title: Plasma vitamin D concentration influences survival outcome after a diagnosis of colorectal cancer.
abstract: OBJECTIVE
  We investigated whether the plasma level of 25-hydroxyvitamin D (25-OHD) after a diagnosis of colorectal cancer (CRC) influences survival outcome.
  
  
  METHODS
  We prospectively studied 1,598 patients with stage I to III CRC. We sought association between plasma 25-OHD and stage-specific survival and tested for interaction between 25-OHD level and variation at the vitamin D receptor (VDR) gene locus. Blood was sampled postoperatively, and plasma was assayed for 25-OHD by liquid chromatography-tandem mass spectrometry. VDR polymorphisms (rs1544410, rs10735810, rs7975232, rs11568820) were genotyped, and haplotypes were inferred by using BEAGLE software. We tested for association between survival and 25-OHD, VDR genotype/haplotype, and after applying a VDR genotype-25-OHD interaction term. We conducted Kaplan-Meier survival analysis and used Cox proportional hazards models to estimate adjusted hazard ratios (HRs).
  
  
  RESULTS
  We found strong associations between plasma 25-OHD concentration and CRC-specific (P = .008) and all-cause mortality (P = .003). Adjusted HRs were 0.68 (95% CI, 0.50 to 0.90) and 0.70 (95% CI, 0.55 to 0.89), respectively (highest v lowest 25-OHD tertile), particularly in stage II disease (HR, 0.44; P = .004 for CRC-specific mortality). We detected gene-environment interactions between 25-OHD concentration and rs11568820 genotype for CRC-specific (P = .008) and all-cause (P = .022) mortality, number of protective alleles (P = .004 and P = .018, respectively), and GAGC haplotype at the VDR locus for all-cause mortality (P = .008).
  
