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Pathology & Oncology Research

, Volume 24, Issue 3, pp 601–607 | Cite as

Vitamin D Receptor Gene Polymorphism: Association with Susceptibility to Early-Onset Breast Cancer in Iranian, BRCA1/2-Mutation Carrier and non-carrier Patients

  • Ahmad Shahabi
  • Majid Alipour
  • Hamid Safiri
  • Parsa Tavakol
  • Mehdi Alizadeh
  • S. Milad Hashemi
  • Mahdieh Shahabi
  • Mohammad HalimiEmail author
Original Article

Abstract

Mounting evidences support that vitamin D insufficiency or deficiency is a risk factor of breast cancer. Vitamin D receptor (VDR) is expressed in more than 36 cell types in different organs as in cancerous cells. Numerous allelic variants of VDR gene have been identified in human populations. Association of FokI (rs2228570) and BsmI (rs1544410) single nucleotide polymorphisms (SNPs) in VDR gene with the risk of breast cancer have been investigated in several studies, however, the published data are still inconsistent. Here, we investigated BsmI and FokI polymorphisms in Iranian young (≤ 35 years old) breast cancer patient with known BRCA1/2 germline mutations. VDR gene polymorphisms were detected by restriction fragment length polymorphism (RFLP) analysis in a cohort of 203 breast cancer patients and 214 controls from Iran. There was a significant association between the bb and Bb genotypes of the BsmI and the increased risk of breast cancer (OR 1.74, CI 1.06–2.87 and OR 2.08, CI 1.31–3.29, respectively). This association was maintained in the subgroup of BRCA1/2 mutation non carriers (OR 1.90, CI 1.15–3.20 and OR 1.75, CI 1.07–2.87 for bb and Bb genotypes respectively) and in the subgroup of BRCA1/2 mutation non-carriers with a family history of breast and/or ovarian cancer (OR 1.81, CI 1.08–3.05 and OR 1.65, CI 1.00–2.70 for bb and Bb genotypes respectively). None of the FokI homozygous or heterozygous genotypes were associated with the risk of breast cancer. In summary, the BsmI polymorphism of VDR gene may be associated with the risk of breast cancer in Iranian women.

Keywords

Breast cancer Vitamin D receptor Polymorphism 

Notes

Acknowledgements

This work was supported by Babol Branch, Islamic Azad University.

Compliance with Ethical Standards

Funding

This work was funded through a grant provided by Babol Branch, Islamic Azad University.

Conflict of Interest

The authors declare that they have no conflict of interest.

