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Effect of α1-Adrenoceptor Antagonist Exposure on Prostate Cancer Incidence: An Observational Cohort Study

2007; Lippincott Williams & Wilkins; Volume: 178; Issue: 5 Linguagem: Inglês

10.1016/j.juro.2007.06.043

1527-3792

Andrew Harris, Brad W. Warner, John M. Wilson, Aaron Becker, Randall G. Rowland, William T. Conner, Matthew Lane, Kimberly D. Kimbler, Eric B. Durbin, Andre T. Baron, Natasha Kyprianou,

Urinary Bladder and Prostate Research

No AccessJournal of UrologyInvestigative urology1 Nov 2007Effect of α1-Adrenoceptor Antagonist Exposure on Prostate Cancer Incidence: An Observational Cohort Studyis companion ofProstate Cancer Risk Assessment Program: A 10-Year Update of Cancer DetectionNovel Targeted Pro-Apoptotic Agents for the Treatment of Prostate Cancer Andrew M. Harris, Bradley W. Warner, John M. Wilson, Aaron Becker, Randall G. Rowland, William Conner, Matthew Lane, Kimberly Kimbler, Eric B. Durbin, Andre T. Baron, and Natasha Kyprianou Andrew M. HarrisAndrew M. Harris Division of Urology, Department of Surgery, College of Medicine, University of Kentucky, Lexington, Kentucky More articles by this author , Bradley W. WarnerBradley W. Warner Division of Urology, Department of Surgery, College of Medicine, University of Kentucky, Lexington, Kentucky More articles by this author , John M. WilsonJohn M. Wilson Division of Urology, Medical University of Ohio, Toledo, Ohio More articles by this author , Aaron BeckerAaron Becker Division of Urology, Medical University of Ohio, Toledo, Ohio More articles by this author , Randall G. RowlandRandall G. Rowland Division of Urology, Department of Surgery, College of Medicine, University of Kentucky, Lexington, Kentucky More articles by this author , William ConnerWilliam Conner Division of Urology, Department of Surgery, College of Medicine, University of Kentucky, Lexington, Kentucky Lexington Veterans Affairs Medical Center, Markey Cancer Center, Lexington, Kentucky More articles by this author , Matthew LaneMatthew Lane Lexington Veterans Affairs Medical Center, Markey Cancer Center, Lexington, Kentucky More articles by this author , Kimberly KimblerKimberly Kimbler Department of Epidemiology, College of Public Health, University of Kentucky, Lexington, Kentucky Division of Hematology Oncology, Blood and Marrow Transplantation, Markey Cancer Center, Lexington, Kentucky More articles by this author , Eric B. DurbinEric B. Durbin Kentucky Cancer Registry, Cancer Bioinformatics Division, Markey Cancer Center, Lexington, Kentucky More articles by this author , Andre T. BaronAndre T. Baron Department of Epidemiology, College of Public Health, University of Kentucky, Lexington, Kentucky Division of Hematology Oncology, Blood and Marrow Transplantation, Markey Cancer Center, Lexington, Kentucky More articles by this author , and Natasha KyprianouNatasha Kyprianou Division of Urology, Department of Surgery, College of Medicine, University of Kentucky, Lexington, Kentucky Department of Molecular and Cellular Biochemistry, College of Medicine, University of Kentucky, Lexington, Kentucky More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2007.06.043AboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract Purpose: The quinazoline based α1-adrenoceptor antagonists doxazosin and terazosin suppress prostate tumor growth via the induction of apoptosis and decrease in tissue vascularity. To assess the effect of α1-blocker exposure on the incidence of prostate cancer we performed an exploratory, observational cohort study. Materials and Methods: The medical records of all male patients enrolled at Lexington Veterans Affairs Medical Center were searched to identify men treated with quinazoline based α1-adrenoreceptor antagonists between January 1, 1998 and December 31, 2002 for hypertension and/or benign prostatic enlargement. Medical records were subsequently linked to the Markey Cancer Center Kentucky Cancer Registry, a statewide population based central cancer registry that is part of the National Cancer Institute Surveillance, Epidemiology and End Results Program, to identify all incident prostate cancer cases diagnosed. All newly diagnosed prostate cancer cases unexposed to α1-adrenoreceptor antagonists in the total male Veterans Affairs population during this period were also identified from the Kentucky Cancer Registry database. Measures of disease incidence, relative risk and attributable risk were calculated to compare the risk of prostate