Optimizing Energy Balance to Reduce the Cancer Burden

Goal

Understand the causes of adverse patterns of weight, physical activity, and diet; define their contributions to cancer; and apply this knowledge to cancer prevention and control.

Introduction

The term "energy balance" refers to the integrated effects of diet, physical activity, and genetics on growth and body weight over an individual's lifetime. Scientists are increasingly aware of the importance of understanding the effects of energy balance on the development and progression of cancer and on cancer patients' quality of life after treatment.

At a time when almost two-thirds of the U. S. population is considered overweight or obese, international teams of scientists have assembled compelling evidence that as overweight and obesity increase, and physical activity decreases, the risk of developing many cancers rises:

• A comprehensive 2002 international review by the International Agency for Research on Cancer (IARC) summarized, for the first time, the compelling evidence that prevention of obesity reduces risk for many of the most common cancers such as colon, postmenopausal breast, uterine, and renal cell cancers, and that physical activity reduces risk for colon and breast cancers.
• The IARC report further estimated that 20 percent to 30 percent of some of the most common cancers in the United States, including breast, prostate, colon, kidney, and uterine cancers, may be related to overweight and/or physical inactivity.
• Other international findings indicate that physically active people have a 50 percent decreased risk of colon cancer.
• Evidence from a large cancer cohort study based on results from almost 1 million subjects argues that overweight and obesity in our Nation account for 14 percent of deaths from cancer in men and 20 percent in women.

A 2003 Institute of Medicine (IOM) report on cancer prevention and control assigns top priority to the development of a national strategy to prevent obesity and sedentary behavior, second only to efforts to curtail tobacco use. However, because proven, evidence-based methods of preventing these unhealthful conditions are lacking, we must begin by learning more about energy balance through comprehensive and effective research.

Clearly, now is the time for NCI to apply increased resources to research and intervention development that addresses energy balance and carcinogenesis for cancer prevention and control. New efforts in this area will complement and extend existing efforts by NIH and other Federal and private partners. With the rapid rise of obesity and sedentary lifestyles among children and youth, research must focus particular attention on this vulnerable population.

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Progress in Pursuit of Our Goal

NCI is committed to providing leadership to advance energy balance research through targeted investments, as well as through collaborations with public and private partners. NCI-supported research has revealed a number of important findings, including:

• Mechanisms by which diet, weight, and physical activity affect carcinogenesis.
• New methods for quantifying key health behaviors and their consequences.
• Innovative means for evaluating progress through national and regional health monitoring.

Even so, much remains to be learned about research methods, mechanisms of energy balance-related cancer morbidity and mortality, and the interplay of multiple energy-balance risk factors on cancer development.

Discovery

• Improving Research Methods
• Discovering Mechanisms
• Evaluating Multiple Risk Factors
• Understanding the Role of Physical Activity and Diet

Development

• Learning How to Change Behaviors
• Developing Health Monitoring Systems

Discovery

Improving Research Methods

NCI and its partners are improving diet and physical activity measures, including both self-reported and objective measures. Recent research includes the following:

• The Observing Protein and Energy Nutrition (OPEN) study, the largest of its kind, used biomarkers of dietary intake to assess the accuracy of dietary assessment methods commonly used in epidemiology, intervention, and surveillance research. The investigators found that self-reported intake measures used in many studies are not sufficiently accurate. Further research will examine whether these findings are true for diverse populations, for other dietary-report or physical activity instruments, and across varying nutrients and food groups, as well as how the measurement inaccuracies may affect ongoing prospective cohort studies.

• The NIH Behavioral Change Consortium studies, cofunded by NCI, provided a setting for researchers to validate NCI-developed short screening questionnaires to assess changes in intake of fats, fruits, and vegetables. This and other research highlighted a need for innovation in measurement of diet and physical activity. In response, NCI is sponsoring the first NIH-wide program to improve diet and physical activity assessment methodology across culturally diverse populations.

Discovering Mechanisms

Researchers are discovering the mechanisms by which sedentary behavior or insufficient amounts of physical activity, poor diet, and overweight or obesity increase an individual's risk for cancer from infancy through adult life. Investigative teams employ resources ranging from preclinical models to epidemiologic studies and clinical interventions. Findings include the following:

• Investigators discovered that leptin, a hormone that tends to be elevated in obese people, provides researchers with a more precise means of studying the relationship between estimated total body fat and cancer. For example, using leptin measurements, researchers were able to establish a link between total body fat and the risk of developing prostate cancer. Prior studies using measurements such as weight or body mass had been unable to make this association.
• Preclinical investigators using Mouse Models of Human Cancers Consortium (MMHCC) mice discovered that increased activity was more protective in male than female mice.
• Another team of investigators found that postmenopausal women participating in a 1-year physical activity intervention program experienced beneficial changes in total body fat, body fat distribution, and levels of circulating hormones. This discovery may lead to interventions to prevent hormone-dependent cancers, such as breast and endometrial cancers.

Intramural and extramural clinical researchers are exploring the ways that chemopreventive agents, diet, weight, and physical activity affect cancer development in humans.

Evaluating Multiple Risk Factors

Researchers evaluating multiple risk factors have found that the effect of women's body mass index on colon cancer risk changes, depending on estrogen exposure. Examples of other findings include:

• Breast density measurements, a marker for breast cancer risk, can be used to evaluate interventions that target pathways such as estrogen or insulin metabolism to reduce breast cancer risk.
• Results from the Women's Health Initiative, which examined the effects of obesity and physical activity on postmenopausal breast cancer risk, demonstrated that being physically active is most protective among women who remain of normal weight after menopause. This protection was not observed among obese women.

