Racial Disparities in Metformin Use as Potential Prostate Cancer Therapy

PUBLIC ABSTRACT

Training in a socialized medicine system (India) gave me unique insight into how the system, although designed to deliver care to all, under serves minorities and the economically disadvantaged. On completing my residency training in surgery, I sought to obtain research skills that would give me a global perspective on the excess disease burden among minorities. I was fortunate to join a group that offered me an all-inclusive outlook on how clinical research is done. I was immediately attracted to prostate cancer (PCa) because of its prevalence and the clinical challenges it represents. Also, I realized even in the United States, where technical expertise in medicine is among the best, disease prevalence and health care delivery are inequitably distributed among minorities. Under the guidance of Dr. Stephen Freedland, I was actively involved in outcomes research using data from men within the Shared Equal Access Regional Cancer Hospital (SEARCH) database. Even in an equal access setting, such as the Veterans Affairs hospitals, I saw African American men (AAM) had more aggressive disease and increased cancer recurrence, and I saw how obesity played a major role in influencing poor disease features. This prompted me to study how obesity affected AAM and Caucasian men (CM), and I had the opportunity to present my findings in various international forums. Also, I partook in all the academic programs of the Division of Urology at Duke University. In short, working with this group has provided me with both an initial impetus and a broad base, which will help my transition as a health disparities researcher.

Many milestones in modern medicine were achieved by answering research questions that initially arose from the bedside. Thus, after completing this fellowship, I will pursue a urology residency followed by a clinical fellowship in urologic oncology. The training I receive in the course of these two years will provide me the requisite tools to optimize my time for focused research on health disparities during the residency and fellowship period. Ultimately, I aim to practice medicine as an academic urologist with a particular focus on PCa research and health disparities. This will allow me the opportunity to impart the knowledge I gain to future generations of physicians and researchers, and shape their minds to the cause of minimizing the excess burden of disease among minorities.

My 2-year training program includes a research and interactive learning component involving coursework, seminars, journal clubs, and conferences. The program will be under the supervision of Dr. Stephen Freedland, a well-known authority in the field of PCa racial disparity. Given his successes, he is an outstanding role model and someone I would like to emulate. The didactic portion will involve formal training through completion of a Masters of Public Health (MPH) in Epidemiology at the University of North Carolina at Chapel Hill (UNC-CH), which is one of the top public health courses in the US. This program will provide a solid foundation of population health knowledge and research skills on which to build. The coursework will emphasize racial inequalities in the US.

In this project, I will study the link between metformin (a common drug for blood sugar control in diabetes) and improved outcomes after PCa surgery. Some studies suggest metformin may reduce both getting cancer and dying from it. Also, studies suggest AAM are less compliant with metformin use, depriving them of the potential anti-cancer benefits of metformin and increasing their chances of diabetes complications. The proposed study will be done using the SEARCH database, which has information on over 1700 men, of which 40% are AAM. Of note, prior studies examining the association between metformin and cancer had minimal representation of AAM, and the associations with PCa are unexplored. We will study the association between metformin and aggressive PCa and cancer recurrence, and whether benefits are lower in AAM due to poor compliance with metformin use.

We expect to find metformin linked with lower risk of having aggressive PCa and cancer recurrence, but AAM will be less compliant with metformin, thus deriving less benefit. If we show this, it will present a strong case to ensuring diabetic men, especially AAM, use metformin regularly. This approach would increase optimal diabetes management and reduce complications due to diabetes. Though early studies suggested metformin was linked with rare metabolic abnormalities, recent studies have shown the risk is very low. Thus, if we show metformin reduces cancer progression, the benefits would far outweigh any risks. In summary, this project has the potential to improve racial disparities in two major public health problems -- PCa and diabetes.