title: Pre-diagnostic circulating sex hormone levels and risk of prostate cancer by ERG tumour protein expression.
abstract: BACKGROUND
  Experimental studies have shown androgen receptor stimulation to facilitate formation of the TMPRSS2:ERG gene fusion in prostate cell lines. No study has tested whether higher pre-diagnostic circulating sex hormone levels in men increase risk of developing TMPRSS2:ERG-positive prostate cancer specifically.
  
  
  METHODS
  We conducted a nested case-control study of 200 prostate cancer cases and 1057 controls from the Physicians' Health Study and Health Professionals Follow-up Study. We examined associations between pre-diagnostic circulating levels of total testosterone, free testosterone, DHT, androstanediol glucuronide, estradiol, and SHBG and risk of prostate cancer by TMPRSS2:ERG status. TMPRSS2:ERG was estimated by ERG immunohistochemistry. We used multivariable unconditional polytomous logistic regression to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for risk of ERG-positive (n=94) and, separately, ERG-negative (n=106) disease.
  
  
  RESULTS
  Free testosterone was significantly associated with the risk of ERG-positive prostate cancer (OR: 1.37, 95% CI: 1.05-1.77), but not ERG-negative prostate cancer (OR: 1.09, 95% CI: 0.86-1.38) (Pdiff=0.17). None of the remaining hormones evaluated showed clear differential associations with ERG-positive vs ERG-negative disease.
  
  
  CONCLUSIONS
  These findings provide some suggestive evidence that higher pre-diagnostic free testosterone levels are associated with an increased risk of developing TMPRSS2:ERG-positive prostate cancer.
authors.affiliation: Department of Epidemiology, Harvard T.H. Chan School of Public Health, 677 Huntington Avenue, Boston, MA 02115, USA.|Department of Epidemiology & Biostatistics, University of California San Francisco, 1450 3rd Street, San Francisco, CA 94158, USA.
authors.forename: Rebecca E
authors.initials: RE
authors.lastname: Graff
authors.affiliation: Department of Biostatistics, University of Washington, 1959 Northeast Pacific Street, Seattle, WA 98195, USA.
authors.forename: Allison
authors.initials: A
authors.lastname: Meisner
authors.affiliation: Department of Epidemiology, Harvard T.H. Chan School of Public Health, 677 Huntington Avenue, Boston, MA 02115, USA.
authors.forename: Thomas U
authors.initials: TU
authors.lastname: Ahearn
authors.affiliation: Department of Epidemiology, Harvard T.H. Chan School of Public Health, 677 Huntington Avenue, Boston, MA 02115, USA.|Center for Molecular Oncologic Pathology, Dana-Farber Cancer Institute, 450 Brookline Avenue, Boston, MA 02115, USA.|Pathology Unit, Addarii Institute, S. Orsola-Malpighi Hospital, Via Pietro Albertoni, 15, 40138 Bologna, Italy.
authors.forename: Michelangelo
authors.initials: M
authors.lastname: Fiorentino
authors.affiliation: Center for Molecular Oncologic Pathology, Dana-Farber Cancer Institute, 450 Brookline Avenue, Boston, MA 02115, USA.|Department of Pathology, Brigham and Women's Hospital, 75 Francis Street, Boston, MA 02115, USA.
authors.forename: Massimo
authors.initials: M
authors.lastname: Loda
authors.affiliation: Department of Epidemiology, Harvard T.H. Chan School of Public Health, 677 Huntington Avenue, Boston, MA 02115, USA.|Channing Division of Network Medicine, Brigham and Women's Hospital, Harvard Medical School, 181 Longwood Avenue, Boston, MA 02115, USA.|Department of Nutrition, Harvard T.H. Chan School of Public Health, 677 Huntington Avenue, Boston, MA 02115, USA.
authors.forename: Edward L
authors.initials: EL
authors.lastname: Giovannucci
authors.affiliation: Department of Epidemiology, Harvard T.H. Chan School of Public Health, 677 Huntington Avenue, Boston, MA 02115, USA.|Channing Division of Network Medicine, Brigham and Women's Hospital, Harvard Medical School, 181 Longwood Avenue, Boston, MA 02115, USA.
authors.forename: Lorelei A
authors.initials: LA
authors.lastname: Mucci
authors.affiliation: Department of Epidemiology, Harvard T.H. Chan School of Public Health, 677 Huntington Avenue, Boston, MA 02115, USA.|Clinical Epidemiology Unit, Department of Medicine Solna, Karolinska Institutet, SE-171 77 Stockholm, Sweden.
authors.forename: Andreas
authors.initials: A
authors.lastname: Pettersson
mesh_terms: D016022:Case-Control Studies; D004958:Estradiol / Q000097:blood; D005500:Follow-Up Studies; D012739:Gonadal Steroid Hormones / Q000097:blood*; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D011446:Prospective Studies; D011471:Prostatic Neoplasms / Q000097:blood* / Q000175:diagnosis* / Q000473:pathology; D011944:Receptors, Androgen / Q000378:metabolism; D012306:Risk; D012697:Serine Endopeptidases / Q000378:metabolism; D013739:Testosterone / Q000097:blood; D015534:Trans-Activators / Q000378:metabolism*; D000071230:Transcriptional Regulator ERG
chemical_list: C410798:AR protein, human; C072312:ERG protein, human; D012739:Gonadal Steroid Hormones; D011944:Receptors, Androgen; D015534:Trans-Activators; D000071230:Transcriptional Regulator ERG; D013739:Testosterone; D004958:Estradiol; D012697:Serine Endopeptidases; C421305:TMPRSS2 protein, human