Understanding the Role of Physical Activity and Diet

In the last 5 years, scientists have improved their understanding of the relationship between physical activity and cancer, leading to critical insights into strategies to reduce the incidence and burden of cancer.

Recent discoveries highlight the role genetic differences may play in individuals' capacity to exercise as well as their risk for obesity. Now scientists must incorporate genetic information into large population studies to understand how the interplay of genetics with diet, obesity, and physical activity may alter cancer risk.

Among cancer patients and survivors, anecdotal and research evidence suggests that physical activity benefits cardiopulmonary function and quality of life, reduces fatigue and depression, and improves muscular fitness. Low- to moderate-intensity regular physical activity programs may help breast cancer patients maintain functional ability and minimize weight gain. This in turn may help prevent disease recurrence and other comorbidities.

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Development

Learning How to Change Behaviors

As a first step in the development of energy balance interventions, NCI is researching key determinants of behavior change. This research has brought to light the difficulty of treating obesity once it has developed, and further reinforces the need for obesity prevention research, particularly among children and adolescents.

Although much is known about how dietary and physical activity behaviors can be changed, attempts to develop behavioral interventions to effectively increase physical activity are relatively new. Therefore, NCI:

• Is sponsoring an NIH-wide effort to accelerate research on the mechanisms of physical activity behavior change.
• Has worked with groups such as the Agency for Healthcare Research and Quality and the National Academy of Sciences to conduct research reviews, providing information to aid evidence-based intervention development for dietary and physical activity behaviors.

Developing Health Monitoring Systems

NCI supports research to develop enhanced health monitoring systems at the national and regional levels to evaluate progress in cancer control across diverse populations, including minority and underserved populations. For example:

• NCI included physical activity monitoring in the 2003 National Health and Nutrition Examination Survey (NHANES) to address discrepancies discovered in previous studies between reported and objective measurements of physical activity. Researchers will compare reported physical activity levels to measurements such as body composition and cardiovascular fitness, generating the first critically objective examination of physical activity data on a nationally representative sample. In addition, NCI-supported research has enhanced methods for evaluating usual food and nutrient intake in national populations.
• NCI-sponsored research has demonstrated that the structure of neighborhood environment, such as availability of sidewalks, may enhance walking. NCI is partnering with the Centers for Disease Control and Prevention to collect data on diet, weight, physical activity, and neighborhood environment to determine whether there is a relationship among these factors in some communities.

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Objectives and 2005 Milestones and Required Funding Increases

Discovery

Development

Discovery

Development

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People's Story: Energy In, Energy Out - A Critical Balance

I've struggled with my weight since I was about 13. I gain, I lose, I gain again. . . . I know the extra weight makes me more likely to have heart disease and diabetes, but now the scientists are saying I'm also at higher risk for many cancers. I try to eat right and exercise regularly, but it's really hard for me to build new habits.

The evidence is now clear that obesity is a significant risk factor in many cancers, including cancers of the colon, prostate, postmenopausal breast, uterine, and renal cell. It has been estimated that overweight and obesity in the United States may account for 14 percent of all cancer deaths in men and 20 percent in women, adding up to more than 94,000 deaths each year.

• In women, increased body mass also is associated with higher rates of cancers of the breast, endometrium, cervix, and ovary.
• In men, excess weight also increases stomach and prostate cancer risk.

Researchers suspect that many of the mechanisms responsible for this increased risk are systemic in nature, simultaneously increasing the risk of cancer in many parts of the body. For example:

• Overweight and inactivity have been shown to cause the body to secrete increasingly higher amounts of insulin and other growth factors.
• Cells exposed to high levels of these substances over an extended period are more prone to accelerated growth. This rapid growth increases the likelihood of random genetic mutations which, in turn, elevates the risk of cancer.

Other mechanisms related to energy balance appear to be specific to certain cancer types. For example:

• Investigators have demonstrated that exercise decreases colon cancer risk, possibly by increasing the rate at which harmful waste products move through and exit the colon.
• Epidemiologic researchers have shown that overweight or obese women, especially those who gain weight throughout adulthood, experience increased risk for breast cancer after menopause. Even moderate regular exercise may help reduce this risk by decreasing estrogen levels in the breast tissue.

Scientists have identified obesity and sedentary lifestyle as two important and modifiable risk factors for cancer. Experts believe that it is particularly important to reach children with information about healthy eating and regular exercise while their lifestyle patterns are developing and before they experience excess weight gain.

NCI is working to accelerate our understanding of the many aspects of energy balance and specific cancers and cancer in general, and to devise ways to communicate this information to all populations. Investigators are examining the relationship between cancer and the independent and combined effects of reduced energy intake (caloric restriction), various components of diet (e.g., carbohydrates, protein, fat), specific foods, micronutrients, food preparation methods, and types and intensity of physical activity.

To further this research, NCI is hoping to support more transdisciplinary research dedicated to:

• Improving our understanding of how energy balance affects risk across the cancer continuum, from causation through survival.
• Developing innovative approaches to obesity prevention, especially among children and in diverse populations.

This People's Story is an amalgam of individual experiences.

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