title: Prognostic significance of vitamin D receptor polymorphisms in head and neck squamous cell carcinoma.
abstract: BACKGROUND
  In patients with advanced non-small-cell lung cancer, vitamin D receptor (VDR) polymorphisms and haplotypes are reported to be associated with survival. We hypothesized that a similar association would be observed in patients with head and neck squamous-cell carcinoma (HNSCC).
  
  
  METHODS
  In a post-hoc analysis of our previous prospective cohort study, VDR polymorphisms including Cdx2 G/A (rs11568820), FokI C/T (rs10735810), BsmI A/G (rs1544410), ApaI G/T (rs7976091), and TaqI T/C (rs731236) were genotyped by sequencing in 204 consecutive patients with HNSCC who underwent tumor resection. Progression-free survival was compared between VDR polymorphisms using Kaplan-Meier survival curves with log-rank tests and Cox proportional hazard models adjusting for age, gender, smoking status, primary tumor sites, postoperative stages, existence of residual tumor, and postoperative treatment with chemotherapy or radiotherapy.
  
  
  RESULTS
  During a median follow-up of 1,047 days, tumor progression and death occurred in 76 (37.3%) and 27 (13.2%) patients, respectively. The FokI T/T genotype was associated with poor progression-free survival: median survival for T/T was 265 days compared with 1,127 days for C/C or C/T (log-rank test: P = 0.0004; adjusted hazard ratio, 3.03; 95% confidence interval, 1.62 to 5.67; P = 0.001). In contrast, the other polymorphisms (Cdx2, BsmI, ApaI, TaqI) showed no significant association with progression-free survival. The A-T-G (Cdx2-FokI-ApaI) haplotype demonstrated a significant association with a higher progression rate (P = 0.02).
  
  
  CONCLUSIONS
  These results suggest that VDR polymorphisms and haplotypes may be associated with prognosis in patients with HNSCC, although the sample size is not large enough to draw definitive conclusions.
authors.affiliation: Division of Molecular Epidemiology, Jikei University School of Medicine, Tokyo, Japan.
authors.forename: Takanori
authors.initials: T
authors.lastname: Hama
authors.forename: Chihiro
authors.initials: C
authors.lastname: Norizoe
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Suga
authors.forename: Takeshi
authors.initials: T
authors.lastname: Mimura
authors.forename: Takakuni
authors.initials: T
authors.lastname: Kato
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Moriyama
authors.forename: Mitsuyoshi
authors.initials: M
authors.lastname: Urashima
mesh_terms: D000483:Alleles; D002294:Carcinoma, Squamous Cell / Q000175:diagnosis* / Q000235:genetics*; D018572:Disease-Free Survival; D005260:Female; D020022:Genetic Predisposition to Disease; D006239:Haplotypes / Q000235:genetics; D006258:Head and Neck Neoplasms / Q000175:diagnosis* / Q000235:genetics*; D006801:Humans; D053208:Kaplan-Meier Estimate; D015810:Linkage Disequilibrium / Q000235:genetics; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011379:Prognosis; D016016:Proportional Hazards Models; D018167:Receptors, Calcitriol / Q000235:genetics*; D000077195:Squamous Cell Carcinoma of Head and Neck
chemical_list: D018167:Receptors, Calcitriol