Vitamin D Receptor in Breast Cancer Tissues and Its Relation to Estrogen Receptor Alpha (ER-α) Gene Expression and Serum 25-hydroxyvitamin D Levels in Egyptian Breast Cancer Patients: A Case-control Study

Clin Breast Cancer. 2019 Jun;19(3):e407-e414. doi: 10.1016/j.clbc.2018.12.019. Epub 2019 Jan 6.

Abstract

Introduction: This study aimed to explore the role of vitamin D receptor (VDR) in breast cancer tissues and its relation to serum 25-hydroxyvitamin D [25(OH)D] levels and estrogen receptor alpha (ER-α) gene expression in patients with breast cancer.

Patients and methods: Cancerous and normal breast tissues from 40 women with breast cancer were analyzed for quantification of VDR levels and ER-α gene expression. The serum levels of 25(OH)D were measured in patients with breast cancer and controls by radioimmunoassay.

Results: Patients with breast cancer had serum levels of 25(OH)D significantly lower than normal control subjects. The levels of VDR and ER-α were significantly higher in breast cancer tissues than in normal breast tissues. The serum levels of 25(OH)D were indirectly and significantly correlated with the tissue levels of both VDR and ER-α gene expression. There was a significant direct correlation between the tissue levels of VDR and ER-α gene expression. The serum 25(OH) D levels, tissue VDR levels, and ER-α gene expression levels were inversely and significantly correlated with breast cancer histopathologic grade. Women with serum 25(OH)D levels ≤ 30 nmol/L, tissue levels of VDR > 5 ng/mL, and tissue levels of ER-α gene expression > 17.7 copies had significantly increased risk for breast cancer incidence.

Conclusion: Women with low serum 25(OH)D levels, high tissue levels of VDR, and ER-α gene expression had increased risk for breast cancer. VDR are upregulated in breast cancer tissues thus it may be used for target therapy especially in hormone-negative breast cancer.

Keywords: 25-Hydroxyvitamin D; Breast cancer; Case-control study; ER-alpha gene expression; Vitamin D receptor.

MeSH terms

  • Biomarkers, Tumor / metabolism*
  • Breast Neoplasms / epidemiology*
  • Breast Neoplasms / metabolism*
  • Breast Neoplasms / pathology
  • Case-Control Studies
  • Egypt / epidemiology
  • Estrogen Receptor alpha / metabolism*
  • Female
  • Follow-Up Studies
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Incidence
  • Prognosis
  • ROC Curve
  • Receptors, Calcitriol / metabolism*
  • Vitamin D / analogs & derivatives*
  • Vitamin D / blood

Substances

  • Biomarkers, Tumor
  • ESR1 protein, human
  • Estrogen Receptor alpha
  • Receptors, Calcitriol
  • VDR protein, human
  • Vitamin D
  • 25-hydroxyvitamin D