Association between genetic variation within vitamin D receptor-DNA binding sites and risk of basal cell carcinoma

Yuan Lin, Harvind S. Chahal, Wenting Wu, Hyunje G. Cho, Katherine J. Ransohoff, Hongji Dai, Jean Y. Tang, Kavita Y. Sarin, Jiali Han

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

An increasing number of studies have reported a protective association between vitamin D and cancer risk. The vitamin D endocrine system regulates transcriptional programs involved in inflammation, cell growth and differentiation through the binding of vitamin D receptor (VDR) to specific VDR elements. However, limited attention has been given to the role of variation within VDR binding sites in the development of basal cell carcinoma (BCC). Across 2,776 previously identified VDR binding sites, we identified 2,540 independent single-nucleotide polymorphisms (SNPs) and examined their associations with BCC risk in a genome-wide association meta-analysis totaling 17,187 BCC cases and 287,054 controls from two data sets. After multiple testing corrections, we identified two SNPs at new loci (rs16917546 at 10q21.1: odds ratio (OR) = 1.06, p = 3.16 × 10−7 and rs79824801 at 12q13.3: OR = 1.10, p = 1.88 × 10−5) for the first time as independently related to BCC risk in meta-analysis; and both SNPs were nominally significant in two data sets. In addition, the SNP rs3769823 within VDR binding site at a previously reported BCC susceptibility locus (2q33.1, rs13014235) also exhibited a significant association (OR = 1.12, p = 3.99 × 10−18). A mutually adjusted model suggested that rs3769823 explained the signal in this region. Our findings support the hypothesis that inherited common variation in VDR binding sites affects the development of BCC.

Original languageEnglish (US)
Pages (from-to)2085-2091
Number of pages7
JournalInternational Journal of Cancer
Volume140
Issue number9
DOIs
StatePublished - May 1 2017

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Calcitriol Receptors
Basal Cell Carcinoma
Binding Sites
Single Nucleotide Polymorphism
DNA
Odds Ratio
Vitamin D
Meta-Analysis
Endocrine System
Genome-Wide Association Study
Cell Differentiation
Inflammation
Growth
Neoplasms

Keywords

  • basal cell carcinoma
  • genetic susceptibility
  • single nucleotide polymorphism
  • vitamin D receptor-DNA binding site

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Association between genetic variation within vitamin D receptor-DNA binding sites and risk of basal cell carcinoma. / Lin, Yuan; Chahal, Harvind S.; Wu, Wenting; Cho, Hyunje G.; Ransohoff, Katherine J.; Dai, Hongji; Tang, Jean Y.; Sarin, Kavita Y.; Han, Jiali.

In: International Journal of Cancer, Vol. 140, No. 9, 01.05.2017, p. 2085-2091.

Research output: Contribution to journalArticle

Lin, Yuan ; Chahal, Harvind S. ; Wu, Wenting ; Cho, Hyunje G. ; Ransohoff, Katherine J. ; Dai, Hongji ; Tang, Jean Y. ; Sarin, Kavita Y. ; Han, Jiali. / Association between genetic variation within vitamin D receptor-DNA binding sites and risk of basal cell carcinoma. In: International Journal of Cancer. 2017 ; Vol. 140, No. 9. pp. 2085-2091.
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abstract = "An increasing number of studies have reported a protective association between vitamin D and cancer risk. The vitamin D endocrine system regulates transcriptional programs involved in inflammation, cell growth and differentiation through the binding of vitamin D receptor (VDR) to specific VDR elements. However, limited attention has been given to the role of variation within VDR binding sites in the development of basal cell carcinoma (BCC). Across 2,776 previously identified VDR binding sites, we identified 2,540 independent single-nucleotide polymorphisms (SNPs) and examined their associations with BCC risk in a genome-wide association meta-analysis totaling 17,187 BCC cases and 287,054 controls from two data sets. After multiple testing corrections, we identified two SNPs at new loci (rs16917546 at 10q21.1: odds ratio (OR) = 1.06, p = 3.16 × 10−7 and rs79824801 at 12q13.3: OR = 1.10, p = 1.88 × 10−5) for the first time as independently related to BCC risk in meta-analysis; and both SNPs were nominally significant in two data sets. In addition, the SNP rs3769823 within VDR binding site at a previously reported BCC susceptibility locus (2q33.1, rs13014235) also exhibited a significant association (OR = 1.12, p = 3.99 × 10−18). A mutually adjusted model suggested that rs3769823 explained the signal in this region. Our findings support the hypothesis that inherited common variation in VDR binding sites affects the development of BCC.",
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