title: Oxidative stress measured by urine F2-isoprostane level is associated with prostate cancer.
abstract: OBJECTIVE
  Oxidative stress is implicated in prostate cancer by several lines of evidence. We studied the relationship between the level of F2-isoprostanes, a validated biomarker of oxidative stress, and prostate cancer and high grade prostatic intraepithelial neoplasia.
  
  
  METHODS
  This case-control analysis within the Nashville Men's Health Study included men recruited at prostate biopsy. Body morphometrics, health history and urine were collected from more than 2,000 men before biopsy. F2-isoprostanes were measured by gas chromatography/mass spectrometry within an age matched sample of Nashville Men's Health Study participants that included 140 patients with high grade prostatic intraepithelial neoplasia, 160 biopsy negative controls and 200 prostate cancer cases. Multivariable linear and logistic regression was used to determine the associations between F2-isoprostane level, and high grade prostatic intraepithelial neoplasia and prostate cancer.
  
  
  RESULTS
  Mean patient age was 66.9 years (SD 7.2) and 10.1% were nonwhite. Adjusted geometric mean F2-isoprostane levels were higher in patients with prostate cancer (1.82, 95% CI 1.66-2.00) or high grade prostatic intraepithelial neoplasia (1.82, 95% CI 1.68-1.96) than in controls (1.63, 95% CI 1.49-1.78, p <0.001), but were similar across Gleason scores (p = 0.511). The adjusted odds of high grade prostatic intraepithelial neoplasia and prostate cancer increased with increasing F2-isoprostane quartile (p-trend = 0.015 and 0.047, respectively) and the highest F2-isoprostane quartile was associated with significantly increased odds of prostate cancer (OR 2.44, 95% CI 1.17-5.09, p = 0.017).
  
  
  CONCLUSIONS
  Pre-diagnosis urine F2-isoprostane level is increased in men with high grade prostatic intraepithelial neoplasia or prostate cancer, suggesting urinary F2-isoprostane provides a biomarker for the role for oxidative stress in prostate carcinogenesis. F2-isoprostanes may also serve to estimate the efficacy of interventions targeting oxidative stress mechanisms in prostate cancer prevention or treatment.
authors.affiliation: Department of Urologic Surgery, Vanderbilt University Medical Center, Nashville, Tennessee 37203, USA. Dan.barocas@vanderbilt.edu
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Barocas
authors.forename: Saundra
authors.initials: S
authors.lastname: Motley
authors.forename: Michael S
authors.initials: MS
authors.lastname: Cookson
authors.forename: Sam S
authors.initials: SS
authors.lastname: Chang
authors.forename: David F
authors.initials: DF
authors.lastname: Penson
authors.forename: Qi
authors.initials: Q
authors.lastname: Dai
authors.forename: Ginger
authors.initials: G
authors.lastname: Milne
authors.forename: L Jackson
authors.initials: LJ
authors.lastname: Roberts
authors.forename: Jason
authors.initials: J
authors.lastname: Morrow
authors.forename: Raoul S
authors.initials: RS
authors.lastname: Concepcion
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Smith
authors.forename: Jay H
authors.initials: JH
authors.lastname: Fowke
mesh_terms: D000368:Aged; D016022:Case-Control Studies; D028441:F2-Isoprostanes / Q000652:urine*; D006801:Humans; D008297:Male; D018384:Oxidative Stress; D019048:Prostatic Intraepithelial Neoplasia / Q000378:metabolism / Q000652:urine*; D011471:Prostatic Neoplasms / Q000378:metabolism / Q000652:urine*
chemical_list: D028441:F2-Isoprostanes