# Presentation: 343157

## Transdisciplinary Research on Energetics and Cancer

**Linda Nebeling, PhD, MPH, RD**
**Rachel Ballard-Barbash, M.D.**
**National Cancer Institute**
**National Institutes of Health**
**U.S. Department of Health and Human Services**
**August 16, 2004**

## Relationship between Diet, Energy Balance, Obesity and Cancer Risk 

**Relationship between Diet, Energy Balance, Obesity and Cancer Risk**** **

**Physical Activity**

**Weight**

**Notes:**
Physical activity, combined with a balanced diet, has numerous mental and physical health benefits, including the reduction in the risks of premature mortality, cardiovascular disease, hypertension, diabetes, depression, osteoporosis and cancer.
Important health benefits include a reduced risk of colon, breast and endometrial cancer.

In addition, physical activity is an important complement to dietary management for the avoidance weight gain and weight maintenance after intentional weight loss.

## Energy Balance, Energetics and CancerStatus of the Evidence

**Extensive epidemiologic research on obesity and cancer association and limited but growing evidence on physical activity and cancer**
**IARC report -- *****Weight control, physical activity and cancer -- ***_***[http://www.iarc.fr/](http://www.iarc.fr/)***__*** ***_
**Extensive epidemiologic research on diet and cancer, very little examining role of energy balance, energetics**** **
**Clinical metabolic and basic research on underlying mechanisms, most often with changes in one factor at a time**
**Limited intervention research on weight control, physical activity on cancer prognosis and quality of life**** **
**No clinical trials on whether weight control or physical activity reduce cancer incidence**

## Obesity and Cancer Incidence

**Incidence and Prevalence**
**Increased risk:**** **
**	****Endometrial, Breast (Post-menopause), Colon, Kidney **
**	****(Renal Cell), Esophagus (Adeno), Thyroid**
**Decreased risk: **
**	****Breast (Pre-menopause), Lung, Head and Neck**
**Inadequate evidence to assess: **
**	****Cervical, Gallbladder, Ovarian, Pancreas, Testis**
**No association:**** Prostate Cancer**** **
**2002 IARC report estimated obesity and physical inactivity accounted for ****25 to 30%**** of these cancers:**
**Colon, breast (postmenopausal), endometrial, renal cell, and esophagus**

**Notes:**
The international Agency for Research on Cancer IRAC has estimated that at least 11 to 15 percent of breast and colorectal cancers may be attributable to inadequate physical activity IARC, 2002) 
Overall, sedentary lifestyles, combined with poor dietary choices, have been lined to 25-30 percent of deaths from Cancer.
Lifestyle choices involving physical activity and diet are reversible.  Evidence has shown that increasing one’s level of physical activity can reduce the risk of mortality.

High levels of physical activity may reduce the risk of colon cancer by as much as 50%.
Part of the challenges in the diet and physical activity relationship is the challenges in identifying standard measures of physical activity or dietary assessment.  

Research by I-Ming Lee at Harvard has suggested that those who maintain high levels of physical activity throughout life appear to have the greatest disease risk reduction (Lee , 1991)

Mechanisms explaining the effects of physical activity are still under research, but a possible cause is the reduction in fecal transit time in subjects more physically active, along with a reduction in circulating levels of insulin, a growth factor for colonic epithelial cells. 

##  Transdisciplinary Conceptual Model 

-  Energy Balance,
- Obesity,
- Weight,
- Energetics

- Physiological*
- Factors

- Behavioral*
- Factors

- Genetic
- Factors

- Socio-cultural
- Factors

- Environmental
- Factors

- Institutional/
- Policy Factors

- Cancer

** **Macro-Level Factors       Micro-Level Factors
-  	  (Contextual)	        (Individual)

- *Physiological and Behavioral Factors contribute to the additional factors of Personality (e.g., extraversion), Psychological Factors (e.g., stress), and Cognitive Factors (e.g., beliefs)

**Notes:**

*Physiological and Behavioral Factors contribute to the additional factors of Personality (e.g., extraversion), Psychological Factors (e.g., stress), and Cognitive Factors (e.g., beliefs)

Note: The model presented above is not comprehensive, but represents a general conceptual framework illustrating the major factors that may contribute to obesity/weight/energy balance within the context of cancer.  The specific physiological mechanisms responsible for the influence of obesity/weight/energy balance on cancer are not delineated in this model.  Moreover, the specific physiological, behaviors, psychological, social, environmental, and institutional mechanisms that may influence the development of obesity/weight gain/energy imbalance are not delineated. 

## What is “Transdisciplinary?”

**Development and application of a shared, integrative conceptual framework based on discipline-specific theories, concepts, and methods**
**Instead of working in parallel, investigators collaborate across levels of analysis and intervention to develop a comprehensive understanding of energy balance and cancer**

## Two Major Challenges

**Enhancing understanding of the mechanisms underlying the association between energy balance and carcinogenesis across the cancer continuum and the life cycle**** **
**Developing effective approaches with broad population impact at the social-environmental and policy level for the prevention and control of obesity**
**Focusing on children and adults during critical periods for excessive weight gain**

## How does a Transdisciplinary Focus Address the Gaps?

**Critical mass of investigators**
**Transdisciplinary collaboration within and across research centers**
**Unique context for training**
**Shared resources for greater efficiency**

## Gaps: Mechanisms

**Very limited research on the interaction of diet, physical activity and weight and cancer outcomes**** **
**Need to examine genetic/lifestyle interactions**
**Genomics and proteomics**
**Use of animal models that allow examination of variation in effect over the life course**

## Barriers to Progress

**Research is limited on the intersection of diet, weight and physical activity**
**Most research is not transdisciplinary**** **
**Need to engage research disciplines not previously playing a large role in biomedical research**
**Urban planning, transportation, communications**** **
**Need to bridge multiple disciplines to identify individual and population level solutions to a complex health problem**

## Research at the Social-Environmental and Systems Level 

**Systems/Policy changes needed to counter the epidemic of obesity, inactivity and poor diet**** **
**Major focus for efforts to prevent obesity, especially among children and young adults and minorities at risk**** **
**Range from policies for schools, worksites, cities to reimbursement for health care interventions**

## Examples of Research Areas

**Define the role of specific diet and physical activity regimens on insulin resistance and the glucorticoid axis and interactions with sex steroids on genetic and phenotypic expression of cancer**
**Examples of disciplines involved: basic science, genetics, proteomics,epidemiology, endocrinology, clinical interventions, bioinformatics, behavioral sciences, exercise physiology, nutrition**

## Examples of Research Areas

**Develop effective population level interventions for the prevention and control of obesity with a focus on children**
**Examples of disciplines involved: sociology, transportation, urban planning, public health policy, communication, education, behavioral sciences, economics, landscape architecture**

## Transdisciplinary Research on Energetics and Cancer (TREC)

**U54 Mechanism **
**Maximum of $2.5 million per year total costs ($1.5 direct) for each center award (5-7 awards)**
**Coordinating Center (U01) of $1 million per year total costs ($.6 direct) for one award**
**Maximum of 5 years**