title: Urinary estrogen metabolites and prostate cancer: a case-control study in the United States.
abstract: OBJECTIVE
  To analyze the association of prostate cancer risk with estrogen metabolism, expressed as the ratio of 2-hydroxyestrone (2-OHE1) to 16alpha-hydroxyestrone (16alpha-OHE1), in a case-control study conducted in Buffalo, NY, between 1998 and 2001.
  
  
  METHODS
  One hundred and thirteen men, aged 45-85 years, with incident, primary pathologically confirmed prostate cancer were enrolled in the study; 317 residence-matched controls were also enrolled. Cases were enrolled and the specimens collected before starting any therapy. To exclude latent prostate carcinomas, the present study included only patients with clinically apparent disease (stage B and higher). Prostate cancer cases and control subjects were excluded if on hormonal treatment, or affected with metabolic or endocrine diseases. Control subjects with a prostate-specific antigen (PSA) value higher than 4 ng/ml were excluded from the control group. Urine was used for the determinations of 2-OHE1 and 16alpha-OHE1. Age, race, body weight, waist-to-hip ratio, and smoking were analyzed as possible confounders.
  
  
  RESULTS
  Althpugh the results were not statistically significant, elevated 2-OHE1 urinary levels suggested a reduced prostate cancer risk: men in the highest tertile had an adjusted odds ratio (OR) for prostate cancer of 0.83 (95% confidence interval (CI) 0.43-1.44). Conversely, elevated 16alpha-OHE1 urinary levels were associated with an increased risk of prostate cancer: the highest tertile had an adjusted OR for prostate cancer of 1.69 (95% CI 0.93-3.06, p for linear trend = 0.02). Finally, the 2-OHE1 to 16alpha-OHE1 ratio was associated with a reduced risk of prostate cancer with an OR of 0.61 (95% CI 0.33-1.15, p for linear trend = 0.04).
  
  
  CONCLUSIONS
  Results of this case-control study suggest that the estrogen metabolic pathway favoring 2-hydroxylation over 16alpha-hydroxylation may reduce risk of clinically evident prostate cancer.
authors.affiliation: Department of Social and Preventive Medicine, University at Buffalo, State University of New York, NY, USA. muti@buffalo.edu
authors.forename: Paola
authors.initials: P
authors.lastname: Muti
authors.forename: Kim
authors.initials: K
authors.lastname: Westerlind
authors.forename: Tiejian
authors.initials: T
authors.lastname: Wu
authors.forename: Thomas
authors.initials: T
authors.lastname: Grimaldi
authors.forename: John
authors.initials: J
authors.lastname: De Berry
authors.forename: Holger
authors.initials: H
authors.lastname: Schünemann
authors.forename: Jo L
authors.initials: JL
authors.lastname: Freudenheim
authors.forename: Helyn
authors.initials: H
authors.lastname: Hill
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Carruba
authors.forename: Leon
authors.initials: L
authors.lastname: Bradlow
mesh_terms: D000230:Adenocarcinoma / Q000453:epidemiology / Q000652:urine*; D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D006801:Humans; D006894:Hydroxyestrones / Q000652:urine*; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D009518:New York / Q000453:epidemiology; D011471:Prostatic Neoplasms / Q000453:epidemiology / Q000652:urine*; D012307:Risk Factors
chemical_list: D006894:Hydroxyestrones