Research Shows Certain Metabolites Responsible for Initiating Breast and Prostate Cancer

Cancer researchers have discovered that metabolites of natural estrogens can react with deoxyribonucleic acid (DNA) to cause specific damage that initiates the series of events leading to breast, prostate and other human cancers. This understanding of a common mechanism of cancer initiation could result in cancer prevention and in better assessment of cancer risk.

The researchers will present their findings at the 81st annual meeting of the Southwestern and Rocky Mountain Division of the American Association for the Advancement of Science (SWARM-AAAS) on Friday, April 7, at the University of Tulsa, in Tulsa, Okla.

The symposium " "Catechol Estrogen Quinones as Initiators of Breast and other Human Cancers" " will be led by Drs. Ryszard Jankowiak of the Department of Chemistry, Kansas State University, and Ercole Cavalieri of the Eppley Cancer Institute, University of Nebraska Medical Center.

"We have a novel approach to cancer. We know the initiating step," said Dr. Cavalieri. "We think prevention of cancer is a problem we can solve by eliminating this initiating step. Estrogens can induce cancer when natural mechanisms of protection do not work properly in our body, and the estrogen quinones are able to react with DNA. In fact, if these protections are insufficient, due to genetic, lifestyle or environmental influences, then cancer can result."

"Now that we have the basic knowledge about a unifying mechanism of cancer initiation, we have a greater sense of urgency to assess people at risk and, at the same time, begin prevention by using specific natural compounds."

Dr. Cavalieri will discuss a unifying mechanism in the initiation of cancer. He will describe how the catechol estrogen quinones react with DNA to produce specific mutations that may trigger breast, prostate and other human cancers and show how the results of recent studies give rise to targets for preventing the disease.

"We have known about these catechol estrogen quinones for a long time, through many different studies that we have done, but our most recent results have been quite decisive," said Dr. Eleanor Rogan of the University of Nebraska Medical Center. "It's very big news. From here, we will use the information to ultimately try to prevent breast and prostate cancer."

Other presenters at the symposium and their topics include:

• Dr. Paola Muti, an epidemiologist from the Italian National Cancer Institute-Rome, the epidemiological evidence on the role of estrogens and androgens in breast cancer development;

• Dr. Rogan, University of Nebraska Medical Center, the metabolism of estrogens to reactive forms in the human breast and the differences between women who have breast cancer and those who do not. This research identifies biomarkers that could be used for early detection of cancer risk;

• Dr. Jankowiak, Kansas State University, biomonitoring techniques he has developed for assessing breast and prostate cancer risk;

• Drs. Dhrubajyoti Chakravarti, University of Nebraska Medical Center, and Joseph Guttenplan, College of Dentistry, New York University, how estrogen metabolites induce mutations, which are key events in initiating cancer;

• Drs. Jose Russo, Fox Chase Cancer Center, and Thomas Sutter, Feinstone Center for Genomic Research, University of Memphis, the role of estrogens in human breast cancer, as demonstrated in cultured human breast cells, and how mutations accumulate during estrogen-induced transformation of breast cells to cancer cells.