NCI Initiative Focuses on Obesity-Cancer Link
The initiative's multidisciplinary approach may help unravel the complex connection
Long known to be a risk for many health problems, the combination of obesity, poor diet, and lack of exercise is becoming increasingly linked to certain cancers. Research in both animal models and epidemiology, for example, has shown that higher body mass index (BMI) ratings raise the risk of breast cancer and that obesity is associated with an increased risk of cancers of the endometrium, gastrointestinal tract, kidney, thyroid, and prostate.
In an effort to better understand these associations and advance research in the field, the National Cancer Institute (NCI) established the Transdisciplinary Research on Energetics and Cancer (TREC) initiative in 2005. The initiative takes a broad view of the obesity problem as it relates to cancer, funding research from “cells to society” at 4 research centers in addition to a coordinating center. The second round of funding, with 4 new centers, began in the summer of 2011.
Broad Array of Researchers
The impetus for launching the program was based on developing a better understanding of the connections between obesity lifestyle risk factors and cancer. “With improved methodologies, we were able to be more precise about how we evaluate diet and physical activity measures as well as how we understand cellular mechanisms,” says Linda Nebeling, PhD, TREC scientific program director and chief of the NCI Health Behaviors Research Branch. “We also previously had run several transdisciplinary initiatives in other areas, including tobacco use and population health and health disparities, which brought together a broader array of scientists.”
Equipped with this background, NCI leaders believed the time was right to launch TREC. The initiative's main goal is to bring together researchers from multiple disciplines to better understand the complex connections between obesity and cancer. Among the many types of scientists who have been brought together to collaborate are specialists in behavior science, physiology and metabolism, sociology, communications, geography, psychology, kinesiology, nutrition, biostatistics, biochemistry, and molecular biology.
In the first 5 years, TREC funded 14 research projects and 119 pilot projects that delved into the basic biology and genetics of behavioral, sociocultural, and environmental influences on nutrition, physical activity, weight, energy balance, energetics, and cancer risk.
Among some highlighted findings:
A shorter duration of sleep significantly increases the risk of colorectal adenomas, suggesting sleep duration as a novel risk factor for colorectal neoplasia.1
Young adults often purchase and eat foods outside of commonly used geographic information system-generated buffers around their homes, suggesting the need for a broader understanding of young adult food environments.2
In a mouse study, the obesity-resistant and reducedfood intake phenotypes investigated were transmitted through the paternal lineage, but not the maternal lineage, with equal strength for at least 2 generations, raising the possibility that transgenerational genetic effects contribute to current metabolic conditions.3
In another mouse study, adipocytes prevented chemo-therapy-induced apoptosis, which was associated with the increased expression of the 2 prosurvival signals, Bcl-2 and Pim-2. These findings highlight the role of the adipocyte in fostering leukemia chemotherapy resistance and may help explain the 50% increased rate of leukemia recurrence noted in obese children and adults.4
Increased Access to Results
This next round of TREC includes $45 million for 4 new centers and the existing coordinating center. The initiative continues to involve multiple disciplines and expand into new areas of research such as cancer survivorship, child-hood obesity, genomics, and environmental aspects of obesity that include the use of tools such as geospatial analysis. In total, 16 research projects have been funded, while new pilot projects are under development.
“This mechanism enables NCI to become a scientific partner with all the centers, and we develop working groups on a variety of questions,” says Dr. Nebeling. She adds that this phase of the initiative will focus on larger, systematic model effects and will use certain cancers as models for other cancers.
“Another goal of TREC is to research policy and methods that can be used to modify behaviors,” says Mark Thornquist, PhD, principal investigator of the TREC coordinating center, which is located at the Fred Hutchinson Cancer Research Center in Seattle, Washington. “We don't know what interventions are effective in targeting diet and physical activities because it's very difficult to get habits to change. Diet is more than what you eat–it's a behavior.”
The coordinating center is charged with supporting all communication and collaboration among the centers as well as providing data management, bioinformatics, dissemination of results, training, and evaluation. “This round of funding is more focused on figuring out how to make information from the projects more widely available to outside investigators,” says Dr. Thornquist.
The new TREC centers include:
Harvard University in Boston, Massachusetts, which is focusing on biological mechanisms linking obesity and cancer throughout the lifespan and translating that knowledge into behavioral interventions targeting children, minorities, and cancer survivors.
University of California at San Diego, which is researching mechanisms linking obesity with breast cancer risk. They also are investigating obesity and lifestyle factors related to insulin resistance and inflammation using mouse models, clinical trials, and wireless and networked technologies in the community.
University of Pennsylvania in Philadelphia, which is examining the association between energy balance and breast cancer recurrence as well as persistent adverse treatment effects. In addition, researchers are exploring the impact of exercise and weight-control interventions in cancer survivors through cost-effectiveness analysis.
Washington University in St. Louis, Missouri, which is using multilevel and multigenerational approaches to understand how preconception diet, along with nutrition and built environment policies, affect inactivity. The researchers also are studying how physical activity and energy balance influence body weight and carcinogenesis across the lifespan.
A Collaborative Effort
The association between obesity and cancer is complex, and the TREC investigators are addressing it on a variety of fronts. At Washington University, for example, Kelly Moley, MD, is using a mouse model to examine the effect of a maternal high-fat diet on prostate cancer development in male offspring. The offspring will be followed for more than 1 generation. Two additional researchers there, Kate Wolin, ScD, and Adam Kibel, MD, will evaluate the role of physical activity and obesity in urinary and sexual function after prostatectomy. That project is an example of combining expertise from 2 different disciplines (Dr. Wolin in epidemiology and Dr. Kibel in surgery) to tackle an important question, says Sarah Gehlert, PhD, coinvestigator for the Washington University TREC center.
Still another Washington University project examines the effect of existing worksite policies and environments on energy balance and obesity. Some sites in the study will have many supportive policies such as an onsite gym, healthy foods, and educational materials, whereas others will have no “healthy” programs. Researchers will determine the most effective policies for both workplaces and communities and then disseminate the results to employers, local governments, and others.
The center's final study uses a systems modeling laboratory and computer simulation to develop a model of obesity and non-Hodgkin lymphoma. Researchers will attempt to understand the role that social determinants play in the link between obesity and cancer at the population level across the lifespan.
Learning about the science of others' disciplines is vital to the TREC initiative. “We've had 2 retreats so far, and each time it advances everybody's thinking,” says Dr. Gehlert. She gives the example of sharing with Dr. Moley that if you tell pregnant mothers to change their diets because they might cause their children to be overweight, they would be unlikely to change, but if you tell them their children might experience academic difficulties, they would be more inclined to do so. Hearing that information led Dr. Moley to consider adjusting some of her research. At the same time, the center's policy researchers are becoming more familiarized with the basic biology underlying various behaviors and outcomes.
Meeting with scientists from all the involved disciplines “puts energy into what you do to think more broadly,” Dr. Gehlert says. “It not only makes the work more exciting, but it encourages you to ramp up your own research.”