Effect of alpha1-adrenoceptor antagonist exposure on prostate cancer incidence: an observational cohort study.
OBJECTIVE
The quinazoline based alpha1-adrenoceptor antagonists doxazosin and terazosin suppress prostate tumor growth via the induction of apoptosis and decrease in tissue vascularity. To assess the effect of alpha1-blocker exposure on the incidence of prostate cancer we performed an exploratory, observational cohort study.


METHODS
The medical records of all male patients enrolled at Lexington Veterans Affairs Medical Center were searched to identify men treated with quinazoline based alpha1-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 alpha1-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 alpha1-blocker exposed vs unexposed men. Kaplan-Meier curves and Cox regression models were used to compare overall survival between alpha1-blocker exposed and unexposed prostate cancer cases.


RESULTS
Our analysis revealed a cumulative incidence of 1.65% in alpha1-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 alpha1-blockers may have prevented 32 prostate cancer cases among the 4,070 treated men during the study period. Therefore, men exposed to quinazoline alpha1-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 alpha1-adrenoceptor antagonist exposure and overall survival.


CONCLUSIONS
These data suggest that exposure to quinazoline based alpha1-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.
Harris
Andrew M
AM
Division of Urology, Department of Surgery, College of Medicine, University of Kentucky, Lexington, Kentucky 40536, USA.
Warner
Bradley W
BW
Wilson
John M
JM
Becker
Aaron
A
Rowland
Randall G
RG
Conner
William
W
Lane
Matthew
M
Kimbler
Kimberly
K
Durbin
Eric B
EB
Baron
Andre T
AT
Kyprianou
Natasha
N
D058668:Adrenergic alpha-1 Receptor Antagonists; D000317:Adrenergic alpha-Antagonists / Q000627:therapeutic use*; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents; D017292:Doxazosin / Q000627:therapeutic use; D005500:Follow-Up Studies; D006801:Humans; D015994:Incidence; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011224:Prazosin / Q000031:analogs & derivatives / Q000627:therapeutic use; D016016:Proportional Hazards Models; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000453:epidemiology* / Q000473:pathology; D012189:Retrospective Studies; D015996:Survival Rate; D016896:Treatment Outcome; D014481:United States / Q000453:epidemiology
D058668:Adrenergic alpha-1 Receptor Antagonists; D000317:Adrenergic alpha-Antagonists; D000970:Antineoplastic Agents; C041226:Terazosin; D017292:Doxazosin; D011224:Prazosin