Tumor Biology

, Volume 34, Issue 6, pp 3823–3830 | Cite as

Associations between vitamin D receptor polymorphisms and breast cancer risk

Research Article

Abstract

Many epidemiologic studies have investigated the association between vitamin D receptor (VDR) gene polymorphisms and breast cancer risk, but the results were inconsistent. We performed a meta-analysis of 31 studies on VDR polymorphisms, including FokI, BsmI, TaqI, and ApaI, and breast cancer risk published before May 2013. For FokI, the allele of f was found to be associated with increased risk of breast cancer compared with F (OR, 1.19; 95 % CI, 1.03–1.36). Patients with ff genotype were at significantly higher risk of breast cancer compared with those with FF genotype (OR, 1.95; 95 % CI, 1.66–2.29). In subgroup analysis by race, Fok1 polymorphism was significantly associated with breast cancer risk for Caucasian population (f vs. F: OR, 1.35; 95 % CI, 1.14–1.59; ff vs. FF: OR, 2.18; 95 % CI, 1.86–2.54; ff vs. FF + Ff: OR, 1.16; 95 % CI, 1.03–1.30). For ApaI, aa genotype was associated with increased breast cancer risk in Asian population based on four studies (aa vs. Aa + AA, OR, 1.49; 95 % CI, 1.12–1.98). No significant association was found between breast cancer risk and ApaI and TaqI polymorphism in different models and populations. Our updated meta-analysis showed that Fok1 polymorphism is associated with breast cancer risk both in general population and in Caucasian population. ApaI polymorphism might be associated with breast cancer risk in Asian population. Large well-designed epidemiological studies are necessary to clarify the risk identified in the current meta-analysis.

Keywords

VDR Polymorphism Breast cancer Meta-analysis 

Notes

Acknowledgments

This research was supported by National Natural Science Foundation of China (81001172).

Conflicts of interest

None.

