Genetic sequence variants in vitamin D metabolism pathway genes, serum vitamin D level and outcome in head and neck cancer patients

Int J Cancer. 2013 Jun 1;132(11):2520-7. doi: 10.1002/ijc.27946. Epub 2012 Dec 14.


Although some studies have reported associations between serum vitamin D level and prognosis in several cancers, others have found associations between genetic sequence variants (GSVs) in the vitamin D metabolism pathway genes and outcomes in various cancers including head and neck cancer (HNC). We comprehensively evaluated the association and interaction of GSVs in vitamin D metabolism pathway genes and their regulatory effects on circulatory serum vitamin D level in HNC outcome. We systemically evaluated the association of 89 tagging and candidate-based GSVs in six major vitamin D metabolism pathway genes (VDR, GC, CYP24A1, CYP27A1, CYP27B1 and CYP2R1) and the circulating serum vitamin D level with overall survival (OS) and second primary cancer (SPC) in 522 Stages I-II radiation-treated patients with HNC. For OS: median follow-up time was 8 years; for SPC, 4.4 years. The most common subsite was the larynx (84%). Three hundred and twelve patients were alive at the end of follow-up for OS. SPCs were diagnosed in 108 patients and were primarily of lung (46%). Serum vitamin D levels were significantly lower in patients carrying the minor alleles of GC:rs4588 and CYP2R1:rs10500804. CYP24A1:rs2296241 was significantly associated with OS and CYP2R1:rs1993116 was with SPC. These two GSVs remained significantly associated after adjusting for serum vitamin D level and important clinical factors. GSVs in the vitamin D metabolism pathway genes were associated with disease outcomes in HNC patients; however, these GSVs are different from those affecting serum vitamin D levels.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / blood
  • Biomarkers, Tumor / genetics*
  • Cytochrome P-450 Enzyme System / genetics*
  • DNA, Neoplasm / genetics
  • Female
  • Follow-Up Studies
  • Genetic Predisposition to Disease
  • Genotype
  • Head and Neck Neoplasms / blood
  • Head and Neck Neoplasms / genetics*
  • Head and Neck Neoplasms / mortality
  • Head and Neck Neoplasms / radiotherapy
  • Humans
  • Male
  • Microsatellite Repeats
  • Middle Aged
  • Neoplasm Staging
  • Neoplasms, Second Primary / blood
  • Neoplasms, Second Primary / genetics*
  • Neoplasms, Second Primary / mortality
  • Neoplasms, Second Primary / radiotherapy
  • Polymerase Chain Reaction
  • Polymorphism, Single Nucleotide / genetics*
  • Prognosis
  • Receptors, Calcitriol / genetics
  • Risk Factors
  • Survival Rate
  • Vitamin D / blood*


  • Biomarkers, Tumor
  • DNA, Neoplasm
  • Receptors, Calcitriol
  • Vitamin D
  • Cytochrome P-450 Enzyme System