Tumor Biology

, Volume 36, Issue 8, pp 6425–6431 | Cite as

Vitamin D receptor gene polymorphisms and breast cancer risk among postmenopausal Egyptian women

  • Eman Abd-Elkader Abd-Elsalam
  • Nadia A. Ismaeil
  • Hoda Sibai Abd-Alsalam
Research Article

Abstract

Many studies reported that vitamin D can protect against various types of cancers. The mechanism of vitamin D action is mediated by the vitamin D receptor (VDR). VDR may have anti-stress function because it has been identified as p53 direct target gene. This research was designed to investigate the role of VDR polymorphisms BsmI (rs 1544410), ApaI (rs 7975232), TaqI (rs 731236), and FokI (rs 10735810) in pathogenesis of breast cancer using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis. The study included 130 postmenopausal breast cancer cases aged 49 to 65 years and 100 controls aged 50 to 72 years. A significantly increased risk of breast cancer among carriers of BsmI bb genotype was observed (OR = 2.5 (1.1–5.6), P = 0.025). Also, a significantly increased risk of breast cancer was detected among women carrying ApaI aa genotype (OR = 2.2 (1.02–4.5), P = 0.04), while no significant associations were observed between breast cancer risk and genotypes and allele frequencies of FokI and TaqI polymorphisms (P > 0.05). Our study showed that VDR gene polymorphisms (BsmI and ApaI) may contribute to breast cancer risk among postmenopausal women.

Keywords

VDR Breast cancer BsmI ApaI Polymorphism 

Abbreviations

VDR

Vitamin D receptor

SNPs

Single-nucleotide polymorphisms

PCR

polymerase chain reaction

RFLP

Restriction fragment length polymorphism

ER

Estrogen receptor

PR

Progesterone receptor

Notes

Acknowledgments

Authors are deeply grateful to all volunteers and patients.

