title: The impact of vitamin D pathway genetic variation and circulating 25-hydroxyvitamin D on cancer outcome: systematic review and meta-analysis.
abstract: BACKGROUND
  Vitamin D has been linked with improved cancer outcome. This systematic review and meta-analysis investigates the relationship between cancer outcomes and both vitamin D-related genetic variation and circulating 25-hydroxyvitamin D (25OHD) concentration.
  
  
  METHODS
  A systematic review and meta-analysis of papers until November 2016 on PubMed, EMBASE and Web of Science pertaining to association between circulating vitamin D level, functionally relevant vitamin D receptor genetic variants and variants within vitamin D pathway genes and cancer survival or disease progression was performed.
  
  
  RESULTS
  A total of 44 165 cases from 64 studies were included in meta-analyses. Higher 25OHD was associated with better overall survival (hazard ratio (HR=0.74, 95% CI: 0.66-0.82) and progression-free survival (HR=0.84, 95% CI: 0.77-0.91). The rs1544410 (BsmI) variant was associated with overall survival (HR=1.40, 95% CI: 1.05-1.75) and rs7975232 (ApaI) with progression-free survival (HR=1.29, 95% CI: 1.02-1.56). The rs2228570 (FokI) variant was associated with overall survival in lung cancer patients (HR=1.29, 95% CI: 1.0-1.57), with a suggestive association across all cancers (HR=1.26, 95% CI: 0.96-1.56).
  
  
  CONCLUSIONS
  Higher 25OHD concentration is associated with better cancer outcome, and the observed association of functional variants in vitamin D pathway genes with outcome supports a causal link. This analysis provides powerful background rationale to instigate clinical trials to investigate the potential beneficial effect of vitamin D in the context of stratification by genotype.
authors.affiliation: MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh EH42XU, UK.
authors.forename: P G
authors.initials: PG
authors.lastname: Vaughan-Shaw
authors.affiliation: Department of Public Health and Primary Care, Trinity College Dublin, Dublin 24, Republic of Ireland.
authors.forename: F
authors.initials: F
authors.lastname: O'Sullivan
authors.affiliation: MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh EH42XU, UK.
authors.forename: S M
authors.initials: SM
authors.lastname: Farrington
authors.affiliation: MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh EH42XU, UK.|Centre for Population Health Sciences, University of Edinburgh, Edinburgh EH164UX, UK.
authors.forename: E
authors.initials: E
authors.lastname: Theodoratou
authors.affiliation: MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh EH42XU, UK.|Centre for Population Health Sciences, University of Edinburgh, Edinburgh EH164UX, UK.
authors.forename: H
authors.initials: H
authors.lastname: Campbell
authors.affiliation: MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh EH42XU, UK.
authors.forename: M G
authors.initials: MG
authors.lastname: Dunlop
authors.affiliation: Department of Public Health and Primary Care, Trinity College Dublin, Dublin 24, Republic of Ireland.
authors.forename: L
authors.initials: L
authors.lastname: Zgaga
mesh_terms: D020022:Genetic Predisposition to Disease; D014644:Genetic Variation / Q000235:genetics*; D006801:Humans; D009369:Neoplasms / Q000097:blood* / Q000235:genetics*; D011379:Prognosis; D018167:Receptors, Calcitriol / Q000235:genetics*; D014807:Vitamin D / Q000031:analogs & derivatives* / Q000097:blood
chemical_list: D018167:Receptors, Calcitriol; C579457:VDR protein, human; D014807:Vitamin D; C104450:25-hydroxyvitamin D