title: Associations of circulating retinol, vitamin E, and 1,25-dihydroxyvitamin D with prostate cancer diagnosis, stage, and grade.
abstract: OBJECTIVE
  Some epidemiological studies suggest that vitamin A (retinol), vitamin E, and vitamin D (total 25-hydroxyvitamin D, 25(OH)D; 1,25-dihydroxyvitamin, 1,25(OH)(2)D) are protective against prostate cancer. However, the evidence is not conclusive, with positive and null associations reported for all three vitamins. Limitations of previous studies include small sample size, lack of population controls, and reliance on self-reported dietary intake. Few studies have explored the interactions of circulating 25(OH)D with 1,25(OH)(2)D or retinol, which are biologically plausible interactions.
  
  
  METHODS
  We investigated the associations of circulating retinol, vitamin E, and 1,25(OH)(2)D with PSA-detected prostate cancer risk, stage, and grade in a case-control study nested within the Prostate Testing for Cancer and Treatment (ProtecT) trial. We investigated the possibility of an interaction between 25(OH)D and 1,25(OH)(2)D and whether the previously observed association between 25(OH)D and prostate cancer may be modified by retinol levels.
  
  
  RESULTS
  We included 1,433 prostate cancer cases and 1,433 healthy controls. There was no evidence of associations of circulating retinol, vitamin E, or 1,25(OH)(2)D with overall prostate cancer risk, stage (advanced vs localized), or Gleason grade (high- (≥7) vs low (<7) grade). There was no evidence of an interaction of 1,25(OH)(2)D and 25(OH)D with prostate cancer risk, stage, or grade (p interaction ≥ 0.24). The association between 25(OH)D and prostate cancer did not differ by retinol level (p interaction = 0.34).
  
  
  CONCLUSIONS
  We found no evidence that retinol, vitamin E, or 1,25(OH)(2)D concentrations were associated with overall prostate cancer risk or more aggressive prostate cancer phenotypes. There was no evidence of an interaction between 25(OH)D and 1,25(OH)(2)D or retinol.
authors.affiliation: School of Social and Community Medicine, University of Bristol, Canynge Hall, 39 Whatley Road, Bristol BS8 2PS, UK. becky.gilbert@bristol.ac.uk
authors.forename: Rebecca
authors.initials: R
authors.lastname: Gilbert
authors.forename: Chris
authors.initials: C
authors.lastname: Metcalfe
authors.forename: William D
authors.initials: WD
authors.lastname: Fraser
authors.forename: Jenny
authors.initials: J
authors.lastname: Donovan
authors.forename: Freddie
authors.initials: F
authors.lastname: Hamdy
authors.forename: David E
authors.initials: DE
authors.lastname: Neal
authors.forename: J Athene
authors.initials: JA
authors.lastname: Lane
authors.forename: Richard M
authors.initials: RM
authors.lastname: Martin
mesh_terms: D016022:Case-Control Studies; D006801:Humans; D007610:Kallikreins / Q000097:blood; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D017430:Prostate-Specific Antigen / Q000097:blood; D011471:Prostatic Neoplasms / Q000097:blood* / Q000453:epidemiology / Q000473:pathology; D018570:Risk Assessment; D012307:Risk Factors; D006113:United Kingdom / Q000453:epidemiology; D014801:Vitamin A / Q000097:blood*; D014807:Vitamin D / Q000031:analogs & derivatives* / Q000097:blood; D014810:Vitamin E / Q000097:blood*
chemical_list: D014801:Vitamin A; D014807:Vitamin D; D014810:Vitamin E; C097949:1,25-dihydroxyvitamin D; C549870:KLK3 protein, human; D007610:Kallikreins; D017430:Prostate-Specific Antigen