The Contribution of SELENOF to the Disproportionate Mortality Experienced by African American Men Due to Prostate Cancer
Abstract
The management of prostate cancer (PCa) remains a significant challenge, with an estimated 180,890 men being diagnosed with the disease and 26,120 men dying from PCa in 2016, according to the American Cancer Society, making death from PCa the second leading cause of death among American men. The problem of prostate cancer is disproportionate for African American men, who have both the highest incidence and mortality from PCa compared to the other races assessed. The reasons for this are likely multi-factorial, including reduced access to care, as well as other socio-economic factors. The identification of such risk factors that predominate among African American men will be critical in reducing the risk of dying of PCa in that population, as well as identifying risk factors in the population at large. The SELENOF protein has been implicated in PCa risk and mortality by human genetics. We have established that SELENOF is greatly reduced in PCa compared to normal-appearing prostatic tissue, and its levels are lower in PCa from African American men compared to PCa from Caucasians. This is likely due to our observation that the DNA of African Americans contains a genetic difference, approximately 10-fold more frequent in African Americans, that is likely to determine those lower levels. Based on published work and the preliminary data included in the application, we hypothesize that reduced levels of SELENOF contribute to the risk of experiencing and dying from PCa, and the differences in the SELENOF gene between African American and Caucasian men contributes to the increased risk in that population. The work proposed in our application is designed to establish a PCa risk factor that is more predominant among African Americans compared to Caucasians. This is critical in establishing new means to identify men who are at increased risk so that they can obtain better surveillance, as the identification of PCa at early stages greatly enhances the chances of cure and survival. This can be accomplished by either genetic testing using DNA from any physical location, such as cheek cells for example, or by the assessment of SELENOF levels directly from prostate biopsies obtained from men with suspicious clinical findings that merited the biopsy. Knowing the risk of aggressive disease is a valuable tool to the managing clinician in monitoring the patient and determining the best treatment options when warranted. The results of the proposed research could immediately be expanded into larger studies to establish the clinical value of such testing. A long-term benefit from the proposed research comes from the identification of a potential target for new drug development. As part of the proposed studies, we intend to determine not only the biological consequences of the reduction in SELENOF in PCa and African Americans, but also whether the restoration of SELENOF suppresses the growth of cancer cells. Were this to happen, novel approaches to restore SELENOF levels can be aggressively pursued as a new approach to managing existing PCa. It should be stated that, although the genetic trait we are investigating is significantly more frequent among African Americans, its presence in the population at large indicates that there may be benefits to many men who are not African American. As stated above, mitigating the disparity in PCa risk and outcome among African Americans requires the identification of candidate factors for study and targeting. Research as a consequence of our identification of a dramatic genetic difference and lower levels of the corresponding protein in tissues in African Americans compared to Caucasians is anticipated to make a major contribution to understanding why this population is at greater risk, lead to interventions to mitigate that risk, and generally enhance the understanding of the growth control that exists in the prostate.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Oct 29, 2018
- Source ID
- W81XWH1810338
Entities
People
- Alan M Diamond
Organizations
- United States Army
- University of Illinois at Chicago