title: Aspirin, NSAIDs, and risk of prostate cancer: results from the REDUCE study.
abstract: OBJECTIVE
  A recent meta-analysis showed that aspirin was associated with reduced prostate cancer risk. As anti-inflammatory medications lower PSA levels, whether these findings reflect reduced prostate cancer detection or lower prostate cancer risk is unknown. We tested the association between aspirin and nonaspirin NSAID use on prostate cancer diagnosis in REDUCE, where all men received biopsies at 2 and 4 years largely independent of PSA. REDUCE tested dutasteride for prostate cancer risk reduction in men with a PSA of 2.5 to 10.0 ng/mL and a negative prestudy biopsy.
  
  
  METHODS
  We examined the association between aspirin, NSAIDs, or both and total, low-grade (Gleason < 7), or high-grade (Gleason ≥ 7) prostate cancer versus no prostate cancer using multinomial logistic regression among 6,390 men who underwent ≥1 on-study biopsy. Multivariable analyses were adjusted for age, race, geographic region, PSA, prostate volume, digital rectal examination, body mass index, treatment arm, smoking, alcohol, statins, hypertension, diabetes, and cardiovascular disease.
  
  
  RESULTS
  Overall, 3,169 men (50%) were nonusers, 1,368 (21%) used aspirin, 1,176 (18%) used NSAIDs, and 677 (11%) used both. In unadjusted models, aspirin was associated with reduced prostate cancer risk (OR = 0.85, P = 0.036). In multivariable analyses, aspirin was associated with reduced total prostate cancer risk (OR = 0.81, P = 0.015). Use of NSAIDs or NSAIDs and aspirin was not associated with total, low-grade, or high-grade prostate cancer, though all ORs were <1 (all P ≥ 0.08). Therefore, we created a dichotomous variable of aspirin and/or NSAID users versus nonusers. On multivariable analysis, the use of aspirin and/or NSAIDs was significantly associated with decreased total (OR = 0.87, P = 0.030) and high-grade (OR = 0.80, P = 0.040), but not with low-grade, prostate cancer risk (OR = 0.90, P = 0.15). Results were similar in placebo and dutasteride arms.
  
  
  CONCLUSIONS
  Among men with a negative biopsy, aspirin and/or NSAID use was associated with decreased prostate cancer risk. Additional studies are warranted.
authors.affiliation: Duke Prostate Center, Department of Surgery, Division of Urology, Duke University School of Medicine, Durham, North Carolina. Surgery Section, Durham VA Medical Center, Durham, North Carolina. Adriana.vidal@duke.edu.
authors.forename: Adriana C
authors.initials: AC
authors.lastname: Vidal
authors.affiliation: Duke Prostate Center, Department of Surgery, Division of Urology, Duke University School of Medicine, Durham, North Carolina. Surgery Section, Durham VA Medical Center, Durham, North Carolina.
authors.forename: Lauren E
authors.initials: LE
authors.lastname: Howard
authors.affiliation: Department of Urology, Mayo Clinic, Rochester, MN.
authors.forename: Daniel M
authors.initials: DM
authors.lastname: Moreira
authors.affiliation: GlaxoSmithKline Inc., Metabolic Pathways and Cardiovascular R&D Unit, King of Prussia, Pennsylvania.
authors.forename: Ramiro
authors.initials: R
authors.lastname: Castro-Santamaria
authors.affiliation: Washington University School of Medicine in St. Louis, St. Louis, Missouri.
authors.forename: Gerald L
authors.initials: GL
authors.lastname: Andriole
authors.affiliation: Duke Prostate Center, Department of Surgery, Division of Urology, Duke University School of Medicine, Durham, North Carolina. Surgery Section, Durham VA Medical Center, Durham, North Carolina. Department of Pathology, Duke University School of Medicine, Durham, North Carolina.
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Freedland
mesh_terms: D058891:5-alpha Reductase Inhibitors / Q000627:therapeutic use; D000368:Aged; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D001241:Aspirin / Q000494:pharmacology*; D004311:Double-Blind Method; D000068538:Dutasteride / Q000627:therapeutic use; D006801:Humans; D008297:Male; D008875:Middle Aged; D017430:Prostate-Specific Antigen; D011471:Prostatic Neoplasms / Q000453:epidemiology* / Q000473:pathology / Q000517:prevention & control; D012307:Risk Factors
chemical_list: D058891:5-alpha Reductase Inhibitors; D000894:Anti-Inflammatory Agents, Non-Steroidal; D017430:Prostate-Specific Antigen; D000068538:Dutasteride; D001241:Aspirin