Integrative Molecular Profiling of Whole Urine in African American Men with Aggressive Prostate Cancer
Abstract
African American men have a high incidence of prostate cancer and experience higher mortality rates relative to other racial and ethnic populations. These health disparities are rooted in several potential causes, including biologic contributors, environmental factors, social and cultural factors, and access to health care. While no single cause fully explains all of the observed disparity in prostate cancer health outcomes for African American men, there is an emerging consensus that biologic factors may have a significant impact on disease aggressiveness (FY20 PCRP Health Disparity Research Award Focus Area). Indeed, over the past two decades, a number of specific genetic changes that occur either in a patient’s own DNA (i.e., germline variants) or within tumor cells themselves (i.e., somatic alterations) show significant differences across racial and ethnic subgroups, including African American men. Most men with prostate cancer have indolent disease that can be cured with local treatment (i.e., surgery, radiation therapy, etc.). However, subsets of patients present with metastatic disease or recur and progress after local treatment, and for the vast majority of these men, systemic treatment options are not curative and may be associated with significant morbidity. Thus, early detection of aggressive disease is critical to reducing death and morbidity related to prostate cancer and should be a major focus for multi-disciplinary efforts to reduce racial and ethnic health disparities. Quantitation of serum prostate-specific antigen (PSA) is the focus of most modern prostate cancer early detection programs; however, serum PSA is an imperfect biomarker (i.e., indicator) for prostate cancer in general and aggressive disease in particular. Thus, the development, validation, and application of novel prostate cancer biomarkers to augment or replace serum PSA in early detection programs has been a major area of research interest. Indeed, over the past two decades, our group has pioneered a number of urine-based molecular tests to detect aggressive prostate cancer, including MyProstateScore (MPS) – a commercially available test performed by a government-certified laboratory at our institution. Recently, our group has developed and validated a new and innovative next-generation sequencing (NGS) approach that is able to detect prostate cancer-associated germline variants, somatic alterations, and RNA biomarkers in urine, and we have demonstrated that this NGS method is significantly better at identifying men with aggressive prostate cancer than serum PSA or other urine-based molecular tests. Based on these preliminary data, we believe that this NGS approach has the potential to significantly improve early detection of aggressive prostate cancer in African American men and thereby reduce racial disparities and lethal prostate cancer in this high-risk population (FY20 PCRP Overarching Challenges). However, the percentage of African American men in our initial study group was lower than the national average, and it remains unclear whether racial and ethnic genetic differences impact the ability of our NGS test to identify African American men with aggressive prostate cancer. Thus, the goal of this proposed research is to determine whether a novel integrative NGS approach to urine-based prostate cancer testing can augment early detection of African American men with aggressive disease. This proposed research has the potential to help high-risk populations – including African American men – with prostate cancer because it will improve the identification of men with aggressive disease so that they can be treated before their tumors spread to other parts of the body and become incurable. Furthermore, decreasing the number of African American men with metastatic prostate cancer will necessarily reduce health disparities and lethal prostate cancer in this population. Importantly, our novel and innovative NGS approach
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Dec 05, 2021
- Source ID
- W81XWH2110238
Entities
People
- Aaron Udager
Organizations
- United States Army
- University of Michigan