Prostate cancer is one of the most common cancers in men in the United States. African American men and men with a family history of prostate cancer are at increased risk for this disease. While no "prostate cancer genes" have yet been identified, several genetic changes have been shown to increase the risk for prostate cancer. However, there is no understanding of what these genetic changes mean when screening men for prostate cancer. Questions that remain include: Do these genetic changes identify men who may develop PCA earlier than later in life? Does the PSA (a blood test to screen for prostate cancer) predict prostate cancer more accurately in men with more of these genetic changes? Should high-risk men with these genetic changes be screened more frequently than yearly? Is there a prevention option for men with these genetic changes? My long-term career goal is to answer these questions by understanding how genetic changes can be used for the early detection of prostate cancer high-risk men, especially in African American men. As a medical oncologist (cancer doctor), I see how prostate cancer kills men every year. I hope to become a successful physician-scientist with expertise in laboratory science (analyzing genetic changes) and apply these findings to the screening setting (use genetic changes to help detect prostate cancer early for cure). To this end, the training program proposed in this grant will allow me to gain knowledge in cancer genetics, translational cancer prevention research, cancer risk assessment, and epidemiology. My mentors are experts in these areas, and each step of this project correlates with gaining knowledge in these areas.

The purpose of this study is to investigate if five known genetic changes affect the time to development of prostate cancer, and if this differs between African American men and Caucasian men. We will then determine if the PSA is a better or worse test for indicating prostate cancer in men who have these genetic changes compared to men without them. We will finally identify genetic changes in prostate tissues of African American men who have been diagnosed with prostate cancer to identify new genes to study in the future. These objectives will be examined in men enrolled in the Prostate Cancer Risk Assessment Program (PRAP) at Fox Chase Cancer Center (FCCC), a prostate cancer early detection and research program for men at high risk. Men with a family member with prostate cancer and African American men are eligible for PRAP and undergo screening for prostate cancer. Currently, 700 men participate in PRAP (60% African American), with men having enrolled since 1996. A large percent of these men have been diagnosed with aggressive disease at a young age due to our efforts. Due to the 12-year time span of screening information in PRAP, we can use the screening information to almost immediately determine the practical applications of genetic changes in prostate cancer screening. Understanding the use of genetic changes in these men will be crucial to detect prostate cancer at a curable point and prevent unnecessary prostate biopsies. Therefore, this study can be applied to screening high-risk men within 2 years with the practical applications being: (1) screen men with early-onset prostate cancer every 6 months vs. once a year, (2) recommend prostate biopsies at lower PSA values if we find the PSA predicts prostate cancer in men who have more of these genetic changes, or (3) detect prostate cancer early in African American men. We will be able to improve cure from prostate cancer, especially in African American men.