Integrated Genomic Biomarkers to Identify Aggressive Disease in African Americans with Prostate Cancer
Abstract
Approximately 80% of men diagnosed with prostate cancer die from other causes. Therefore, primary treatment, whether it is surgery or radiation, is curative for most men. This is largely due to the fact that prostate cancer is the only cancer with a blood-based biomarker, namely prostate specific antigen (PSA), which allows for early detection. Unfortunately, a large number of men (~33,000) die each year from prostate cancer because PSA is not well suited for predicting risk of disease recurrence. After surgery, for example, some men might benefit from adjuvant treatment while others may be fine with regularly scheduled check-ups by their urologist. Thus, it is imperative that robust methods be developed for risk stratification of prostate tumors to enable men and their physicians to safely select between post-treatment surveillance and immediate adjuvant therapy. This is even more urgent for African American men who have higher prostate cancer mortality rates than age-matched white American males. This discrepancy may be due to the tumor biology. Our working hypothesis is that information about the DNA within the tumor can serve as a component of recurrence risk assessment and be applied in treatment planning to reduce this health disparity. We hypothesize that DNA-based biomarkers of disease aggressiveness and prognosis interrogated with two different, yet complementary tumor genotyping platforms can aid in the post-primary treatment decision making for African Americans with prostate cancer. Biomarkers are a broad term for molecules associated with tumor cells, in this case DNA fragments, which can be detected in sources such as tumor tissue obtained from surgical and/or biopsy sample. Tumor genotyping is a way to determine a unique signature or fingerprint of the tumor s DNA. The proposed study will involve evaluating published DNA biomarkers (some by this team) and the discovery of African American specific biomarkers of disease recurrence. Strengths of our approach include that our multidisciplinary collaborative research team will use DNA, a robust bioanalyte that will translate well into a clinical assay and evaluate the tumor s DNA signature by two different techniques. This dual platform approach will give a more complete picture of the DNA s fingerprint. A biomarker panel that integrates data from DNA-based alterations detected by two different techniques can capitalize on the synergistic and unique information provided by both views of the tumor genome to improve the prediction of prostate cancer recurrence in African American men. The successful identification and validation of biomarkers that offer substantially improved predictive and prognostic accuracy would bring extraordinary potential to improve care of African Americans with prostate cancer. With approximately 35,430 African American men estimated to be diagnosed with prostate cancer in 2013 and 4,980 estimated to die from their disease, it is important to identify appropriate prognostic genomic biomarkers in this underserved population to reduce this health disparity.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Apr 04, 2016
- Source ID
- W81XWH1510395
Entities
People
- Albert M Levin
Organizations
- Henry Ford Health
- United States Army