High Intraprostatic Androgens in African American Men Primes for Aggressive Prostate Cancer
Abstract
There is a prostate cancer disparity in African American men, who are often diagnosed at a younger age, have more aggressive disease, and are more than twice as likely to die from the disease compared to white men. There is an urgent and dire need to reduce the human toll of this disease and improve our understanding of prostate cancer in African American men. Clinical trials have shown that having low levels of the hormone testosterone reduces the risk of prostate cancer. Animal models of prostate cancer are driven by elevated testosterone. Testosterone is an androgen sex hormone and is responsible for visible male traits and other more subtle effects. The above studies are based on systemic (circulating) levels of testosterone. We sought to determine the levels of testosterone and its active form, dihydrotestosterone, within the prostate tissue of a diverse cohort of prostate cancer patients. We found that African American men have higher levels of the active form of testosterone, dihydrotestosterone, inside their prostates. We hypothesize that this high level of dihydrotestosterone in the prostate promotes the development of more aggressive cancers and is the underpinning of the prostate cancer disparity in African American men. Herein, we have two goals. The first is to determine the downstream targets and effects of androgens in patient-derived models of prostate cancer. Second, we will examine whether adaptation to higher levels of androgen results in cancer cell behaviors consistent with aggressive disease. The study uses patient-derived models of human prostate from African American and white prostate cancer patients in the Chicago area. The findings of this proposal may lead to several clinical applications. First, we may reveal new androgen-regulated genes in African American prostates that may be useful for cancer screening or as therapeutic targets. Secondly, the prostate levels of dihydrotestosterone may serve as an early screening to identify high-risk patients. Third, this work complements another study in which we are examining vitamin D deficiency as the cause of the high prostate dihydrotestosterone in black men. Taken together, within the next 4 years, our data may support a clinically actionable approach to reducing prostate dihydrotestosterone and ultimately cancer risk in the African American population by reducing vitamin D deficiency.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Mar 10, 2021
- Source ID
- W81XWH2010182
Entities
People
- Larisa Nonn
Organizations
- United States Army
- University of Illinois at Chicago