cancer in α1-blocker exposed vs unexposed men. Kaplan-Meier curves and Cox regression models were used to compare overall survival between α1-blocker exposed and unexposed prostate cancer cases. Results: Our analysis revealed a cumulative incidence of 1.65% in α1-blocker exposed men compared to 2.41% in the unexposed group. These data yielded an unadjusted RR of 0.683 (95% CI 0.532, 0.876) and a risk difference of −0.0076, indicating that 7.6 fewer prostate cancer cases developed per 1,000 exposed men. Thus, exposure to quinazoline α1-blockers may have prevented 32 prostate cancer cases among the 4,070 treated men during the study period. Therefore, men exposed to quinazoline α1-adrenoceptor antagonists were at 1.46 times lower RR and 31.7% lower attributable risk for prostate cancer than unexposed men. There was no association between α1-adrenoceptor antagonist exposure and overall survival. Conclusions: These data suggest that exposure to quinazoline based α1-adrenoceptor antagonists significantly decreases the incidence of prostate cancer. This evidence suggests that the apoptotic and anti-angiogenic effects of these drugs may prevent the development of prostate cancer. References 1 : Cancer statistics, 2006. CA Cancer J Clin2006; 56: 106. Google Scholar 2 : Treatment options for prostate cancer: evaluating the evidence. Am Fam Physician2005; 71: 1915. Google Scholar 3 : Novel targeting of apoptosis pathways for prostate cancer therapy. Curr Cancer Drug Targets2004; 4: 85. Google Scholar 4 : An interdisciplinary approach to treating prostate cancer. Urology2005; 65: 13. Google Scholar 5 : The long-term effect of doxazosin, finasteride, and combination therapy on the clinical progression of benign prostatic hyperplasia. N Engl J Med2003; 349: 2387. 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Google Scholar © 2007 by American Urological AssociationFiguresReferencesRelatedDetailsCited byWalsh P (2018) Urological Oncology: Prostate CancerJournal of Urology, VOL. 183, NO. 1, (158-163), Online publication date: 1-Jan-2010.Related articlesJournal of Urology14 Sep 2007Prostate Cancer Risk Assessment Program: A 10-Year Update of Cancer DetectionJournal of Urology14 Sep 2007Novel Targeted Pro-Apoptotic Agents for the Treatment of Prostate Cancer Volume 178Issue 5November 2007Page: 2176-2180 Advertisement Copyright & Permissions© 2007 by American Urological AssociationKeywordsepidemiologyquinazolinesadrenergic alpha-antagonistsprostateprostatic neoplasmsMetricsAuthor Information Andrew M. Harris Division of Urology, Department of Surgery, College of Medicine, University of Kentucky, Lexington, Kentucky More articles by this author Bradley W. Warner Division of Urology, Department of Surgery, College of Medicine, University of Kentucky, Lexington, Kentucky More articles by this author John M. Wilson Division of Urology, Medical University of Ohio, Toledo, Ohio More articles by this author Aaron Becker Division of Urology, Medical University of Ohio, Toledo, Ohio More articles by this author Randall G. Rowland Division of Urology, Department of Surgery, College of Medicine, University of Kentucky, Lexington, Kentucky More articles by this author William Conner Division of Urology, Department of Surgery, College of Medicine, University of Kentucky, Lexington, Kentucky Lexington Veterans Affairs Medical Center, Markey Cancer Center, Lexington, Kentucky More articles by this author Matthew Lane Lexington Veterans Affairs Medical Center, Markey Cancer Center, Lexington, Kentucky More articles by this author Kimberly Kimbler Department of Epidemiology, College of Public Health, University of Kentucky, Lexington, Kentucky Division of Hematology Oncology, Blood and Marrow Transplantation, Markey Cancer Center, Lexington, Kentucky More articles by this author Eric B. Durbin Kentucky Cancer Registry, Cancer Bioinformatics Division, Markey Cancer Center, Lexington, Kentucky More articles by this author Andre T. Baron Department of Epidemiology, College of Public Health, University of Kentucky, Lexington, Kentucky Division of Hematology Oncology, Blood and Marrow Transplantation, Markey Cancer Center, Lexington, Kentucky More articles by this author Natasha Kyprianou Division of Urology, Department of Surgery, College of Medicine, University of Kentucky, Lexington, Kentucky Department of Molecular and Cellular Biochemistry, College of Medicine, University of Kentucky, Lexington, Kentucky More articles by this author Expand All Advertisement PDF downloadLoading ...