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PURPOPSE-Quinazoline-based α1-adrenoceptor antagonists (α1-blockers), doxazosin and terazosin, suppress prostate tumor growth via induction of apoptosis and reduction of tissue vascularity. We hypothesize that by inducing apoptosis and targeting angiogenesis these drugs serve as chemopreventive agents of human prostate cancer. We therefore performed an exploratory observational cohort study to assess whether α1-blocker exposure affects the incidence prostate cancer and overall survival experience. MATERIALS AND METHODS-The medical records of all male patients enrolled at the Lexington Veterans Administration (VA) Medical Center were searched to identify men treated with quinazoline-based α1-adrenoreceptor antagonists between Jan 1, 1998 and Dec 31, 2002 for either hypertension and/or benign prostate enlargement. Medical records were subsequently linked to the Markey Cancer Center's Kentucky Cancer Registry (KCR), a statewide population-based central cancer registry that is part of the NCI's Surveillance, Epidemiology, and End Results (SEER) Program to identify all incident prostate cancer cases diagnosed. All newly diagnosed, prostate cancer cases unexposed to α1-adrenoreceptor antagonists in the total male VA population during this time period also were identified from the KCR's database. Measures of disease incidence, relative risk, and attributable risk were calculated to compare the risk of developing prostate cancer for α1-blockerexposed versus unexposed men. Kaplan Meier curves and Cox regression models were used to compare the overall survival between α1-blocker-exposed and unexposed prostate cancer cases.RESULTS-Our analysis revealed a cumulative incidence of 1.65% among the α1-blocker-exposed men compared to 2.41% in the unexposed group. These data yield an unadjusted risk ratio of 0. NIH Public AccessAuthor Manuscript J Urol. Author manuscript; available in PMC 2007 November 21. NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript (95% CI: 0.532, 0.876) and risk difference of −0.0076, which indicates that 7.6 fewer prostate cancer cases developed per 1000 exposed men. Exposure to quinazoline α1-blockers thus may have prevented 32 prostate cancer cases among the 4070 treated men during the study period. Men exposed to quinazoline-based α1-adrenoceptor antagonists therefore, have a 1.46 times lower relative risk and 31.7% lower attributable risk of developing prostate cancer than unexposed men. There was no association between α1-adrenoceptor antagonist -exposure and overall patient survival.CONCLUSIONS-These data suggest that exposure to quinazoline-based α1-adrenoceptor antagonists significantly decreases the incidence of prostate cancer. This is the first epidemiological evidence to suggest that the apoptotic and anti-angiogenic effects of these drugs may prevent the development of prostate cancer.