  
  CONCLUSIONS
  In patients with stage I to III CRC, postoperative plasma vitamin D is associated with clinically important differences in survival outcome, higher levels being associated with better outcome. We observed interactions between 25-OHD level and VDR genotype, suggesting a causal relationship between vitamin D and survival. The influence of vitamin D supplementation on CRC outcome will require further investigation.
authors.affiliation: Lina Zgaga, Susan M. Farrington, Farhat V.N. Din, Li Yin Ooi, Dominik Glodzik, Albert Tenesa, Harry Campbell, and Malcolm G. Dunlop, University of Edinburgh and Western General Hospital; Evropi Theodoratou and Harry Campbell, University of Edinburgh, Edinburgh; Albert Tenesa, University of Edinburgh, Roslin; Susan Johnston, Glasgow Royal Infirmary, Glasgow, United Kingdom; Lina Zgaga, Trinity College Dublin, Dublin, Ireland.
authors.forename: Lina
authors.initials: L
authors.lastname: Zgaga
authors.affiliation: Lina Zgaga, Susan M. Farrington, Farhat V.N. Din, Li Yin Ooi, Dominik Glodzik, Albert Tenesa, Harry Campbell, and Malcolm G. Dunlop, University of Edinburgh and Western General Hospital; Evropi Theodoratou and Harry Campbell, University of Edinburgh, Edinburgh; Albert Tenesa, University of Edinburgh, Roslin; Susan Johnston, Glasgow Royal Infirmary, Glasgow, United Kingdom; Lina Zgaga, Trinity College Dublin, Dublin, Ireland.
authors.forename: Evropi
authors.initials: E
authors.lastname: Theodoratou
authors.affiliation: Lina Zgaga, Susan M. Farrington, Farhat V.N. Din, Li Yin Ooi, Dominik Glodzik, Albert Tenesa, Harry Campbell, and Malcolm G. Dunlop, University of Edinburgh and Western General Hospital; Evropi Theodoratou and Harry Campbell, University of Edinburgh, Edinburgh; Albert Tenesa, University of Edinburgh, Roslin; Susan Johnston, Glasgow Royal Infirmary, Glasgow, United Kingdom; Lina Zgaga, Trinity College Dublin, Dublin, Ireland.
authors.forename: Susan M
authors.initials: SM
authors.lastname: Farrington
authors.affiliation: Lina Zgaga, Susan M. Farrington, Farhat V.N. Din, Li Yin Ooi, Dominik Glodzik, Albert Tenesa, Harry Campbell, and Malcolm G. Dunlop, University of Edinburgh and Western General Hospital; Evropi Theodoratou and Harry Campbell, University of Edinburgh, Edinburgh; Albert Tenesa, University of Edinburgh, Roslin; Susan Johnston, Glasgow Royal Infirmary, Glasgow, United Kingdom; Lina Zgaga, Trinity College Dublin, Dublin, Ireland.
authors.forename: Farhat V N
authors.initials: FV
authors.lastname: Din
authors.affiliation: Lina Zgaga, Susan M. Farrington, Farhat V.N. Din, Li Yin Ooi, Dominik Glodzik, Albert Tenesa, Harry Campbell, and Malcolm G. Dunlop, University of Edinburgh and Western General Hospital; Evropi Theodoratou and Harry Campbell, University of Edinburgh, Edinburgh; Albert Tenesa, University of Edinburgh, Roslin; Susan Johnston, Glasgow Royal Infirmary, Glasgow, United Kingdom; Lina Zgaga, Trinity College Dublin, Dublin, Ireland.
authors.forename: Li Yin
authors.initials: LY
authors.lastname: Ooi
authors.affiliation: Lina Zgaga, Susan M. Farrington, Farhat V.N. Din, Li Yin Ooi, Dominik Glodzik, Albert Tenesa, Harry Campbell, and Malcolm G. Dunlop, University of Edinburgh and Western General Hospital; Evropi Theodoratou and Harry Campbell, University of Edinburgh, Edinburgh; Albert Tenesa, University of Edinburgh, Roslin; Susan Johnston, Glasgow Royal Infirmary, Glasgow, United Kingdom; Lina Zgaga, Trinity College Dublin, Dublin, Ireland.
authors.forename: Dominik
authors.initials: D
authors.lastname: Glodzik
authors.affiliation: Lina Zgaga, Susan M. Farrington, Farhat V.N. Din, Li Yin Ooi, Dominik Glodzik, Albert Tenesa, Harry Campbell, and Malcolm G. Dunlop, University of Edinburgh and Western General Hospital; Evropi Theodoratou and Harry Campbell, University of Edinburgh, Edinburgh; Albert Tenesa, University of Edinburgh, Roslin; Susan Johnston, Glasgow Royal Infirmary, Glasgow, United Kingdom; Lina Zgaga, Trinity College Dublin, Dublin, Ireland.
authors.forename: Susan
authors.initials: S
authors.lastname: Johnston
authors.affiliation: Lina Zgaga, Susan M. Farrington, Farhat V.N. Din, Li Yin Ooi, Dominik Glodzik, Albert Tenesa, Harry Campbell, and Malcolm G. Dunlop, University of Edinburgh and Western General Hospital; Evropi Theodoratou and Harry Campbell, University of Edinburgh, Edinburgh; Albert Tenesa, University of Edinburgh, Roslin; Susan Johnston, Glasgow Royal Infirmary, Glasgow, United Kingdom; Lina Zgaga, Trinity College Dublin, Dublin, Ireland.
authors.forename: Albert
authors.initials: A
authors.lastname: Tenesa
authors.affiliation: Lina Zgaga, Susan M. Farrington, Farhat V.N. Din, Li Yin Ooi, Dominik Glodzik, Albert Tenesa, Harry Campbell, and Malcolm G. Dunlop, University of Edinburgh and Western General Hospital; Evropi Theodoratou and Harry Campbell, University of Edinburgh, Edinburgh; Albert Tenesa, University of Edinburgh, Roslin; Susan Johnston, Glasgow Royal Infirmary, Glasgow, United Kingdom; Lina Zgaga, Trinity College Dublin, Dublin, Ireland.
authors.forename: Harry
authors.initials: H
authors.lastname: Campbell
authors.affiliation: Lina Zgaga, Susan M. Farrington, Farhat V.N. Din, Li Yin Ooi, Dominik Glodzik, Albert Tenesa, Harry Campbell, and Malcolm G. Dunlop, University of Edinburgh and Western General Hospital; Evropi Theodoratou and Harry Campbell, University of Edinburgh, Edinburgh; Albert Tenesa, University of Edinburgh, Roslin; Susan Johnston, Glasgow Royal Infirmary, Glasgow, United Kingdom; Lina Zgaga, Trinity College Dublin, Dublin, Ireland. malcolm.dunlop@igmm.ed.ac.uk.
authors.forename: Malcolm G
authors.initials: MG
authors.lastname: Dunlop
mesh_terms: D016022:Case-Control Studies; D015179:Colorectal Neoplasms / Q000097:blood* / Q000235:genetics / Q000401:mortality* / Q000473:pathology; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011110:Polymorphism, Genetic; D011446:Prospective Studies; D018167:Receptors, Calcitriol / Q000235:genetics; D012307:Risk Factors; D012606:Scotland / Q000453:epidemiology; D014807:Vitamin D / Q000031:analogs & derivatives* / Q000097:blood / Q000378:metabolism
chemical_list: D018167:Receptors, Calcitriol; C579457:VDR protein, human; D014807:Vitamin D; C104450:25-hydroxyvitamin D