The Hutchinson Center has received more than $18 million from the National Cancer Institute to help lead and coordinate a nationwide research effort to better understand the link between obesity and cancer.
The ultimate goal of the five-year, $54 million initiative, which will involve a diverse team of researchers from across the United States, is to avoid an increase in obesity-related cancer deaths in the 21st century similar to the death toll exacted by tobacco in the 20th century. The Hutchinson Center is one of four research centers to receive funding for the Transdisciplinary Research on Energetics and Cancer, or TREC, initiative. The Center also serves as the coordinating hub for the effort.
The principal investigator of the Seattle-based TREC center is Dr. Anne McTiernan, epidemiologist and internist in the Public Health Sciences Division. McTiernan's research focuses on identifying ways to prevent new or recurrent breast cancer and colorectal cancer with a particular focus on physical activity and exercise.
"We know there's an association between obesity, sedentary behavior and increased risk of certain cancers, such as colon and breast — that's been shown for some time. In fact, the American Cancer Society estimates that about 30 percent of cancer deaths are due to poor nutrition, excess weight and lack of exercise. Now we're trying to understand the link between cancer and obesity at a more fundamental, mechanistic level," said McTiernan who is also director of the Prevention Center. The Prevention Center is a unique clinical-research facility, located in the Arnold Building, where study participants work out in a state-of-the-art exercise laboratory or eat meals prepared in a nutritional-research kitchen. It is the only center of its kind in the United States that focuses exclusively on cancer-prevention research, McTiernan said.
The Hutchinson Center's success in conducting studies that aim to understand the interplay of nutrition, physical activity and diet on cancer prevention is one of the key factors that led to its selection as a TREC center, McTiernan said.
"A lot of our researchers are already interested in the association between obesity and cancer. We have a track record in this area. Another strength that positioned the Hutchinson Center to receive this highly competitive grant is that we have a history of close collaboration between our public-health scientists, who focus on understanding the roles of lifestyle and environment in cancer development, and our basic scientists, who conduct fundamental research to discover the biological mechanisms that underlie the causes of cancer and other diseases," she said.
The principal investigator of the initiative's coordinating center is Dr. Mark Thornquist, a biostatistician and senior staff scientist in the Public Health Sciences Division. Under his direction the coordinating center will support communication, information dissemination, data sharing and collaboration among the TREC centers and with the NCI.
"The idea behind TREC was to create a consortium of researchers collaborating on studies to make scientific progress faster than four separate centers going their own way. The coordinating center will help with that," Thornquist said.
The other TREC centers are based at Case Western Reserve University, the University of Minnesota and University of Southern California.
The research network will encompass projects ranging from the biology and genetics of energy balance and energetics (the flow and transformation of energy through living systems) to the behavioral, sociocultural and environmental influences on nutrition, physical activity and weight.
The research to be conducted through the Hutchinson Center-based TREC center will be structured around five projects:
The five projects
Project one will test the effects of excessive amounts of glucose, or sugar, on cell growth and programmed cell death, or apoptosis. The rationale behind this project is that people with diabetes, who have high circulating levels of blood sugar and insulin, are also at increased risk for cancer. This laboratory study will test the effects of glucose on two kinds of cells: endothelial tissue (which lines the blood vessels) and epithelial tissue (which lines the glands and organs). Endothelial tissue is relevant to cancer because overgrowth of blood vessels is what feeds tumors. Epithelial tissue is relevant to cancer because most common cancers arise in the epithelial cells. Dr. David Hockenbery, Clinical Research Division, will lead this project in collaboration with endocrinologists and diabetes experts from the University of Washington School of Medicine.
Project two will test the effect of various interventions — from moderate calorie restriction to physical activity to a combination of the two — on biomarkers of cancer development in rodents. Such biological signposts could include high glucose levels, markers of inflammation or oxidative damage, or changes in the expression of certain proteins or genes. Dr. Henry J. Thompson, director of the Cancer Prevention Laboratory at Colorado State University, will lead this project in collaboration with other CSU investigators.
High vs. low-glycemic diets
Project three will be a controlled-feeding study in people — both normal weight and obese — to test the effects of a high-glycemic diet versus a low-glycemic diet on blood markers related to both obesity and cancer risk. Study participants will receive all of their meals at the Hutchinson Center's Human Nutrition Laboratory. High-glycemic diets, characterized by the consumption of large amounts of sugar and refined carbohydrates such as white flour and sweetened beverages, cause sugars to be absorbed rapidly, which in turn spikes insulin levels and promotes the storage of fat. Low-glycemic diets are characterized by the intake of foods that are absorbed more slowly and thus keep blood-glucose and insulin levels steady. Examples of low-glycemic foods include green, leafy vegetables, fish and other lean protein sources, and unrefined carbohydrates such as whole grains. Hutchinson Center Public Health Sciences investigators Drs. Marian Neuhouser, and Johanna Lampe, will co-lead this project in collaboration with colleagues at the Hutchinson Center, UW and McGill University.
Project four will enhance an existing Hutchinson Center study that is looking at the effect of a yearlong exercise program, a yearlong reduced-calorie diet or a combination of the two on biomarkers of cancer development in humans. The study, which already is tracking hormone levels associated with increased risk, will now also track markers of inflammation as well as DNA damage and DNA-repair capacity. DNA repair is an essential mechanism for protecting cells from becoming cancerous. The Seattle TREC center's principal investigator, McTiernan, will co-lead this project along with Dr. Cornelia (Neli) Ulrich, Public Health Sciences Division. Collaborating researchers will include those from the Hutchinson Center and UW.
Worksite diet intervention
Project five will adapt and test the effectiveness of an obesity-prevention project designed especially for the worksite. The two-year intervention will provide employees with the skills needed to make behavioral changes to increase physical activity and reduce food intake. In partnership with about 30 small businesses in the Seattle area, the community randomized trial will aim to raise awareness, enhance motivation and support newly adopted skills among employees to help create a working environment that is conducive to promoting better food choices and increasing physical activity. Dr. Shirley A.A. Beresford, Public Health Sciences Division, will lead this project in collaboration with researchers from UW and the Hutchinson Center.
For more information about the TREC initiative, please visit www.cancercontrol.cancer.gov/TREC/.