumference, and fasting insulin levels in breast cancer survivors, but these associations were attenuated by the addition of moderate-intensity to vigorous-intensity physical activity to the models.[14] Sedentary time was not associated significantly with adiposity in prostate cancer survivors.[15] In addition, the findings from those studies suggest that the physical activity of cancer survivors derived from self-reported measures may be substantially inflated. On average, breast cancer survivors recorded 4 minutes of moderate-intensity to vigorous-intensity physical activity per day[14]; for prostate cancer survivors it was 6 minutes.[15]

Figure 1 highlights the very small proportion of cancer survivors' daily hours comprised of moderate-intensity to vigorous-intensity physical activity. Compared with women and men aged >60 years from the general NHANES population, breast and prostate cancer survivors spend less time in moderate-intensity to vigorous-intensity and light-intensity physical activity and spend more sedentary time. During an average accelerometer wear-time period of approximately 14 hours per day, breast and prostate cancer survivors accumulate approximately 9 and a half hours of sedentary time.

Figure 1.

Accelerometer-assessed, wear time-adjusted sedentary time, light-intensity physical activity, and moderate-intensity to vigorous-intensity physical activity are illustrated for men aged ≥60 years, women aged ≥60 years, prostate cancer survivors, and breast cancer survivors from the National Health and Nutrition Survey (2003-2006). Note the higher levels of sedentary time in prostate and breast cancer survivors versus men without cancer (P = .06) and women without cancer (P < .01).

To date, insufficient evidence has accumulated to draw strong conclusions about the role of sedentary behavior in cancer survivorship. However, emerging evidence suggests that sedentary behavior is associated with markers of adiposity, comorbidities, and psychosocial health outcomes among colorectal and breast cancer survivors.[14, 53, 57] It is clear that additional research is needed to establish whether ameliorating increases in, or reducing, sedentary behavior after diagnosis is a viable new strategy to help improve health outcomes among cancer survivors. In the section below, we describe a research strategy for addressing the considerable gaps in knowledge.

A Suggested Strategy for Advancing Knowledge in the Sedentary Behavior and Cancer Survivorship Field

The behavioral epidemiology framework[62] is a useful tool for conceptualizing the hierarchical phases of research to be conducted to develop a comprehensive evidence base. Figure 2 lists the research phases applicable for sedentary behavior and cancer survivorship research. Evidence is now accumulating in phase 1 (determining associations of sedentary behavior with health outcomes in cancer survivors), phase 3 (characterizing the prevalence and variations in sedentary behavior after cancer diagnosis and treatment), and phase 4, (identifying determinants of sedentary behavior). There is a plethora of opportunities for further research with cancer survivors in all of these research phases.

Figure 2.

A behavioral epidemiology framework for research in sedentary behavior and cancer survivorship.

For research in phase 1, prospective studies are needed to determine the association of sedentary behavior with site-specific cancer survival. It is also important to understand how sedentary behavior contributes to morbidity among cancer survivors: studies investigating associations with comorbid chronic illness, disability, quality of life, and other patient-reported outcomes are required. Observational studies also are needed to examine associations with prognostic biomarkers. How sedentary behavior may be associated with mechanisms operative in cancer pathogenesis have only begun to be explored, and there are numerous avenues for enquiry to be pursued. Research in phase 2 speaks to the need to improve measurement of sedentary behavior among cancer survivors. Studies to date have mostly used simple self-report measures to estimate sedentary behavior, such as a single item pertaining to television viewing time.[16] There are now sophisticated devices (accelerometers, inclinometers) for collecting objective sedentary time data. However, these devices cannot differentiate between different contexts or types of sedentary behaviors, nor is it always practical or affordable to use accelerometers or inclinometers in large epidemiologic studies. Hence, the development of comprehensive self-report measures of sedentary behavior and specific testing among cancer survivors are required.[16] Such measures, when used in conjunction with objective measures, will enable the collection of high-quality data for phases 3 and 4.

Classifying the characteristics of the most sedentary individuals and the contexts in which sedentary behavior is most likely to occur (phase 4) is necessary to identify prime candidates for interventions to reduce sedentary time. Context-specific studies using the appropriate self-report methods would help us understand how environmental attributes influence sedentary behaviors.[63] The feasibility and efficacy of interventions to reduce sedentary time then need to be tested rigorously, ideally as randomized controlled trials (phase 5). Such trials also will be needed to compare the relative merits of various types of interventions that reduce or break up extended periods of sedentary behavior. It is noteworthy that all of these phases of research are required to inform public health guidelines and policy (phase 6), which currently do not exist in the cancer survivorship context.

Potential Benefits To Be Gained by Reducing Sedentary Behavior Among Cancer Survivors

Identifying ways in which aspects of the general health of cancer survivors can be improved will decrease morbidity in this population and subsequently will decrease the associated economic and health burden. The protective effects of regular physical activity are undisputed and should never be underscored. In particular, there are clinically relevant benefits associated with vigorous-intensity physical activity, such as maintaining or improving cardiopulmonary function.[64] However, the overwhelming majority of cancer survivors do not participate in sufficient physical activity, as defined by public health guidelines.

Changing cancer survivors' physical activity levels remains a challenge, because gains achieved through behavioral interventions often are modest, short-lived, and diminish postintervention.[65] Although there are many specific health benefits to be gained by continuing to promote physical activity, targeting sedentary behavior may be a more feasible and appropriate approach for a wider proportion of cancer survivors (including individuals for whom exercise contraindications exist). Adverse side-effects of reducing or breaking up prolonged periods of sitting time among cancer survivors are likely to be minimal; nevertheless, empirical evidence to that effect would be informative. Risks arising from recommendations directed at cancer survivors to spend less time sitting and more time engaged in light-intensity physical activity (standing, walking, general tasks of daily living) may need to be addressed clinically and specifically among those with lower body muscle or joint problems or osteoarthritis. Interventions to reduce sitting time among older adults (aged ≥60 years) have been successfully delivered and have generated positive outcomes.[66] These findings suggest that the sedentary behavior of cancer survivors is likely to be amenable to change.

In conclusion, many cancer survivors are highly motivated to adopt behavioral changes that will enhance their quantity and quality of life. Reducing sedentary behavior holds promise as new strategy for improving health outcomes for cancer survivors. On the basis of the small but convincing body of evidence linking sedentary behavior with colorectal, endometrial, and ovarian cancer risk, recommendations to limit sedentary behavior for cancer prevention are now made within the American Cancer Society's Guidelines on Nutrition and Physical Activity for Cancer Prevention.[35] With the accumulation of a broader body of research findings relating to cancer survivorship, within the phases of the behavioral epidemiology framework that we have described, we would anticipate that similar recommendations will begin to be formulated for cancer survivors in the future.

FUNDING SOURCES

Dr. Lynch is supported by a Public Health Training Fellowship from the National Health and Medical Research Council (no. 586727), Dr. Dunstan is supported by an Australian Research Council Future Fellowship, Dr. Vallance is supported by a Population Health Investigator Award (Alberta Innovates-Health Solutions) and a New Investigator Award (Canadian Institutes of Health Research), and Dr. Owen is supported by a Senior Principal Research Fellowship (National Health and Medical Research Council; no. 1003960). Baker IDI Heart and Diabetes Institute receives support from the Victorian Government's Operational Infrastructure Support Program.

CONFLICT OF INTEREST DISCLOSURE

The authors made no disclosures.

Ancillary