References

  1. 1.
    Bauer SR, Hankinson SE, Bertone-Johnson ER, Ding EL. Plasma vitamin D levels, menopause, and risk of breast cancer: dose–response meta-analysis of prospective studies. Med (Baltimore). 2013;92:123–31.CrossRefGoogle Scholar
  2. 2.
    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.PubMedCrossRefGoogle Scholar
  3. 3.
    Tang C, Chen N, Wu M, Yuan H, Du Y. Fok1 polymorphism of vitamin D receptor gene contributes to breast cancer susceptibility: a meta-analysis. Breast Cancer Res Treat. 2009;117:391–9.PubMedCrossRefGoogle Scholar
  4. 4.
    Raimondi S, Johansson H, Maisonneuve P, Gandini S. Review and meta-analysis on vitamin D receptor polymorphisms and cancer risk. Carcinogenesis. 2009;30:1170–80.PubMedCrossRefGoogle Scholar
  5. 5.
    Higgins JP, Thompson SG, Deeks JJ, Altman DG. Measuring inconsistency in meta-analyses. BMJ. 2003;327:557–60.PubMedCrossRefGoogle Scholar
  6. 6.
    Ruggiero M, Pacini S, Aterini S, Fallai C, Ruggiero C, Pacini P. Vitamin D receptor gene polymorphism is associated with metastatic breast cancer. Oncol Res. 1998;10:43–6.PubMedGoogle Scholar
  7. 7.
    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.PubMedCrossRefGoogle Scholar
  8. 8.
    Dunning AM, McBride S, Gregory J, Durocher F, Foster NA, Healey CS, et al. No association between androgen or vitamin D receptor gene polymorphisms and risk of breast cancer. Carcinogenesis. 1999;20:2131–5.PubMedCrossRefGoogle Scholar
  9. 9.
    Lundin AC, Soderkvist P, Eriksson B, Bergman-Jungestrom M, Wingren S. Association of breast cancer progression with a vitamin D receptor gene polymorphism. South-east Sweden breast cancer group. Cancer Res. 1999;59:2332–4.PubMedGoogle Scholar
  10. 10.
    Ingles SA, Garcia DG, Wang W, Nieters A, Henderson BE, Kolonel LN, et al. Vitamin D receptor genotype and breast cancer in Latinas (US). Cancer Causes Control. 2000;11:25–30.PubMedCrossRefGoogle Scholar
  11. 11.
    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;85:171–5.PubMedCrossRefGoogle Scholar
  12. 12.
    Jing C, Kunwei S, Zhenzou S, Feng J, Fumin S. Relationship of vitamin D receptor polymorphism with breast cancer. Chin J Med Genet. 2001;18:286–8.Google Scholar
  13. 13.
    Hou MF, Tien YC, Lin GT, Chen CJ, Liu CS, Lin SY, et al. Association of vitamin D receptor gene polymorphism with sporadic breast cancer in Taiwanese patients. Breast Cancer Res Treat. 2002;74:1–7.PubMedCrossRefGoogle Scholar
  14. 14.
    Buyru N, Tezol A, Yosunkaya-Fenerci E, Dalay N. Vitamin D receptor gene polymorphisms in breast cancer. Exp Mol Med. 2003;35:550–5.PubMedCrossRefGoogle Scholar
  15. 15.
    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.PubMedCrossRefGoogle Scholar
  16. 16.
    Hefler LA, Tempfer CB, Grimm C, Lebrecht A, Ulbrich E, Heinze G, et al. Estrogen-metabolizing gene polymorphisms in the assessment of breast carcinoma risk and fibroadenoma risk in Caucasian women. Cancer. 2004;101:264–9.PubMedCrossRefGoogle Scholar
  17. 17.
    Sillanpaa P, Hirvonen A, Kataja V, Eskelinen M, Kosma VM, Uusitupa M, et al. Vitamin D receptor gene polymorphism as an important modifier of positive family history related breast cancer risk. Pharmacogenetics. 2004;14:239–45.PubMedCrossRefGoogle Scholar
  18. 18.
    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.PubMedCrossRefGoogle Scholar
  19. 19.
    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.PubMedCrossRefGoogle Scholar
  20. 20.
    VandeVord PJ, Wooley PH, Darga LL, Severson RK, Wu B, Nelson DA. Genetic determinants of bone mass do not relate with breast cancer risk in us white and African–American women. Breast Cancer Res Treat. 2006;100:103–7.PubMedCrossRefGoogle Scholar
  21. 21.
    John EM, Schwartz GG, Koo J, Wang W, Ingles SA. Sun exposure, vitamin D receptor gene polymorphisms, and breast cancer risk in a multiethnic population. Am J Epidemiol. 2007;166:1409–19.PubMedCrossRefGoogle Scholar
  22. 22.
    McCullough ML, Stevens VL, Diver WR, Feigelson HS, Rodriguez C, Bostick RM, et al. Vitamin D pathway gene polymorphisms, diet, and risk of postmenopausal breast cancer: a nested case–control study. Breast Cancer Res. 2007;9:R9.PubMedCrossRefGoogle Scholar
  23. 23.
    Trabert B, Malone 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.PubMedCrossRefGoogle Scholar
  24. 24.
    Abbas S, Nieters A, Linseisen J, Slanger T, Kropp S, Mutschelknauss EJ, et al. Vitamin D receptor gene polymorphisms and haplotypes and postmenopausal breast cancer risk. Breast Cancer Res. 2008;10:R31.PubMedCrossRefGoogle Scholar
