A majority of aging men develop benign and/or malignant prostatic growth. One out of six American men is diagnosed with prostate cancer in his lifetime, and 1/2 develops benign prostatic hyperplasia (BPH). The Prostate Cancer Prevention Trial recently demonstrated a 25% incidence of prostate cancer in U.S. men > 55 years of age over a 7 year period. Currently used screening tests (serum prostate-specific antigen (PSA) and digital rectal exam) have shown only modest predictive value, and serum PSA isoforms have added little specificity. Body fluids such as urine may contain molecular information regarding the presence of prostate cancer. I propose to study several recently-identified molecular changes commonly associated with prostate neoplasia as biomarkers for prostate cancer in urine, in the hopes of improving the specificity of noninvasive detection efforts. Three urinary analyses will form the cornerstones of this study: methylation of DNA at CpG islands of the pi-class glutathione-s transferase (GSTP1) promoter, a noncoding RNA """"""""differential display 3"""""""" (DD3), and the protein alpha methylacyl CoA racemase (AMACR). My main aim is to learn how to evaluate and study new cancer biomarkers. As a urologic surgeon with a background in molecular biology, this will require formal training in biostatistics, study design, biomarker applications, and data analysis. My institution and department are supporting my efforts to formally study biomarkers and also develop a clinical expertise in prostate disease. My department has created many leaders in prostate disease research due to its productive, translational, and open research environment. The sponsorship of two world leaders in prostate cancer and BPH, and regular didactic interactions with them and a prostate cancer biostatistician, will allow my career training goal to be met. Over a 5-year period of study, I will have learned how to critically evaluate biomarkers, collect biomarker data, and interpret it properly. Hopefully, useful biomarker information for prostate cancer will also result from my period of study.
