Comprehensive Genetic Characterization of Intraprostatic Chronic Inflammation and Prostate Cancer in African American Men
Abstract
Prostate cancer affects 1 in 6 men during their lifetime. One of the biggest risk factors for prostate cancer is race. Importantly, African American men are at the highest risk for developing prostate cancer. Studies have shown that chronic inflammation of the prostate may increase the risk of developing prostate cancer. Long-term prostate inflammation is linked to more aggressive forms of prostate cancer. In many types of cancer, inflammation causes damage to DNA, which leads to the development of cancer. Since African American men are at higher risk for both inflammation and prostate cancer, understanding the genetic changes leading to prostate cancer is crucial. In this research project, we propose characterizing DNA alterations influencing prostate cancer development in African American men using cutting-edge whole genome sequencing. We will use 20 radical prostatectomy tissue samples from African American patients with both chronic inflammation and prostate cancer. For tissue samples, tumor and noncancerous tissue will be retrieved with laser capture microdissection. DNA isolated from whole blood from each patient will be used as a normal tissue control. We intend to identify genes important to prostate tumor evolution by comparing prostate cancer tumor tissue to non-cancerous prostate tissue with inflammation. Identifying the very early genetic changes in inflammation and prostate cancer in African American men may provide a new understanding of prostate cancer racial disparity. It may also offer opportunities to improve treatment of chronic inflammation as well as prostate cancer. This proposal concentrates on African American prostate cancer patients. As a disproportionately affected population that has been underrepresented in prostate cancer genetic studies, the present proposal may give innovative genetic insights into both prostate inflammation and prostate cancer. Since prior research has linked inflammation and prostate cancer risk, identification of early genetic events shared between chronic inflammation and prostate cancer may pave the way for the development of biomarkers specific for prostate cancer risk assessment, early detection, and diagnosis of prostate cancer. Since chronic inflammation has been linked with aggressive prostate cancer, the DNA changes identified may potentially provide an early diagnostic profile for distinguishing aggressive from non-aggressive prostate cancer in newly diagnosed African American men. Once important genes have been verified in a larger population, a genetic profile may be developed and used in a clinical setting. This type of genetic knowledge may empower patients and doctors to make personalized treatment decisions and ultimately improve treatment outcomes. However, this type of genetic information alone would not be sufficient to predict and prevent a complex disease such as prostate cancer. For some patients, genetic testing may cause anxiety or guilt. Therefore, it will be crucial that any genetic findings be thoroughly validated and explained to the patients in their proper context. Given the significance of any genetic findings, all genetic biomarkers must be carefully explored through carefully controlled clinical trials, which may take years of development. My primary career goal is to become an independent translational researcher in the field of prostate cancer genetics and biomarker development. Specifically, based on my early work in hereditary prostate cancer in African Americans to my present work in inflammation, my present and long-term goal is to help describe the genetic mechanisms driving prostate cancer. This will be accomplished by investigating the racial prostate cancer disparity and genetic complexity in all aspects of prostate cancer development. Successful completion of the proposed research plan will be dependent on utilizing the rich multidisciplinary environment available at Tulane University School of Medicine
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Apr 04, 2016
- Source ID
- W81XWH1510379
Entities
People
- Elisa M Ledet
Organizations
- Tulane University of Louisiana
- United States Army