References

  1. 1.
    Jazayeri SB, Saadat S, Ramezani R, Kaviani A (2015) Incidence of primary breast cancer in Iran: ten-year national cancer registry data report. Cancer Epidemiol 39(4):519–527CrossRefPubMedGoogle Scholar
  2. 2.
    Fackenthal JD, Olopade OI (2007) Breast cancer risk associated with BRCA1 and BRCA2 in diverse populations. Nat Rev Cancer 7(12):937–948CrossRefPubMedGoogle Scholar
  3. 3.
    Clamp A, Danson S, Clemons M (2003) Hormonal and genetic risk factors for breast cancer. Surgeon 1(1):23–31CrossRefPubMedGoogle Scholar
  4. 4.
    Martin AM, Weber BL (2000) Genetic and hormonal risk factors in breast cancer. J Natl Cancer Inst 92(14):1126–1135CrossRefPubMedGoogle Scholar
  5. 5.
    Feldman D, Krishnan AV, Swami S, Giovannucci E, Feldman BJ (2014) The role of vitamin D in reducing cancer risk and progression. Nat Rev Cancer 14(5):342–357CrossRefPubMedGoogle Scholar
  6. 6.
    Norman AW (2008) From vitamin D to hormone D: fundamentals of the vitamin D endocrine system essential for good health. Am J Clin Nutr 88(2):491S–499SCrossRefPubMedGoogle Scholar
  7. 7.
    Zmuda JM, Cauley JA, Ferrell RE (2000) Molecular epidemiology of vitamin D receptor gene variants. Epidemiol Rev 22(2):203–217CrossRefPubMedGoogle Scholar
  8. 8.
    Lopes N, Sousa B, Martins D, Gomes M, Vieira D, Veronese LA, Milanezi F, Paredes J, Costa JL, Schmitt F (2010) Alterations in vitamin D signalling and metabolic pathways in breast cancer progression: a study of VDR, CYP27B1 and CYP24A1 expression in benign and malignant breast lesions. BMC Cancer 10:483CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    O’Neill V, Asani FF, Jeffery TJ, Saccone DS, Bornman L (2013) Vitamin D receptor gene expression and function in a south African population: ethnicity, vitamin D and FokI. PLoS One 8(6):e67663CrossRefPubMedCentralGoogle Scholar
  10. 10.
    Wang J, He Q, Shao YG, Ji M, Bao W (2013) Associations between vitamin D receptor polymorphisms and breast cancer risk. Tumour Biol 34(6):3823–3830CrossRefPubMedGoogle Scholar
  11. 11.
    Rashid MU, Muzaffar M, Khan FA, Kabisch M, Muhammad N, Faiz S, Loya A, Hamann U (2015) Association between the BsmI polymorphism in the vitamin D receptor gene and Breast cancer risk: results from a Pakistani case-control study. PLoS One 10(10):e0141562CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    McKay JD, McCullough ML, Ziegler RG, Kraft P et al (2009) Vitamin D receptor polymorphisms and breast cancer risk: results from the National Cancer Institute breast and prostate cancer cohort consortium. Cancer Epidemiol Biomark Prev 18(1):297–305CrossRefGoogle Scholar
  13. 13.
    Shahbazi S, Alavi S, Majidzadeh AK, Ghaffarpour M, Soleimani A, Mahdian R (2013) BsmI but not FokI polymorphism of VDR gene is contributed in breast cancer. Med Oncol 30(1):393CrossRefPubMedGoogle Scholar
  14. 14.
    Dorjgochoo T, Delahanty R, Lu W, Long J, Cai Q, Zheng Y, Gu K, Gao YT, Zheng W, Shu XO (2011) Common genetic variants in the vitamin D pathway including genome-wide associated variants are not associated with breast cancer risk among Chinese women. Cancer Epidemiol Biomark Prev 20(10):2313–2316CrossRefGoogle Scholar
  15. 15.
    Trabert B, Malone KE, Daling JR, Doody DR, Bernstein L, Ursin G, Marchbanks PA, Strom BL, Humphrey MC, Ostrander EA (2007) 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 9(6):R84CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    Lu D, Jing L, Zhang S (2016) Vitamin D receptor polymorphism and breast cancer risk: a meta-analysis. Medicine (Baltimore) 95(18):e3535CrossRefGoogle Scholar
  17. 17.
    Mishra DK, Wu Y, Sarkissyan M, Sarkissyan S, Chen Z, Shang X, Ong M, Heber D, Koeffler HP, Vadgama JV (2013) Vitamin D receptor gene polymorphisms and prognosis of breast cancer among African-American and Hispanic women. PLoS One 8(3):e57967CrossRefPubMedPubMedCentralGoogle Scholar
  18. 18.
    Guy M, Lowe LC, Bretherton-Watt D, Mansi JL, Peckitt C, Bliss J, Wilson RG, Thomas V, Colston KW (2004) Vitamin D receptor gene polymorphisms and breast cancer risk. Clin Cancer Res 10(16):5472–5481CrossRefPubMedGoogle Scholar
  19. 19.
    Yao S, Zirpoli G, Bovbjerg DH, Jandorf L et al (2012) Variants in the vitamin D pathway, serum levels of vitamin D, and estrogen receptor negative breast cancer among African-American women: a case-control study. Breast Cancer Res 14(2):R58CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    Ingles SA, Garcia DG, Wang W, Nieters A, Henderson BE, Kolonel LN, Haile RW, Coetzee GA (2000) Vitamin D receptor genotype and breast cancer in Latinas (United States). Cancer Causes Control 11(1):25–30CrossRefPubMedGoogle Scholar

Copyright information

© Arányi Lajos Foundation 2017

Authors and Affiliations

  • Ahmad Shahabi
    • 1
    • 2
  • Majid Alipour
    • 1
  • Hamid Safiri
    • 3
  • Parsa Tavakol
    • 1
  • Mehdi Alizadeh
    • 4
  • S. Milad Hashemi
    • 1
  • Mahdieh Shahabi
    • 5
  • Mohammad Halimi
    • 1
    • 2
    Email author
  1. 1.Department of Biology, Babol BranchIslamic Azad UniversityBabolIran
  2. 2.Young Researchers and Elite Club, Babol BranchIslamic Azad UniversityBabolIran
  3. 3.Shahid Rajayee HospitalBabol University of Medical SciencesBabolIran
  4. 4.Department of biology, Faculty of Basic SciencesImam Hossein UniversityTehranIran
  5. 5.Belarusian state medical universityMinskBelarus

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