Presence of Estrogen Metabolites in Urine Predicts Cancer

Estrogens can initiate cancer when natural mechanisms of protection do not work properly in the body, allowing estrogen metabolites to react with DNA. A simple test can determine the presence of the estrogen metabolites in urine and be an indication of breast and prostate cancer risk.

Estrogen metabolites react predominantly with the first two DNA bases, adenine and guanine, to form estrogen-DNA adducts. The resulting damage generated by the reaction can give rise to mutations that eventually initiate cancer. The important estrogen-DNA adducts spontaneously fall out of the DNA, leaving behind gaps that generate cancer-initiating mutations. The estrogen-DNA adducts eventually make their way out of cells and are excreted in urine.

The screening test developed by scientists analyzes estrogen metabolite profiles in humans and simultaneously associate the profile with risk of getting breast cancer. A one-ounce sample of urine is tested using tandem mass spectrometry, which analyzes about 40 estrogen-related compounds, including estrogen-DNA adducts.

Scientists analyzed estrogen-DNA from 46 women with normal risk for breast cancer, 12 women at high risk of developing breast cancer, and 17 women diagnosed with breast cancer. They found women at high risk of breast cancer and the women with breast cancer had significantly higher levels of the estrogen-DNA adducts in their urine samples, while the women with normal risk for breast cancer had low levels.

The University of Nebraska Medical Center (UNMC; Omaha, NE, USA) team stated that there is a single initiating step in cancer development and that cancer can be assessed, prevented, and detected by understanding this common mechanism.

Eleanor Rogan, Ph.D., who took part in the study, said, "We have found the first step that starts a cell down the road to becoming a cancer cell. By preventing this first step from happening, we think we can stop the development of breast or prostate cancer. The combination of an early detection test for cancer risk with administration of preventing agents should enable us to significantly reduce the number of women and men that develop breast or prostate cancer.”

"If these protections are insufficient, due to genetic, lifestyle, or environmental influences, we think cancer can result,” Dr. Cavalieri said. "Now that we have the basic knowledge about this unifying mechanism of cancer initiation, we have a greater sense of urgency to assess people at risk, and at the same time, begin studies of prevention by using specific natural compounds.”

The findings were published in the December 2008 issue of the International Journal of Cancer. The study involved investigators at the University of Nebraska Medical Center (Omaha, NE, USA), Mayo Clinic (Scottsdale, AZ, USA), and the Italian National Cancer Institute (Naples, Italy).


Related Links:
University of Nebraska Medical Center
Mayo Clinic