title: Sex steroid hormone metabolism in relation to risk of aggressive prostate cancer.
abstract: BACKGROUND
  The combined action of androgens and estrogens-specifically their balance-may play a role in prostate carcinogenesis, but existing evidence is sparse and inconsistent. We investigated associations between serum sex steroid hormones, including estrogen metabolites, and risk of aggressive prostate cancer.
  
  
  METHODS
  In a case-control study nested within the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial cohort, we measured serum estrone, estradiol, and 13 estrogen metabolites, in the 2-, 4-, or 16-hydroxylation pathways, using an LC/MS-MS assay. Cases (n = 195) were non-Hispanic white men ages 55 to 70 years when diagnosed with aggressive prostate cancer (stage III or IV and/or Gleason ≥7). Controls (n = 195) were non-Hispanic white men without prostate cancer who were frequency matched to cases by age and year at blood draw, and time since baseline screen. Only men with serum testosterone and sex hormone-binding globulin measured previously were eligible. Logistic regression models were used to estimate ORs and 95% confidence intervals (95% CI).
  
  
  RESULTS
  Risk of aggressive prostate cancer was strongly inversely associated with estradiol:testosterone ratio (OR4th quartile vs. 1st = 0.27; 95% CI, 0.12-0.59, Ptrend = 0.003) and positively associated with 2:16α-hydroxyestrone ratio (OR4th quartile vs. 1st = 2.44; 95% CI, 1.34-4.45, Ptrend = 0.001). Individual estrogen metabolites were unrelated to risk.
  
  
  CONCLUSIONS
  Our findings suggest that sex steroid hormones, specifically the estrogen-androgen balance, may be important in the development of aggressive prostate cancer.
  
  
  CONCLUSIONS
  Improved understanding of the hormonal etiology of prostate cancer is critical for prevention and therapeutic interventions.
authors.affiliation: Divisions of Cancer Epidemiology and Genetics and blacka@mail.nih.gov.
authors.forename: Amanda
authors.initials: A
authors.lastname: Black
authors.affiliation: Cancer Prevention, National Cancer Institute, NIH, DHHS, Rockville, Maryland.
authors.forename: Paul F
authors.initials: PF
authors.lastname: Pinsky
authors.affiliation: Washington University, St. Louis, Missouri.
authors.forename: Robert L
authors.initials: RL
authors.lastname: Grubb
authors.affiliation: Divisions of Cancer Epidemiology and Genetics and.
authors.forename: Roni T
authors.initials: RT
authors.lastname: Falk
authors.affiliation: Cancer Prevention Institute of California, Fremont, CA and Stanford Cancer Institute, Palo Alto, California.
authors.forename: Ann W
authors.initials: AW
authors.lastname: Hsing
authors.affiliation: Cancer Prevention Institute of California, Fremont, CA and Stanford Cancer Institute, Palo Alto, California.
authors.forename: Lisa
authors.initials: L
authors.lastname: Chu
authors.affiliation: Surgeon General of the Army, Pharmacovigilance Center, U.S. Army Medical Command, Falls Church, Virginia.
authors.forename: Tamra
authors.initials: T
authors.lastname: Meyer
authors.affiliation: C2N Diagnostics, Saint Louis, Missouri.
authors.forename: Timothy D
authors.initials: TD
authors.lastname: Veenstra
authors.affiliation: Cancer Research Technology Program, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, Maryland.
authors.forename: Xia
authors.initials: X
authors.lastname: Xu
authors.affiliation: Divisions of Cancer Epidemiology and Genetics and.
authors.forename: Kai
authors.initials: K
authors.lastname: Yu
authors.affiliation: Divisions of Cancer Epidemiology and Genetics and.
authors.forename: Regina G
authors.initials: RG
authors.lastname: Ziegler
authors.affiliation: Divisions of Cancer Epidemiology and Genetics and.
authors.forename: Louise A
authors.initials: LA
authors.lastname: Brinton
authors.affiliation: Divisions of Cancer Epidemiology and Genetics and.
authors.forename: Robert N
authors.initials: RN
authors.lastname: Hoover
authors.affiliation: Divisions of Cancer Epidemiology and Genetics and.
authors.forename: Michael B
authors.initials: MB
authors.lastname: Cook
mesh_terms: D000368:Aged; D016022:Case-Control Studies; D004958:Estradiol / Q000097:blood; D004967:Estrogens / Q000097:blood; D004970:Estrone / Q000097:blood; D012739:Gonadal Steroid Hormones / Q000097:blood*; D006801:Humans; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D011471:Prostatic Neoplasms / Q000097:blood* / Q000209:etiology / Q000473:pathology*; D016032:Randomized Controlled Trials as Topic; D013739:Testosterone / Q000097:blood
chemical_list: D004967:Estrogens; D012739:Gonadal Steroid Hormones; D004970:Estrone; D013739:Testosterone; D004958:Estradiol