"We want our patients to know that we have no evidence suggesting that eating beef in any amount is dangerous," says Dr. William Farrar, a breast cancer specialist at the Arthur G. James Cancer Hospital and Richard J. Solove Research Institute and a co-leader of the study. "But we are very interested in discovering any relationship between residual zeranol and enhanced estrogenic activity in the breast. There is a lot to sort out here; this is just the first step."
Zeranol is commonly used throughout the cattle, veal and lamb industry in the United States. It is produced from the mold of a fungus often found in cereal and animal feed, and manufactured as a pellet that can be implanted under the skin of an animal's ear. Cattle growers use zeranol to help fatten the animals more quickly, create a higher lean-to-fat ratio and to develop meat with more flavor. Although zeranol has been found to be biologically active in stimulating breast cancer cell growth, the Food and Drug Administration says it is safe to use in tiny amounts in young cattle and lambs.
It is a practice that concerns Dr. Young C. Lin, a veterinarian in The Ohio State University Comprehensive Cancer Center and a co-leader of the study. Lin points out that zeranol, although a synthetic non-steroidal agent, acts like estrogen in the body. He says early laboratory studies suggest that zeranol, like estrogen, stimulates estrogen-modulated genes that can affect the growth of human breast cancer cells.
"We think this may be important, because some studies suggest that the more unopposed estrogen a woman is exposed to over her lifetime, the greater her chances of developing breast cancer," says Lin.
Lin says the key question is, does long-term, low-level exposure to zeranol add to that risk, or not? "We have examined the impact of zeranol on the breast tissue of rats – and on human breast cancer cells, as well," says Lin. "Our research shows that even in very small amounts – levels 30 times lower than FDA approved limits, zeranol seems to enhance the effects of estrogen." Still, he says it is too soon to call beef products containing zeranol a potential environmental risk. That's because what happens to cells in the highly controlled setting of a laboratory might not happen in the more naturally complex setting of the human body.
Lin and Farrar will be examining both normal and cancerous breast tissue taken from patients at The James who undergo biopsy or surgical breast reduction. Volunteers will be asked to complete a questionnaire on beef consumption, and the patients will be classified according to the amount of beef they consume. Researchers will take blood and urine samples to measure any residual zeranol against the activity of several biomarkers believed to be active in the development of breast cancer ( PTPã, KGF, PR, pS2 and cyclin D1). The biological activity of the zeranol will also be measured by the degree of cell proliferation and alteration of estrogen-responsive gene mRNA levels.
Lin and colleagues in veterinary colleges in four other universities across the country will simultaneously be collecting testing random samples of supermarket-bought beef to gauge the presence and amount of zeranol residue in commercially available products. Partner institutions include the University of Minnesota, Texas A & M, Cornell University and the University of California at Davis.
Lin says the purpose of the study is not to challenge the legality of current regulations on the usage of zeranol in food animals, but rather to offer information that could be useful to regulatory agencies in decisions about the use of growth promoters used in beef destined for human consumption.
"We hope this study will permit an evaluation of the validity of the hypothesized link between long-term, low-level dietary exposure to zeranol in beef and adverse health effects, specifically with respect to breast cancer and other estrogen-sensitive disorders," says Lin. "It is an issue that we are finally ready to address."
The study is supported by a three-year, $555,000 grant from the National Cancer Institute.