ORIGINAL ARTICLESPolymorphisms of vitamin D receptor gene protect against the risk of head and neck cancerLiu, Zhenshenga; Calderon, John I.a; Zhang, Zhengdonga; Sturgis, Erich M.a b; Spitz, Margaret R.a; Wei, QingyiaAuthor Information Departments of aEpidemiology bHead and Neck Surgery, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA Sponsorship: This study was supported by grants from National Institutes of Health grants ES 11740 and CA 100264 (to Q.W.), CA 86390 (to M.R.S.), CA 16672 (to MD Anderson Cancer Center) and ES 11047 and ES 07784 (Center Grants from the National Institute of Environmental Health Sciences). Correspondence and requests for reprints to Dr Qingyi Wei, Department of Epidemiology, Unit 189, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA Tel: +1 713 792 3020; fax: +1 713 563 0999; e-mail: [email protected] Received 8 September 2004 Accepted 29 November 2004 Pharmacogenetics and Genomics: March 2005 - Volume 15 - Issue 3 - p 159-165 Buy Abstract Vitamin D has potent anti-tumour properties. Calcitriol [1,25(OH)2D3], the hormonal derivative of vitamin D3, is an antiproliferative and prodifferentiation factor for several cell types, including human squamous cells of the head and neck. Several polymorphisms of the vitamin D receptor (VDR) gene have been described, including a FokI restriction fragment-length polymorphism (RFLP) in exon 2 and an adjacent TaqI RFLP in exon 9. We hypothesized that the VDR FokI and TaqI polymorphisms are associated with the risk of developing squamous cell carcinoma of the head and neck (SCCHN). We conducted a hospital-based, case–control study of 719 SCCHN cases and 821 cancer-free controls (all non-Hispanic Whites) to assess the association between VDR polymorphisms and SCCHN risk. The cases and controls were frequency-matched on age, sex and ethnicity. Polymorphisms at the TaqI and FokI restriction sites were determined from genomic DNA by polymerase chain reaction-RFLP methods. Both homozygous variant genotypes (ff and tt) were associated with a decreased risk of SCCHN [odds ratio (OR)=0.72, 95% confidence interval (CI)=0.53–0.98 and OR=0.64, 95% CI=0.47–0.87, respectively] compared to the common FF and TT genotypes. The VDR variant genotypes were associated with a decreasing risk of SCCHN in a variant allele dose-dependent manner, and the decreasing trend in OR was statistically significant, particularly for the combined genotypes (Ptrend<0.001). These data suggest that the VDR f and t alleles and their genotypes may protect against SCCHN. However, further studies are warranted to confirm these findings. © 2005 Lippincott Williams & Wilkins, Inc.