Conflict of interest

None

References

  1. 1.
    Bretherton-Watt D, Given-Wilson R, Mansi JL, Thomas V, Carter N, Colston KW. Vitamin D receptor gene polymorphisms are associated with breast cancer risk in a UK Caucasian population. Br J Cancer. 2001;85(2):171–5.CrossRefPubMedPubMedCentralGoogle Scholar
  2. 2.
    Buyru N, Tezol A, Yosunkaya-Fenerci E, Dalay N. Vitamin D receptor gene polymorphisms in breast cancer. Exp Mol Med. 2003;35:550–5.CrossRefPubMedGoogle Scholar
  3. 3.
    Chen WY, Bertone-Johnson ER, Hunter DJ, Willett WC, Hankinson SE. Associations between polymorphisms in the vitamin D receptor and breast cancer risk. Cancer Epidemiol Biomarkers Prev. 2005;14:2335–9.CrossRefPubMedGoogle Scholar
  4. 4.
    Curran JE, Vaughan T, Lea RA, Weinstein SR, Morrison NA, Griffiths LR. Association of a Vitamin D receptor polymorphism with sporadic breast cancer development. Int J Cancer. 1999;83:723–6.CrossRefPubMedGoogle Scholar
  5. 5.
    Dalessandri KM, Rei M, Wiencke JK, Farren G, Pugh TW, Manjeshwar S, et al. Vitamin D receptor polymorphisms and breast cancer risk in a high-incidence population: a pilot study. J Am Coll Surg. 2012;215(5):652–7.CrossRefPubMedGoogle Scholar
  6. 6.
    Engel LS, Orlow I, Sima CS, Satagopan JM, Mujumdar UJ, et al. Vitamin D receptor gene haplotypes and polymorphisms and risk of breast cancer: a nested case-control study. Cancer Epidemiol Biomarkers Prev. 2012;21(10):1856–67.CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Fleet JC, DeSmet M, Johnson R, Li Y. Vitamin D and cancer: a review of molecular mechanisms. Biochem J. 2012;441(1):61–76.CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    Guy M, Lowe LC, Bretherton-Watt D, Mansi JL, Peckitt C, Bliss J, et al. Vitamin D receptor gene polymorphisms and breast cancer risk. Clin Cancer Res. 2004;10:5472–81.CrossRefPubMedGoogle Scholar
  9. 9.
    Lopes N, Sousa B, Martins D, Gomes M, Vieira D, Veronese LA, et al. Alterations in Vitamin D signaling and metabolic pathways in breast cancer progression: a study of VDR, CYP27B1 and CYP24A1 expression in benign and malignant breast lesions. BMC Cancer. 2010;10:483.CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Lowe LC, Guy M, Mansi JL, Peckitt C, Bliss J, Wilson RG, et al. Plasma 25-hydroxy vitamin D concentrations, vitamin D receptor genotype and breast cancer risk in a UK Caucasian population. Eur J Cancer. 2005;41:1164–9.CrossRefPubMedGoogle Scholar
  11. 11.
    Marik R, Fackler M, Gabrielson E, Zeiger MA, Sukumar S, et al. DNA methylation-related vitamin D receptor insensitivity in breast cancer. Cancer Biol Ther. 2010;10(1):44–53.CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    McCullough ML, Stevens VL, Diver WR, Feigelson HS, Rodriguez C, Bostick RM, et al. Vitamin D pathway gene polymorphisms, calcium intake, and risk of postmenopausal breast cancer. Breast Cancer Res. 2007;9(1):R9.CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    McKay JD, McCullough ML, Ziegler RG, Kraft P, Saltzman BS, Riboli E, et al. Vitamin D receptor polymorphisms and breast cancer risk: results from the national cancer institute breast and prostate cancer cohort consortium. Cancer Epidemiol Biomarkers Prev. 2009;18:297–305.CrossRefPubMedGoogle Scholar
  14. 14.
    Maruyama R, Aoki F, Toyota M, Sasaki Y, Akashi H, Mita H, et al. Comparative genome analysis identifies the vitamin D receptor gene as a direct target of p53-mediated transcriptional activation. Cancer Res. 2006;66:4574–83.CrossRefPubMedGoogle Scholar
  15. 15.
    Mathiasen IS, Lademann U, Jäättelä M. Apoptosis induced by vitamin D compounds in breast cancer cells is inhibited by Bcl-2 but does Not involve known caspases or p53. Cancer Res. 1999;59(19):4848–56.PubMedGoogle Scholar
  16. 16.
    Mehta RG, Moriarty RM, Mehta RR, Penmasta R, Lazzaro G, Constantinou A, et al. Prevention of preneoplastic mammary lesion development by a novel vitamin D analogue, 1alpha-hydroxyvitamin D5. J Natl Cancer Inst. 1997;89:212–8.CrossRefPubMedGoogle Scholar
  17. 17.
    Mehta RG, Peng X, Alimirah F, Murillo G, Mehta R. Vitamin D and breast cancer: emerging concepts. Cancer Lett. 2012;334(1):95–100.CrossRefPubMedGoogle Scholar
  18. 18.
    Mishra DK, Wu Y, Sarkissyan M, Sarkissyan S, Chen Z, Shang X, et al. Vitamin D receptor gene polymorphisms and prognosis of breast cancer among African-American and hispanic women. PLoS One. 2013;8(3):e57967.CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    Qi X, Pramanik R, Wang J, Schultz RM, Maitra RK, Han J, et al. The p38 and JNK pathways cooperate to trans-activate vitamin D receptor via c-Jun/AP-1 and sensitize human breast cancer cells to vitamin D(3)-induced growth inhibition. J Biol Chem. 2002;277:25884–92.CrossRefPubMedGoogle Scholar
  20. 20.
    Rezende VB, Barbosa Jr F, Montenegro MF, Sandrim VC, Gerlach RF, Tanus-Santos JE. An interethnic comparison of the distribution of vitamin D receptor genotypes and haplotypes. Clin Chim Acta. 2007;384(1–2):155–9.CrossRefPubMedGoogle Scholar
  21. 21.
    Rollison DE, Cole AL, Tung KH, Slattery ML, Baumgartner KB, Byers T, et al. Vitamin D intake, vitamin D receptor polymorphisms, and breast cancer risk among women living in the southwestern U.S. Breast Cancer Res Treat. 2012;132(2):683–91.CrossRefPubMedGoogle Scholar
  22. 22.
    Shahbazi S, Alavi S, Majidzadeh-A K, Ghaffarpour M, Soleimani A, Mahdian R. BsmI but not FokI polymorphism of VDR gene is contributed in breast cancer. Med Oncol. 2013;30(1):393–8.Google Scholar
  23. 23.
    Tang C, Chen N, Wu M, Yuan H, Du Y. FokI polymorphism of vitamin D receptor gene contributes to breast cancer susceptibility: a meta-analysis. Breast Cancer Res Treat. 2009;117:391–9.CrossRefPubMedGoogle Scholar
  24. 24.
    Trabert B, Mlone KE, Daling JR, Doody DR, Bernstein L, Ursin G, et al. Vitamin D receptor polymorphisms and breast cancer risk in a large population-based case-control study of Caucasian and African-American women. Breast Cancer Res. 2007;9:R84.CrossRefPubMedPubMedCentralGoogle Scholar
  25. 25.
    Vandevyver C, Wylin T, Cassiman JJ, Raus J, Geusens P. Influence of the vitamin D receptor gene alleles on bone mineral density in postmenopausal and osteoporotic women. J Bone Miner Res. 1997;12(2):241–7.CrossRefPubMedGoogle Scholar
  26. 26.
    Welsh J. Vitamin D, metabolism in mammary gland and breast cancer. Mol Cell Endocrinol. 2011;347:55–60.CrossRefPubMedGoogle Scholar
  27. 27.
    Welsh J. Cellular and molecular effects of vitamin D on carcinogenesis. Arch Biochem Biophys. 2012;523:107–14.CrossRefPubMedGoogle Scholar
  28. 28.
    Zhang K, Song L. Association between Vitamin D receptor gene polymorphisms and breast cancer risk: a meta-analysis of 39 studies. PLoS One. 2014;9(4):e96125.CrossRefPubMedPubMedCentralGoogle Scholar
  29. 29.
    Zinser GM, Welsh JE. Accelerated mammary gland development during pregnancy and delayed post-lactational involution in vitamin D3 receptor null mice. Mol Endocrinol. 2004;18:2208–23.CrossRefPubMedGoogle Scholar
  30. 30.
    Zinser GM, Packman K, Welsh JE. Vitamin D (3) receptor ablation alters mammary gland morphogenesis. Development. 2002;129:3067–76.PubMedGoogle Scholar

Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2015

Authors and Affiliations

  • Eman Abd-Elkader Abd-Elsalam
    • 1
  • Nadia A. Ismaeil
    • 2
  • Hoda Sibai Abd-Alsalam
    • 3
  1. 1.Medical Biochemistry Department, Faculty of MedicineZagazig UniversityZagazigEgypt
  2. 2.General Surgery Department, Faculty of MedicineZagazig UniversityZagazigEgypt
  3. 3.Obstetrics and Gynecology Department, Faculty of MedicineZagazig UniversityZagazigEgypt

Personalised recommendations