Breast-Cancer Risk, Plant-Based Estrogens and Genetic Variations in Their Breakdown to be Studied by UB Researchers

BUFFALO, N.Y. -- The role of plant-based estrogens in modifying breast-cancer risk is the subject of a five-year research study and intervention to be conducted by nutritional epidemiologists at the University at Buffalo.

The research will be funded by a $569,896 Research Career Development Award from the National Cancer Institute to Susan McCann, Ph.D., research assistant professor of social and preventive medicine in UB's School of Medicine and Biomedical Sciences.

McCann's research will focus on one class of phytoestrogens -- plant compounds with estrogen-like activity -- called lignans, which are found in the cell walls of fruits, vegetables, whole grains, berries, seeds and nuts. They are the most abundant source of plant-based estrogens in the typical American diet, and flaxseed contains the highest concentration of lignans.

Plant lignans from flaxseed have been shown to modify urinary excretion of two estrogen metabolites that have been associated with breast-cancer risk, McCann said. Moreover, epidemiologic studies suggest that cancer risk is lower among populations with higher intakes of lignans (measured by the amount excreted in the urine), she noted, but no studies to date have assessed the association between breast-cancer risk and actual dietary intake of lignans.

There also is evidence that a woman's genetic makeup may affect both the quantity of phytoestrogens that are used by the body and the way estrogens are broken down, or metabolized. The metabolic process determines the ratio of weak estrogen metabolites (thought to lower the risk of breast cancer) to strong (thought to increase the risk).

McCann and colleagues will investigate the influence of two specific genes associated with breast-cancer risk on lignan metabolism in a bank of blood samples collected from breast-cancer patients and controls, and compare lignan intake in the two groups, based on dietary records provided by participants.

In addition, they will conduct a dietary intervention, using flaxseed, to assess the effect of phytoestrogen intake on estrogen levels in healthy women, and to compare the effect of genetic variation on the effect that lignans have on estrogen levels.

Approximately 300 postmenopausal women who are not taking hormones or natural hormone supplements will be recruited for the intervention. Participants will provide blood and urine samples at the start of the study, consume about one tablespoon of ground flaxseed with their regular diet for seven days, and then provide another set of blood and urine samples. Participants also will complete questionnaires about their health, medical and reproductive history, diet and other health habits.

McCann hypothesizes that in the analysis of the banked blood samples, high intake of lignans will be associated with a decreased risk of breast cancer, independent of other non-dietary risk factors, and that the extent of this protective effect will depend on a woman's genetic make-up.

In the intervention study, she expects to find that lignan supplementation will modify serum concentrations of certain estrogen metabolites and the ratio of weak to strong estrogen metabolites, and that this ratio also will be affected by genotype.

In the final analysis, McCann said she hopes to show that consumption of foods high in lignans can help protect women from developing breast cancer.