title: Vitamin D receptor protein expression in tumor tissue and prostate cancer progression.
abstract: OBJECTIVE
  Data suggest that circulating 25-hydroxyvitamin D [25(OH)D] interacts with the vitamin D receptor (VDR) to decrease proliferation and increase apoptosis for some malignancies, although evidence for prostate cancer is less clear. How VDR expression in tumor tissue may influence prostate cancer progression has not been evaluated in large studies.
  
  
  METHODS
  We examined protein expression of VDR in tumor tissue among 841 patients with prostate cancer in relation to risk of lethal prostate cancer within two prospective cohorts, the Physicians' Health Study and Health Professionals Follow-Up Study. We also examined the association of VDR expression with prediagnostic circulating 25(OH)D and 1,25-dihydroxyvitamin D levels and with two VDR single nucleotide polymorphisms, FokI and BsmI.
  
  
  RESULTS
  Men whose tumors had high VDR expression had significantly lower prostate-specific antigen (PSA) at diagnosis (P for trend < .001), lower Gleason score (P for trend < .001), and less advanced tumor stage (P for trend < .001) and were more likely to have tumors harboring the TMPRSS2:ERG fusion (P for trend = .009). Compared with the lowest quartile, men whose tumors had the highest VDR expression had significantly reduced risk of lethal prostate cancer (hazard ratio [HR], 0.17; 95% CI, 0.07 to 0.41). This association was only slightly attenuated after adjustment for Gleason score and PSA at diagnosis (HR, 0.33; 95% CI, 0.13 to 0.83) or, additionally, for tumor stage (HR, 0.37; 95% CI, 0.14 to 0.94). Neither prediagnostic plasma vitamin D levels nor VDR polymorphisms were associated with VDR expression.
  
  
  CONCLUSIONS
  High VDR expression in prostate tumors is associated with a reduced risk of lethal cancer, suggesting a role of the vitamin D pathway in prostate cancer progression.
authors.affiliation: Department of Nutrition, Harvard School of Public Health, 655 Huntington Ave, Boston, MA 02115, USA.
authors.forename: Whitney K
authors.initials: WK
authors.lastname: Hendrickson
authors.forename: Richard
authors.initials: R
authors.lastname: Flavin
authors.forename: Julie L
authors.initials: JL
authors.lastname: Kasperzyk
authors.forename: Michelangelo
authors.initials: M
authors.lastname: Fiorentino
authors.forename: Fang
authors.initials: F
authors.lastname: Fang
authors.forename: Rosina
authors.initials: R
authors.lastname: Lis
authors.forename: Christopher
authors.initials: C
authors.lastname: Fiore
authors.forename: Kathryn L
authors.initials: KL
authors.lastname: Penney
authors.forename: Jing
authors.initials: J
authors.lastname: Ma
authors.forename: Philip W
authors.initials: PW
authors.lastname: Kantoff
authors.forename: Meir J
authors.initials: MJ
authors.lastname: Stampfer
authors.forename: Massimo
authors.initials: M
authors.lastname: Loda
authors.forename: Lorelei A
authors.initials: LA
authors.lastname: Mucci
authors.forename: Edward
authors.initials: E
authors.lastname: Giovannucci
mesh_terms: D000368:Aged; D018450:Disease Progression; D006801:Humans; D015994:Incidence; D008297:Male; D015514:Oncogene Proteins, Fusion / Q000235:genetics; D011446:Prospective Studies; D017430:Prostate-Specific Antigen / Q000097:blood; D011471:Prostatic Neoplasms / Q000737:chemistry* / Q000453:epidemiology / Q000473:pathology; D018167:Receptors, Calcitriol / Q000032:analysis*; D014807:Vitamin D / Q000031:analogs & derivatives / Q000097:blood
chemical_list: D015514:Oncogene Proteins, Fusion; D018167:Receptors, Calcitriol; C515553:TMPRSS2-ERG fusion protein, human; D014807:Vitamin D; C104450:25-hydroxyvitamin D; D017430:Prostate-Specific Antigen