Bladder cancer is a significant health problem in the United States and throughout the world. An estimated 56,500 cases will be diagnosed this year in the U.S. alone. One of the highest risk groups for developing bladder cancer is former smokers. Smokers have more than a four-fold increased risk for developing bladder cancer as compared with non-smokers. The high risk of former smokers for developing bladder cancer and the extended period of time which typically elapses prior to the observation of bladder cancer in these individuals make them appropriate for following with markers that can detect the disease early as well as the application of chemopreventive agents in those identified with early disease. Instead of treating all smokers with chemopreventive agents as a first course, we are proposing to apply a biomarker which appears to specifically and sensitively detect bladder cancer at an early stage in its development and then focus the chemopreventive agents on these individuals. If these studies prove successful, these chemopreventive approaches can then be applied to the large population of former smokers using the marker, BLCA-4, as a measure of effectiveness. When bladder cancer is detected early, the five-year survival rate is approximately 94% while patients with disease that has spread, have significantly lower survival rates. The hypothesis being addressed here is that urine levels of BLCA-4 can serve as a surrogate biomarker to evaluate chemopreventive agents in an animal model of bladder cancer. To address this hypothesis we propose the following specific aims: 1. To examine the time course of BLCA-4 expression in the development of bladder cancer utilizing an animal model of the disease representing former smokers. 2. To determine the utility of BLCA-4 as a surrogate marker of bladder cancer permitting the rapid evaluation of chemopreventive compounds. 3. To test in a pilot study, the use of BLCA-4 as a biomarker with which to detect bladder cancer in former smokers at an early stage, prior to the development of gross lesions and therefore making them candidates for chemopreventive therapies both intravesically as well as systemic.
