Prostate cancer is the most common visceral cancer in men and the second leading cause of cancer-related deaths in men in the United States. Racial differences in prostate cancer incidence and mortality are well documented. The incidence and mortality for prostate cancer is about twofold higher in African American versus Caucasian men, with African American men presenting more aggressive and advanced disease worldwide. This disparity in prostate cancer is believed to be a complex combination of socioeconomic factors, environment, and genetics. Thus, in order to effectively eliminate prostate cancer disparity, we need to understand the genetics involved in the disease pathway.

Prostate cancer cells carry a myriad of genetic and epigenetic abnormalities that cause prostate cancer cells to grow in an uncontrolled way by inactivating key regulatory genes known as tumor suppressors or activating tumor promoting gene expression. Several studies show that epigenetic changes including DNA methylation occurs very early in the disease pathway. We have found differential methylation changes of several key regulatory genes in prostate tissues from African American versus Caucasian men. If this is true, epigenetic changes could potentially be the link between environmental and genetic predisposition to prostate cancer. In order to explore this possibility, we propose to study genome-wide DNA methylation changes in prostate tissues from African American versus Caucasian men. These are important studies for several reasons. First, differences in epigenetic changes in African American versus Caucasian men may help in understanding how genetic factors or environmental exposures (or both) contribute to prostate cancer disparity. Second, studies proposed here could lead to the identification of novel ("ethnic sensitive") biomarkers that can predict disease aggression and improve correlations between epigenetic changes and prostate tissue pathological features such as stage, grade, and recurrence. Furthermore, because epigenetic DNA methylation changes are reversible, epigenetic drugs are being explored for reversing somatic epigenetic defects. Thus, studies could potentially lead to the identification of novel epigenetic targets for prostate cancer treatment.