Understanding the Influence of Body Weight and Physical Activity on Cancer Risk and Outcomes

Numerous epidemiologic studies have linked obesity and physical inactivity with increased risks of more than a dozen types of cancer. Research also suggests that physically active cancer survivors have fewer or less-severe side effects from treatment and an improved quality of life compared with those who are inactive. Associations between exercise and reduced rates of cancer recurrence and mortality have also been reported. However, more research is needed to understand the biological mechanisms by which body weight and physical activity influence cancer risk and patient outcomes. This knowledge can then be translated into effective interventions.

Research Priority

NCI funds a wide range of research to learn how body weight and physical activity modify cancer risk and outcomes, and NCI-funded researchers use the acquired knowledge to design and test new interventions.

Understand the Effects of Weight and Physical Activity on Cancer Risk and Patient Outcomes

The biological mechanisms by which body weight and physical activity influence cancer risk and patient outcomes are not well understood. Moreover, traditional epidemiologic studies are limited in their ability to determine how strongly these factors influence cancer-related outcomes because they rely on people’s ability to accurately recall or record their weight at specific ages as well as their dietary intakes and amounts of physical activity over time. Consequently, stronger study designs, such as randomized controlled trials when feasible, and more accurate survey instruments are needed. Therefore, NCI supports research in the laboratory and the clinic to address these issues, with the goal of ultimately translating the knowledge gained into effective interventions for those at risk of cancer and for cancer survivors.

Examples of NCI-funded research in this area include:

  • The Transdisciplinary Research on Energetics and Cancer (TREC) initiative, which catalyzed research on the biological, behavioral, sociocultural, and environmental influences that affect nutrition, energy balance (the ratio of calories consumed to calories burned), body weight, physical activity, and cancer risk. TREC, which was funded in 2005 and 2010, enabled the creation of research partnerships that otherwise would not have been possible. Some TREC studies incorporated animal and human models to identify and understand the relevant biomarkers and physiological effects of exercise, sedentary behavior, diet, and, cancer. The role of sleep in obesity and energy balance was also explored.

    Two of the many research advances that have emerged from TREC are:

    • An increased understanding of how obesity influences chemotherapy effectiveness: TREC researchers at the Children’s Hospital Los Angeles and the University of Southern California developed novel preclinical models to understand the mechanisms underlying the increased risk of relapse observed among obese children with acute lymphoblastic leukemia (ALL). They determined that adipocytes (fat cells) impair the response of leukemia cells to chemotherapy in a manner that is independent of cell–cell contact. These findings have led to a clinical trial of personalized dietary and exercise interventions in children and adolescents with newly diagnosed ALL to reduce body fat and improve treatment responses.
    • A greater understanding of the potential for exercise to reduce the increased risk of breast cancer associated with delayed childbearing: Research support from TREC enabled a team of researchers from the University of Pennsylvania, Harvard University, Washington University in St. Louis, and Kaiser Permanente Northern California to develop an animal model to study the protective effects of exercise on the breast cancer risk associated with delayed childbearing. The researchers found that exercised rats had a longer time to tumor development, a smaller tumor burden, and less abnormal proliferation of breast tissue (ductal hyperplasia) than rats that had not been exercised.

Other TREC accomplishments include new statistical modeling methods, a system for coding health messages in the media, new dietary measurement tools, and databases for physical activity and sleep measures. Ongoing research is exploring whether obesity, which is a risk factor for postmenopausal breast cancer, influences immune cell populations in the breast tumor microenvironment. Ideas for another TREC renewal (i.e., TREC 3) are currently in development.

  • Weight loss, diet, and exercise interventions for cancer survivors to identify those interventions that are most effective and understand how they influence outcomes for survivors. The randomized Lifestyle, Exercise, and Nutrition (LEAN) Study highlights this type of research.

Stories of Impact

NCI supports the development of interventions aimed at improving the quality of life for survivors through diet and exercise.

Running (and Eating) Away from Cancer

Sue Wharfe was diagnosed in 2011 with stage II breast cancer. Her doctors at Yale Cancer Center, where she received treatment, referred her to a research study on nutrition and exercise for breast cancer survivors. Sue jumped at the chance to participate. She hoped it would help her to lose weight and improve her diet. “I was the type of person who would join a gym, feel good about joining, but then never go. I had good intentions but following through with them was a challenge,” she explained.

Key Takeaway

  • NCI sponsors research that will increase the understanding of how diet, body weight, and physical activity influence cancer incidence and outcomes and translate the knowledge gained into effective interventions for cancer patients, survivors, and those at risk.