Breast Cancer Genetics and Relationship to Dietary Folate and Alcohol Are Focus of $2.4 Million UB Study

BUFFALO, N.Y. -- University at Buffalo epidemiologists have received a $2.4 million grant from the National Cancer Institute to conduct a four-year investigation of breast cancer, examining genetic susceptibility, tumor characteristics and dietary intake of fruits, vegetables and alcohol as they relate to breast-cancer risk.

Jo Freudenheim, Ph.D., professor of social and preventive medicine in the UB School of Public Health and Health Professions and lead investigator on the study, said the project will have several components, beginning with an investigation of genetic variation in several enzymes that may play a role in metabolic mechanisms related to breast-cancer risk.

Freudenheim is a recognized authority on the relationship between nutrition and cancer. During the past 15 years, she has conducted funded research in several areas related to diet, including studying the effects of eating fruits and vegetables and the nutrients found in those foods on several types of cancer; the effect of genetic variation on the association between diet and cancer; the relationship of alcohol consumption to risk of breast cancer and other chronic diseases, and the effects of early life exposures to cancer risk in adult life.

In this newest study, Freudenheim and colleagues will focus on enzymes related to metabolism of dietary folate, a B vitamin thought to be protective, and alcohol, which has been associated with increased risk of breast cancer. They also will investigate whether tumors of women who have low blood levels of folate or high alcohol consumption show different mutations than tumors in women who do not have these risk factors.

"There is evidence that women who have lower intakes of folate are at increased risk of breast cancer, and that high intakes of alcohol increase risk," she said. "Alcohol is known to interfere with both the absorption and the utilization of folate.

"There also is evidence that those who consume large amounts of alcohol, but also have high folate intake, are not at increased risk, leading us to think that folate may be part of the alcohol-and-breast-cancer relationship," she said. "We want to look into this relationship further."

Folate is an important player in a mechanism called one-carbon metabolism, which is involved in several significant processes, including DNA and RNA synthesis, and control of DNA expression, and might be a limiting factor in breast-cancer risk, Freudenheim noted. Sources of folate include orange juice, grains (bread, cereal and other foods using flour that is fortified with folate), green salad and other greens.

The study will involve 1,000 women who have had surgery for breast cancer and 2,000 controls who took part in an earlier UB study of lifetime alcohol exposure and breast-cancer risk, funded by the U.S. Department of Defense Breast Cancer Research Program.

"We will be examining tumor tissue from our cancer cases and looking for particular changes in the DNA in that tissue to see if, among women with low folate who got breast cancer, we do see the kinds of changes in the DNA in the tumor tissue that we might expect," said Freudenheim. "We are looking for chemical confirmation in the tissue itself of the mechanisms that have been hypothesized for the associations that we see."

Genetic information from controls will be obtained from blood samples.

"By combining information on alcohol and folate intake, genetic susceptibility and tumor characteristics, it will be possible to make clearer inferences about the role of these mechanisms in breast-cancer development," she said. "This information has potentially important public health implications."

Freudenheim acknowledged the important contributions of the women who participated in the initial study and the physicians and hospitals that cooperated in the research.

"They are all very important in moving our understanding forward," she said.

Additional investigators on the study are Paola Muti, M.D., Ph.D.; Ellen Smit, Ph.D.; Susan McCann, Ph.D., and Sharita Womack, Ph.D., all of the UB Department of Social and Preventive Medicine; Stephen Edge, M.D., of Roswell Park Cancer Institute, and Peter Shields, M.D., of Georgetown University.