Decreased risk of bladder cancer in men treated with quinazoline-based α1-adrenoceptor antagonists
- PMID: 20717483
- PMCID: PMC2921713
Decreased risk of bladder cancer in men treated with quinazoline-based α1-adrenoceptor antagonists
Abstract
Previous studies documented that human bladder cancer cells are sensitive to the apoptotic effects of quinazoline-derived α1-adrenoreceptor antagonists and bladder tumors exhibit reduced tissue vascularity in response to terazosin. More recent evidence suggests that exposure to quinazoline α1-adrenorecptor antagonists leads to a significant reduction in prostate cancer incidence. This retrospective observational cohort study was conducted to determine whether male patients treated with quinazoline α1-adrenoceptor antagonists for either benign prostate hyperplasia (BPH) or hypertension have a decreased risk of developing bladder cancer. Review of the medical records of all male patients enrolled at the Lexington Veterans Administration (VA) Medical Center identified men exposed to quinazoline-based α1-adrenoceptor antagonists (Jan 1, 1998-Dec 31, 2002) for either hypertension and/or benign prostate obstructive symptoms. The whole group of 27,138 male patients was linked to the Markey Cancer Center's Kentucky Cancer Registry (KCR), part of the NCI's Surveillance, Epidemiology, and End Results (SEER) Program, to identify all incident bladder cancer cases diagnosed in this population. Measures of disease incidence, relative risk, and attributable risk were calculated to compare the risk of developing bladder cancer for α1-blocker-exposed versus unexposed men. A two-by-two contingency table of α1-antagonist exposure versus bladder cancer diagnoses was constructed and the relative risk was calculated. Our analysis revealed a cumulative bladder cancer incidence of 0.24% among the α1-blocker-exposed men compared to 0.42% in the unexposed group. Thus, there was a risk difference of -0.0018, which indicates that 1.8 fewer bladder cancer cases developed per 1000 exposed men. Alternatively stated, 556 men would need to be treated with quinazoline α1-blockers to prevent one case of bladder cancer. Exposure to quinazoline α1-blockers thus may have prevented 7 to 8 bladder cancer cases among the 4173 treated men during the study period. The data yield an unadjusted risk ratio of 0.57 (95% CI: 0.30, 1.08) and therefore, men treated with α1-adrenoreceptor antagonists have a 43% lower relative risk of developing bladder cancer than unexposed men (p=0.083). Our inability to determine person-years at risk of developing bladder cancer for each unexposed control patient, was a limitation for calculating an incidence ratio and rate difference. These results offer an initial indication that exposure to doxazosin and terazosin decreases the incidence of bladder cancer. This is the first epidemiological evidence that the anti-tumor action of quinazoline-based α1-antagonists may potentially translate into a protective effect from bladder cancer development.
Similar articles
-
Effect of alpha1-adrenoceptor antagonist exposure on prostate cancer incidence: an observational cohort study.J Urol. 2007 Nov;178(5):2176-80. doi: 10.1016/j.juro.2007.06.043. Epub 2007 Sep 17. J Urol. 2007. PMID: 17870114 Free PMC article.
-
Quinazoline-derived alpha1-adrenoceptor antagonists induce prostate cancer cell apoptosis via an alpha1-adrenoceptor-independent action.Cancer Res. 2002 Jan 15;62(2):597-602. Cancer Res. 2002. PMID: 11809715
-
Reduction of human prostate tumor vascularity by the alpha1-adrenoceptor antagonist terazosin.Prostate. 2001 Jul 1;48(2):71-8. doi: 10.1002/pros.1083. Prostate. 2001. PMID: 11433417
-
Apoptotic impact of alpha1-blockers on prostate cancer growth: a myth or an inviting reality?Prostate. 2004 Apr 1;59(1):91-100. doi: 10.1002/pros.10357. Prostate. 2004. PMID: 14991869 Review.
-
Doxazosin and terazosin suppress prostate growth by inducing apoptosis: clinical significance.J Urol. 2003 Apr;169(4):1520-5. doi: 10.1097/01.ju.0000033280.29453.72. J Urol. 2003. PMID: 12629407 Review.
Cited by
-
Prostate cancer incidence and mortality in men exposed to α1-adrenergic receptor antagonists.J Natl Cancer Inst. 2024 Sep 1;116(9):1459-1465. doi: 10.1093/jnci/djae108. J Natl Cancer Inst. 2024. PMID: 38718219 Free PMC article.
-
Doxazosin, a Classic Alpha 1-Adrenoceptor Antagonist, Overcomes Osimertinib Resistance in Cancer Cells via the Upregulation of Autophagy as Drug Repurposing.Biomedicines. 2020 Aug 5;8(8):273. doi: 10.3390/biomedicines8080273. Biomedicines. 2020. PMID: 32764319 Free PMC article.
-
Partial agonist activity of α1-adrenergic receptor antagonists for chemokine (C-X-C motif) receptor 4 and atypical chemokine receptor 3.PLoS One. 2018 Sep 24;13(9):e0204041. doi: 10.1371/journal.pone.0204041. eCollection 2018. PLoS One. 2018. PMID: 30248140 Free PMC article.
-
Role of α- and β-adrenergic signaling in phenotypic targeting: significance in benign and malignant urologic disease.Cell Commun Signal. 2021 Jul 20;19(1):78. doi: 10.1186/s12964-021-00755-6. Cell Commun Signal. 2021. PMID: 34284799 Free PMC article. Review.
-
Repurposing of α1-Adrenoceptor Antagonists: Impact in Renal Cancer.Cancers (Basel). 2020 Aug 28;12(9):2442. doi: 10.3390/cancers12092442. Cancers (Basel). 2020. PMID: 32872127 Free PMC article.
References
-
- Benning CM, Kyprianou N. Quinazoline-derived alpha1-adrenoceptor antagonists induce prostate cancer cell apoptosis via an alpha1-adrenoceptor-independent action. Cancer Res. 2002;62:597–602. - PubMed
-
- Bochner BH, Cote RJ, Weidner N, Groshen S, Chen SC, Skinner DG, Nichols PW. Angiogenesis in bladder cancer: relationship between microvessel density and tumor prognosis. J Natl Cancer Inst. 1995;87:1603–1612. - PubMed
-
- Caine M. α-adrenergic blockers for the treatment of benign prostatic hyperplasia. Urol Clin North Am. 1990;17:641–649. - PubMed
-
- Chapple CR, Carter P, Christmas TJ, Kirby RS, Bryan J, Milroy EJ, Abrams P. A three month double-blind study of doxazosin as treatment for benign prostatic bladder outlet obstruction. Br J Urol. 1994;74:50–56. - PubMed
-
- Chiang CF, Son EL, Wu GJ. Oral treatment of the TRAMP mice with doxazosin suppresses prostate tumor growth and metastasis. Prostate. 2005;64:408–418. - PubMed
Grants and funding
LinkOut - more resources
Full Text Sources
Research Materials