Prognostic significance of vitamin D receptor polymorphisms in head and neck squamous cell carcinoma

PLoS One. 2011;6(12):e29634. doi: 10.1371/journal.pone.0029634. Epub 2011 Dec 29.


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).

Conclusion: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alleles
  • Carcinoma, Squamous Cell / diagnosis*
  • Carcinoma, Squamous Cell / genetics*
  • Disease-Free Survival
  • Female
  • Genetic Predisposition to Disease*
  • Haplotypes / genetics
  • Head and Neck Neoplasms / diagnosis*
  • Head and Neck Neoplasms / genetics*
  • Humans
  • Kaplan-Meier Estimate
  • Linkage Disequilibrium / genetics
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Polymorphism, Single Nucleotide / genetics*
  • Prognosis
  • Proportional Hazards Models
  • Receptors, Calcitriol / genetics*
  • Squamous Cell Carcinoma of Head and Neck


  • Receptors, Calcitriol