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

Abul Kalam Azad, Isabelle Bairati, Xin Qiu, Huayi Huang, Dangxiao Cheng, Geoffrey Liu, Francois Meyer, Araba Adjei, Wei Xu

Research output: Contribution to journalArticlepeer-review

15 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)2520-2527
Number of pages8
JournalInternational Journal of Cancer
Volume132
Issue number11
DOIs
StatePublished - Jun 1 2013
Externally publishedYes

Keywords

  • genetic sequence variant
  • head and neck cancer
  • overall survival
  • second primary cancer
  • serum vitamin D level

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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