Researcher wins DOD grant to find biomarkers explaining racial disparities in prostate cancer
Izabela Podgorski, Ph.D.
Izabela Podgorski, Ph.D., an assistant professor in the school’s Department of Pharmacology, won a $342,000 Early Career Investigator Health Disparity grant for her three-year project, “Biochemical and Genetic Markers in Aggressiveness and Recurrence of Prostate Cancer: Race-Specific Links to Inflammation and Insulin Resistance.”
Prostate cancer is a leading cause of death for men in the United States. Prostate cancer deaths are more than twice as high among African American men. Dr. Podgorski said that African-Americans are diagnosed with prostate cancer earlier in life and the disease is often in a more aggressive form at the time of diagnosis.
Oddly, there are no significant differences in prognosis between African-American and European-American men when the cancer is diagnosed before spreading to other organs. Yet, when diagnosed in advanced stages, the likelihood the cancer will return is much higher in African-Americans.
Dr. Podgorski noted that while it is likely genetic and environmental factors such as diet and chemical exposure contribute to prostate cancer risk and progression, researchers don’t yet know the reasons for the racial differences in the cancer’s aggressiveness. Recent clinical studies demonstrate that metabolic syndrome -- abdominal obesity, high blood pressure, high levels of triglycerides, low HDL cholesterol and high fasting glucose – plays a key role in the development of prostate cancer. Men with metabolic syndrome may have more aggressive tumors and be more likely to experience reccurrence after initial surgery.
High blood pressure and obesity are often associated with metabolic syndrome in African-Americans. Among this population, the risk of developing high blood pressure has recently been linked to low levels of a hormone called adiponectin, and high levels of proteins associated with inflammation. Research has also suggested that the distribution of specific forms of adiponectin in blood and not the levels of the total protein are associated with high blood pressure and insulin resistance, indicating biological factors related to metabolic syndrome may play a role in racial disparities in prostate cancer aggressiveness and prognosis.
Dr. Podgorski’s study will search for indicators of prostate cancer in the blood of prostate cancer patients. Those biomarkers may include proteins and genes associated with metabolic syndrome and related conditions such as inflammation, insulin resistance and oxidative stress and which may be responsible for racial differences in prostate cancer aggressiveness and prognosis.
“Overall, these studies will help us understand which factors are responsible for racial differences in prostate cancer risk, progression and responsiveness to treatment,” Dr. Podgorski said. “We expect that these studies will demonstrate that metabolic syndrome-related inflammation, insulin resistance and oxidative stress influence prostate cancer progression in African-American men differently than they do in European-American men.”
The findings, she said, should result in identification of novel biomarkers for the detection and prognosis of aggressive prostate cancer and of biological targets for improved therapy or prevention of aggressive forms of the disease. The study results will provide the basis for future validation of blood indicators as biological targets for improved therapy and prevention of aggressive cancer.
The study will collect blood samples from a large number of African-American and European-American prostate cancer patients recruited for a recently funded study on metabolic syndrome and prostate cancer. Dr. Podgorski will determine the levels of adiponectin in the samples and the levels of 15 proteins associated with inflammation, insulin resistance and oxidative stress in an effort to determine how different forms of adiponectin correlate with the biomarkers and how this relationship predicts cancer aggressiveness and racial differences. She will also, in collaboration with Cathryn Bock, Ph.D., M.P.H., and Jennifer Beebe-Dimmer, Ph.D., M.P.H., both assistant professors of the Department of Internal Medicine and the Karmanos Cancer Institute, study differences in DNA sequences of 34 genes related to inflammation, insulin resistance and oxidative stress to discover how differences predict the risk of aggressive prostate cancer and recurrence in the groups of men.
The project and grant, Dr. Podgorski said, resulted from collaboration with Isaac Powell, M.D., a professor of Urology at the Wayne State University School of Medicine and Karmanos Cancer Institute, on his study, “The Influence of Metabolic Syndrome on Prostate Cancer Progression and Risk of Recurrence in African-American and European-American Men,” which was funded last year.
