Spotlight on Research at COPH – The primary questions investigated in Dr. Rogan’s laboratory are “How do estrogens start the multi-step process leading to cancer, and how could this be prevented?” Most biomedical scientists have studied estrogens in terms of their causing cancer through hormone receptor-mediated events. Instead, Dr. Rogan’s laboratory considers estrogens to be chemicals that can start the process leading to cancer by acting similarly to other chemicals we encounter in the environment—in the air we breathe, the water we drink, and the food we eat.
Everybody has estrogens in their body, although women have higher levels than do men. These estrogens are routinely metabolized, and sometimes this process can lead to forms that react with DNA, damaging it and generating cancer-causing mutations. If a person’s estrogen metabolism is balanced, few of these reactive metabolites are formed and the level of DNA damage is low. If a person’s estrogen metabolism is unbalanced, because of genetic, lifestyle, or environmental factors, more of the reactive metabolites can be present and react with DNA to form so-called “estrogen-DNA adducts,” which can generate cancer-causing mutations. These adducts are formed in various tissues in the body, diffuse out into the bloodstream, and are eventually excreted in urine.
In one of the most important areas of investigation in Dr. Rogan’s laboratory, researchers analyze the levels of 38 estrogen metabolites, estrogen conjugates, and estrogen-DNA adducts in urine samples from various populations to determine whether participants’ estrogen metabolism is unbalanced toward DNA-damaging reactive metabolites. Dr. Rogan’s research team has analyzed women at normal risk of breast cancer, high risk of breast cancer, or already diagnosed with the disease. In all of the studies they have conducted in three different populations, the women at high risk of breast cancer, as well as the women diagnosed with breast cancer, had statistically significantly higher amounts of estrogen-DNA adducts than the women at normal risk for breast cancer. These results provide evidence that the estrogen-induced DNA damage is a causative factor for breast cancer. They also suggest that the adducts could be an early biomarker for risk of developing breast cancer. Current studies in Dr. Rogan’s laboratory now focus on preventing breast cancer by rebalancing estrogen metabolism and, thus, inhibiting formation of the estrogen-DNA adducts.
Eleanor Rogan, PhD, is chair of, and a professor in, the UNMC COPH Department of Environmental, Agricultural, and Occupational Health, and a professor in the Eppley Institute for Research in Cancer and Allied Diseases University of Nebraska Medical Center.