title: Agent Orange as a risk factor for high-grade prostate cancer.
abstract: BACKGROUND
  Agent Orange (AO) exposure (AOe) is a potential risk factor for the development of prostate cancer (PCa). However, it is unknown whether AOe specifically increases the risk of lethal PCa. The objective of this study was to determine the association between AOe and the risk of detecting high-grade PCa (HGPCa) (Gleason score ≥7) on biopsy in a US Veteran cohort.
  
  
  METHODS
  Risk factors included clinicodemographic and laboratory data from veterans who were referred for an initial prostate biopsy. Outcomes were defined as the presence versus the absence of PCa, HGPCa, or low-grade PCa (LGPCa) (Gleason score ≤6) in biopsy specimens. Risk among AOe veterans relative to unexposed veterans was estimated using multivariate logistic regression. Separate models were used to determine whether AOe was associated with an increased risk of PCa, HGPCa, or LGPCa.
  
  
  RESULTS
  Of 2720 veterans who underwent biopsy, PCa was diagnosed in 896 veterans (32.9%), and 459 veterans (16.9%) had HGPCa. AOe was associated with a 52% increase in the overall risk of detecting PCa (adjusted odds ratio, 1.52; 95% confidence interval, 1.07-2.13). AOe did not confer an increase in the risk of LGPCa (adjusted odds ratio, 1.24; 95% confidence interval, 0.81-1.91), although a 75% increase in the risk of HGPCa was observed (adjusted odds ratio, 1.75; 95% confidence interval, 1.12-2.74). AOe was associated with a 2.1-fold increase (95% confidence interval, 1.22-3.62; P < .01) in the risk of detecting PCa with a Gleason score ≥8.
  
  
  CONCLUSIONS
  The current results indicated that an increased risk of PCa associated with AOe is driven by an increased risk of HGPCa in men who undergo an initial prostate biopsy. These findings may aid in improved PCa screening for Vietnam-era veterans.
authors.affiliation: Public Health and Preventive Medicine, Oregon Health and Science University, Portland, Oregon, USA.
authors.forename: Nathan
authors.initials: N
authors.lastname: Ansbaugh
authors.forename: Jackilen
authors.initials: J
authors.lastname: Shannon
authors.forename: Motomi
authors.initials: M
authors.lastname: Mori
authors.forename: Paige E
authors.initials: PE
authors.lastname: Farris
authors.forename: Mark
authors.initials: M
authors.lastname: Garzotto
mesh_terms: D015085:2,4,5-Trichlorophenoxyacetic Acid / Q000633:toxicity*; D015084:2,4-Dichlorophenoxyacetic Acid / Q000633:toxicity*; D000368:Aged; D000369:Aged, 80 and over; D000075182:Agent Orange; D001707:Biopsy, Needle; D002273:Carcinogens / Q000633:toxicity*; D006801:Humans; D016015:Logistic Models; D008297:Male; D015999:Multivariate Analysis; D060787:Neoplasm Grading; D016017:Odds Ratio; D000072317:Polychlorinated Dibenzodioxins / Q000633:toxicity*; D017430:Prostate-Specific Antigen / Q000097:blood; D011471:Prostatic Neoplasms / Q000139:chemically induced* / Q000453:epidemiology / Q000473:pathology*; D018570:Risk Assessment; D012307:Risk Factors; D014481:United States / Q000453:epidemiology; D014728:Veterans / Q000706:statistics & numerical data*; D047829:Vietnam Conflict
chemical_list: D002273:Carcinogens; D000072317:Polychlorinated Dibenzodioxins; D015084:2,4-Dichlorophenoxyacetic Acid; D000075182:Agent Orange; D015085:2,4,5-Trichlorophenoxyacetic Acid; D017430:Prostate-Specific Antigen