During a trip to the grocery store, a Hispanic mother and her teenage son reach for a sleeve of corn tortillas. But, a personal shopper instructs them to choose the low-carb, whole-wheat tortillas. As they move through the store, the personal shopper offers other suggestions, usually to purchase items high in fiber and low in sugar. A few days later, the shopper provides a cooking demonstration for the mother, her son, and other Hispanic parents and their overweight teenagers. One item on the menu: a whole-wheat tortilla quesadilla stuffed with steamed veggies and jack cheese, topped with avocado and tomatoes.

This wouldn't normally be the kind of activity associated with a randomized clinical trial. But under the auspices of NCI's new Transdisciplinary Research on Energetics in Cancer (TREC) initiative, it's part of a trial to help prevent overweight Hispanic and African American teens from progressing to obesity. Led by Dr. Michael Goran and colleagues at the University of Southern California - one of four institutions awarded grants under the 5-year, $54 million initiative - the trial will test whether such nutritional counseling, with or without regular strength training, can decrease body mass index.

"We've already shown in previous work that for a very overweight population, strength training is actually a form of exercise [they] can do and succeed at pretty quickly, so it gets them hooked on the process," Dr. Goran explains.

Strength training also has been shown to have significant metabolic benefits in adults, he adds, such as improving insulin resistance and the expression of related growth factors. Both have been tapped as potential links between obesity and cancer. "We think strength training can improve metabolic health in ways that will influence risk of disease," Dr. Goran says.

The trial is indicative of the broader investigation of the link between energy balance - the combined effects of factors such as diet, physical activity, and genetics over a lifetime - and cancer risk that NCI is pursuing with the TREC initiative.

"We're looking at issues beyond just diet or exercise alone and addressing the link between energetics and cancer risk from cells to society," says Dr. Linda Nebeling, of the Behavioral Research Program in NCI's Division of Cancer Control and Population Sciences (DCCPS).

Research at the four TREC centers, she says, will test interventions, but also holistically assess how body weight, diet, exercise, environment, and other factors affect physiologic systems and intracellular pathways to see whether and how they influence carcinogenesis.

TREC also is part of an important NCI goal, stresses DCCPS director Dr. Robert Croyle.

"NCI is determined to avoid an increase in cancer deaths in the 21st century due to obesity such as the one caused by tobacco in the 20th century," he says.

The available data support that concern. Overweight and obesity are estimated to contribute to about 90,000 cancer deaths a year. Excess pounds are thought to significantly increase the risk of at least nine cancer types, including endometrial, kidney, and colon cancer. Obese men, for example, have twice the risk of developing colorectal cancer as men of normal weight. Obesity is also considered a principal culprit behind the increase in some once-rare cancers, including esophageal adenocarcinoma, which is increasing in incidence in the United States faster than any other cancer.

Obese postmenopausal women have a 50 percent higher risk of breast cancer than their nonobese counterparts, says Dr. Anne McTiernan, the principal investigator for the TREC projects being conducted through Fred Hutchison Cancer Research Center, which also serves as the coordination center for the initiative. One project will assess, in a rat model of breast cancer, how factors such as food restriction and physical activity influence the carcinogenic process. A similar project will be conducted in more than 500 postmenopausal women participating in a clinical trial funded partly through TREC.

Nearly all of the projects at the other two TREC centers - Case Western Reserve University and the University of Minnesota - will attempt to discover the biologic and physiologic mechanisms by which obesity increases cancer risk.

"There are several reasons why it is important to learn the mechanisms," Dr. McTiernan says. New insights into the mechanisms could influence recommended prevention measures, such as whether exercise alone is sufficient to reduce risk or if being lean is also required.

And learning more about the mechanisms may allow researchers to test new preventive interventions or treatments. "For example," Dr. McTiernan continues, "if we learn that insulin resistance and hyperinsulinemia explain the association between obesity, being sedentary, and cancer risk, then perhaps we could treat patients with metformin, which reduces insulin resistance, either as a chemopreventive agent or as an adjuvant treatment for cancer patients."

By Carmen Phillips