title: Association of clinical benign prostate hyperplasia with prostate cancer incidence and mortality revisited: a nationwide cohort study of 3,009,258 men.
abstract: BACKGROUND
  Although benign prostate hyperplasia (BPH) and prostate cancer (PCa) share features such as hormone-dependent growth and response to treatment with antiandrogen therapy, BPH is generally not considered a premalignant lesion.
  
  
  OBJECTIVE
  To determine whether clinical BPH is associated with an increased risk of PCa incidence and mortality.
  
  
  METHODS
  Using designs with individual participant data from five national registries, we studied the entire Danish male population from 1980 through 2006, a total of 3,009,258 Danish men. We collected PCa diagnoses (n=53,315), information on PCa mortality (n=25,459), and ascertained clinical BPH (not histologically proven BPH) through hospitalization (n=187,591) and/or surgery (n=77,698) from 1980 to 2006 and the use of α-adrenergic receptor antagonists (n=143,365) and/or the use of 5α-reductase inhibitors (5-ARIs) (n=47,465) from 1995 to 2006.
  
  
  METHODS
  PCa incidence and mortality was assessed for each category of clinical BPH using Kaplan-Meier plots of cumulative incidence and Cox proportional hazard ratios (HRs) adjusted for potential confounders.
  
  
  CONCLUSIONS
  For the entire cohort studies, multivariate-adjusted HRs for PCa incidence were 2.22 (95% confidence interval, 2.13-2.31) in men hospitalized and 3.26 (3.03-3.50) in men operated on for clinical BPH versus general population controls. Corresponding HRs for PCa mortality were 2.00 (1.91-2.08) for hospitalization and 7.85 (7.40-8.32) for surgery. For age-matched cohort studies, corresponding HRs for PCa incidence were 3.04 (2.96-3.13) for hospitalization, 2.60 (2.47-2.73) for surgery, 4.49 (4.33-4.65) for α-adrenergic receptor antagonist use, and 2.54 (2.40-2.68) for 5-ARI use. Each category of clinical BPH has limitations, but limitations differ between the categories and therefore are unlikely to explain the results.
  
  
  CONCLUSIONS
  In Danish men followed for up to 27 yr, clinical BPH was associated with a two- to three-fold increased risk of PCa incidence and with a two- to eight-fold increased risk of PCa mortality. These data should not be used to infer causality.
authors.affiliation: Department of Clinical Biochemistry, Herlev Hospital, Copenhagen University Hospital, Faculty of Health Sciences, University of Copenhagen, Denmark.
authors.forename: David D
authors.initials: DD
authors.lastname: Ørsted
authors.forename: Stig E
authors.initials: SE
authors.lastname: Bojesen
authors.forename: Sune F
authors.initials: SF
authors.lastname: Nielsen
authors.forename: Børge G
authors.initials: BG
authors.lastname: Nordestgaard
mesh_terms: D058891:5-alpha Reductase Inhibitors / Q000627:therapeutic use; D000317:Adrenergic alpha-Antagonists / Q000627:therapeutic use; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015331:Cohort Studies; D003718:Denmark / Q000453:epidemiology; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D011467:Prostate / Q000187:drug effects / Q000601:surgery; D011468:Prostatectomy / Q000706:statistics & numerical data; D011470:Prostatic Hyperplasia / Q000188:drug therapy / Q000401:mortality* / Q000601:surgery; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000401:mortality* / Q000601:surgery; D012042:Registries / Q000706:statistics & numerical data; D016896:Treatment Outcome
chemical_list: D058891:5-alpha Reductase Inhibitors; D000317:Adrenergic alpha-Antagonists