New Methods in Clinical Trials Lending New Insights on Diet-Cancer Connection, Expert Says

American Institute for Cancer Research
Thursday, 31 August 2000

"Biomarkers" Make Measuring Effects in Humans Easier, More Reliable than Ever

In a luncheon presentation at the 10th Annual Research Conference of the American Institute for Cancer Research (AICR), cancer researcher Cheryl Rock, Ph.D., R.D., outlined the progress of human trials investigating the diet-cancer connection. She described the many obstacles scientists must overcome to study the enormously complex human diet, and revealed how new methods and technologies are revealing the link between diet and cancer more clearly than ever before.

Rock said that researchers are now identifying biomarkers - measurable biological factors that can be used to precisely track and measure dietary change without having to rely on the self-reported food intakes of clinical trial participants. This is important because in the past, trial subjects have been documented underreporting the amount and type of food they eat by as much as 30 percent.

One example of a biomarker is the recent discovery that a person's fruit and vegetable intake can be reliably determined by examining the level of carotenoids in his or her blood. But the ability to verify dietary data is only one advantage of using biomarkers as measures in clinical studies. They also help scientists design new research approaches that reflect the real-world influences of diet upon the human body.

Other types of biomarkers, for example, are used to measure "oxidative stress" - the kind of genetic damage believed to be central to the cancer process. Still other biomarkers are used in human studies to "stand-in" for the cancer process itself, which allows researchers to safely and ethically measure the effects of diet upon cancer risk.

Breast cancer patients in some clinical trials are watched for increased DNA replication in their mammary cells, a condition that often signals a pre-cancerous state. Many scientists, however, do not believe a change of this nature to be a reliable surrogate for the cancer process, and the search for a universally accepted "stand-in" for the cancer process continues.

Dr. Rock spotlighted two dietary intervention studies that use biomarkers to measure both the extent of dietary change and the effect of this change upon cancer risk.

The Women's Healthy Eating and Living (WHEL) Study is testing whether a high-vegetable, low-fat diet can reduce risk for the recurrence of breast cancer. The multi-center Study involved 3,000 breast cancer survivors, aged 18 to 70, in California, Oregon, Arizona and Texas.

Designed as an eight-year dietary intervention, the WHEL Study will complete enrollment of study participants within the next few months. The anticipated study end date is 2004. Preliminary data show that women can make and maintain major changes in their diets, which may help to alter their risk for recurrence of cancer.

The Cancer Prevention for Women (CAPRE) Study is testing whether a diet high in vegetables and fruit can increase the regression rate of cervical dysplasia. Cervical dysplasia is diagnosed as an abnormal Pap smear, and the results of many epidemiological studies suggest that changing the diet to include more vegetables and fruits may help the body to overcome the condition and cause the cervical tissue to normalize. Young women with very busy lives are the focus of this study, and results to date show that individualized and practical dietary guidance can result in big changes in their diets.

Clinical Trials Are Latest Step in Long Series of Studies

Rock said that much of the evidence linking diet to cancer risk is based on the results of so-called epidemiological studies, which compare the diets and cancer rates of groups of individuals or even whole populations. Results of these studies have consistently associated diets high in fruits, vegetables, whole grains and beans with lower risks for many cancers. But epidemiological data are only a first step, in that they can suggest associations, not pinpoint specific causal relationships.

Laboratory tests - which involve cell or tissue cultures and animal models - have so far uncovered several biological processes ("mechanisms") by which diet may reduce the risk or possibly slow the progression of cancer. Although these results may or may not correspond to human biology, such findings do strongly support the mounting evidence for a diet-cancer link.

To date, most of the clinical human trials that have tested the influence of diet upon cancer risk have involved single nutrients. Dr. Rock believes the negative results of these tests are only to be expected, as "reductionist" approaches fail to allow for the interaction of substances within foods.

"There is a shift underway in the study of diet," said Dr. Rock, "one that applies new methods and measures to study the effects of overall dietary patterns on cancer risk."

Dr. Rock is a Professor at the University of California at San Diego's Cancer Prevention and Control Program and the Department of Family and Preventive Medicine. She has published widely on nutrition, dietary change, and disease prevention.

For more information, or to contact American Institute for Cancer Research, see their website at: www.aicr.org