  25. 25.
    Sinotte M, Rousseau F, Ayotte P, Dewailly E, Diorio C, Giguere Y, et al. Vitamin D receptor polymorphisms (FOKI, BSMI) and breast cancer risk: association replication in two case–control studies within French–Canadian population. Endocr Relat Cancer. 2008;15:975–83.PubMedCrossRefGoogle Scholar
  26. 26.
    Chakraborty A, Mishra AK, Soni A, Regina T, Mohil R, Bhatnagar D, et al. Vitamin D receptor gene polymorphism(s) and breast cancer risk in north Indians. Cancer Detect Prev. 2009;32:386–94.PubMedCrossRefGoogle Scholar
  27. 27.
    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.PubMedCrossRefGoogle Scholar
  28. 28.
    Anderson LN, Cotterchio M, Cole DE, Knight JA. Vitamin D-related genetic variants, interactions with vitamin D exposure, and breast cancer risk among Caucasian women in Ontario. Cancer Epidemiol Biomarkers Prev. 2011;20:1708–17.PubMedCrossRefGoogle Scholar
  29. 29.
    Dequan L, Haichao Z, Tianning Z, Yong Z, Zhuangqing Y, Ting Y. Association between the genetic polymorphisms of Vitamin D receptor and sporadic breast cancer risk in Yunnan women of Han nationality. J Kunming Med Univ. 2011;32:91–4.Google Scholar
  30. 30.
    Dalessandri KM, Miike R, 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;215:652–7.PubMedCrossRefGoogle Scholar
  31. 31.
    Engel LS, Orlow I, Sima CS, Satagopan J, Mujumdar U, Roy P, et al. Vitamin D receptor gene haplotypes and polymorphisms and risk of breast cancer: a nested case–control study. Cancer Epidemiol Biomarkers Prev. 2012;21:1856–67.PubMedCrossRefGoogle Scholar
  32. 32.
    Huang Y, Lu H, Bai Y, Chen Y, Zeng Y, Pan Y. Relationship between genotypes and haplotypes of vitamin D receptor gene and breast cancer risk. J Med Res. 2012;41:89–92.Google Scholar
  33. 33.
    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 US. Breast Cancer Res Treat. 2012;132:683–91.PubMedCrossRefGoogle Scholar
  34. 34.
    Fuhrman BJ, Freedman DM, Bhatti P, Doody MM, Fu YP, Chang SC, et al. Sunlight, polymorphisms of vitamin D-related genes, and risk of breast cancer. Anticancer Res. 2013;33:543–51.PubMedGoogle Scholar
  35. 35.
    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:e57967.PubMedCrossRefGoogle Scholar
  36. 36.
    Shahbazi S, Alavi S, Majidzadeh AK, Ghaffarpour M, Soleimani A, Mahdian R. BSMI but not FOKI polymorphism of VDR gene is contributed in breast cancer. Med Oncol. 2013;30:393.PubMedCrossRefGoogle Scholar
  37. 37.
    Holick MF. Vitamin D deficiency. N Engl J Med. 2007;357:266–81.PubMedCrossRefGoogle Scholar
  38. 38.
    Evans RM. The steroid and thyroid hormone receptor superfamily. Science. 1988;240:889–95.PubMedCrossRefGoogle Scholar
  39. 39.
    Carlberg C. Current understanding of the function of the nuclear vitamin D receptor in response to its natural and synthetic ligands. Recent Results Cancer Res. 2003;164:29–42.PubMedCrossRefGoogle Scholar
  40. 40.
    Uitterlinden AG, Fang Y, Van Meurs JB, Pols HA, Van Leeuwen JP. Genetics and biology of vitamin D receptor polymorphisms. Gene. 2004;338:143–56.PubMedCrossRefGoogle Scholar
  41. 41.
    Uitterlinden AG, Fang Y, van Meurs JB, van Leeuwen H, Pols HA. Vitamin D receptor gene polymorphisms in relation to vitamin D related disease states. J Steroid Biochem Mol Biol. 2004;89–90:187–93.PubMedCrossRefGoogle Scholar
  42. 42.
    John EM, Schwartz GG, Dreon DM, Koo J. Vitamin D and breast cancer risk: The NHANES I epidemiologic follow-up study, 1971–1975 to 1992. National health and nutrition examination survey. Cancer Epidemiol Biomarkers Prev. 1999;8:399–406.PubMedGoogle Scholar
  43. 43.
    Rossi M, McLaughlin JK, Lagiou P, Bosetti C, Talamini R, Lipworth L, et al. Vitamin D intake and breast cancer risk: a case–control study in Italy. Ann Oncol. 2009;20:374–8.PubMedCrossRefGoogle Scholar
  44. 44.
    Abbas S, Linseisen J, Slanger T, Kropp S, Mutschelknauss EJ, Flesch-Janys D, et al. The gc2 allele of the vitamin D binding protein is associated with a decreased postmenopausal breast cancer risk, independent of the vitamin D status. Cancer Epidemiol Biomarkers Prev. 2008;17:1339–43.PubMedCrossRefGoogle Scholar

Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2013

Authors and Affiliations

  1. 1.Department of Breast Disease, The International Peace Maternity & Child Health HospitalShanghai Jiao Tong UniversityShanghaiChina
  2. 2.Department of Gynecology, The International Peace Maternity & Child Health HospitalShanghai Jiao Tong UniversityShanghaiChina

Personalised recommendations