Skip to main content

Advertisement

SpringerLink
Log in

Fok1 polymorphism of vitamin D receptor gene contributes to breast cancer susceptibility: a meta-analysis

  • Epidemiology
  • Published:
Breast Cancer Research and Treatment Aims and scope Submit manuscript

Abstract

Several polymorphisms in the vitamin D receptor (VDR) gene have been reported to influence breast cancer risk. However, the published findings have been conflicting. We conducted a meta-analysis of 21 case–control studies with Fok1 (eight studies with 5,284 cases and 7,500 controls), Bsm1 (14 studies with 5,498 cases and 7,943 controls), Apa1 (four studies with 1,138 cases and 7,943 controls), Taq1 (10 studies with 4,459 cases and 5,485 controls) polymorphisms. The results showed Fok1 polymorphism was associated with an overall significantly increased risk of breast cancer (ff vs. FF: OR = 1.15, 95% CI = 1.03–1.28; the recessive model ff vs. Ff + FF: OR = 1.14, 95% CI = 1.03–1.26). In subgroup analysis, a significant association was evident between Fok1 polymorphism and breast cancer in European population (ff vs. FF: OR = 1.16, 95% CI = 1.04–1.30; the recessive model ff vs. Ff + FF: OR = 1.15, 95% CI = 1.04–1.28). There was no between-study heterogeneity in any of these analyses. No significant associations were observed between the Bsm1, Apa1 and Taq1 variants and breast cancer risk. So, the current meta-analysis shows that Fok1 may be a susceptibility biomarker for breast cancer especially in European population.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Shin MH, Holmes MD, Hankinson SE, Wu K, Colditz GA, Willett WC (2002) Intake of dairy products, calcium, and vitamin d and risk of breast cancer. J Natl Cancer Inst 94:1301–1311

    PubMed  CAS  Google Scholar 

  2. Bertone-Johnson ER, Chen WY, Holick MF, Hollis BW, Colditz GA, Willett WC, Hankinson SE (2005) Plasma 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D and risk of breast cancer. Cancer Epidemiol Biomarkers Prev 14:1991–1997. doi:10.1158/1055-9965.EPI-04-0722

    Article  PubMed  CAS  Google Scholar 

  3. Colston K, Colston MJ, Fieldsteel AH, Feldman D (1982) 1,25-dihydroxyvitamin D3 receptors in human epithelial cancer cell lines. Cancer Res 42:856–859

    PubMed  CAS  Google Scholar 

  4. Townsend K, Banwell CM, Guy M, Colston KW, Mansi JL, Stewart PM, Campbell MJ, Hewison M (2005) Autocrine metabolism of vitamin D in normal and malignant breast tissue. Clin Cancer Res 11:3579–3586. doi:10.1158/1078-0432.CCR-04-2359

    Article  PubMed  CAS  Google Scholar 

  5. John EM, Schwartz GG, Koo J, Wang W, Ingles SA (2007) Sun exposure, vitamin D receptor gene polymorphisms, and breast cancer risk in a multiethnic population. Am J Epidemiol 166:1409–1419. doi:10.1093/aje/kwm259

    Article  PubMed  Google Scholar 

  6. Fang Y, van Meurs JB, d’Alesio A, Jhamai M, Zhao H, Rivadeneira F, Hofman A, van Leeuwen JP, Jehan F, Pols HA, Uitterlinden AG (2005) Promoter and 3′-untranslated-region haplotypes in the vitamin d receptor gene predispose to osteoporotic fracture: the rotterdam study. Am J Hum Genet 77:807–823. doi:10.1086/497438

    Article  PubMed  CAS  Google Scholar 

  7. Crofts LA, Hancock MS, Morrison NA, Eisman JA (1998) Multiple promoters direct the tissue-specific expression of novel N-terminal variant human vitamin D receptor gene transcripts. Proc Natl Acad Sci USA 95:10529–10534. doi:10.1073/pnas.95.18.10529

    Article  PubMed  CAS  Google Scholar 

  8. Ruggiero M, Pacini S, Aterini S, Fallai C, Ruggiero C, Pacini P (1998) Vitamin D receptor gene polymorphism is associated with metastatic breast cancer. Oncol Res 10:43–46

    PubMed  CAS  Google Scholar 

  9. Abbas S, Nieters A, Linseisen J, Slanger T, Kropp S, Mutschelknauss EJ, Flesch-Janys D, Chang-Claude J (2008) Vitamin D receptor gene polymorphisms and haplotypes and postmenopausal breast cancer risk. Breast Cancer Res 10:R31. doi:10.1186/bcr1994

    Article  PubMed  CAS  Google Scholar 

  10. Chen WY, Bertone-Johnson ER, Hunter DJ, Willett WC, Hankinson SE (2005) Associations between polymorphisms in the vitamin D receptor and breast cancer risk. Cancer Epidemiol Biomarkers Prev 14:2335–2339. doi:10.1158/1055-9965.EPI-05-0283

    Article  PubMed  CAS  Google Scholar 

  11. Curran JE, Vaughan T, Lea RA, Weinstein SR, Morrison NA, Griffiths LR (1999) Association of A vitamin D receptor polymorphism with sporadic breast cancer development. Int J Cancer 83:723–726. doi :10.1002/(SICI)1097-0215(19991210)83:6<723::AID-IJC4>3.0.CO;2-3

  12. 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 10:5472–5481. doi:10.1158/1078-0432.CCR-04-0206

    Article  PubMed  CAS  Google Scholar 

  13. McCullough ML, Stevens VL, Diver WR, Feigelson HS, Rodriguez C, Bostick RM, Thun MJ, Calle EE (2007) Vitamin D pathway gene polymorphisms, diet, and risk of postmenopausal breast cancer: a nested case-control study. Breast Cancer Res 9:R9. doi:10.1186/bcr1642

    Article  PubMed  CAS  Google Scholar 

  14. Sinotte M, Rousseau F, Ayotte P, Dewailly E, Diorio C, Giguere Y, Berube S, Brisson J (2008) Vitamin D receptor polymorphisms (FokI, BsmI) and breast cancer risk: association replication in two case-control studies within French Canadian population. Endocr Relat Cancer 15(4):975–983

    Article  PubMed  CAS  Google Scholar 

  15. Buyru N, Tezol A, Yosunkaya-Fenerci E, Dalay N (2003) Vitamin D receptor gene polymorphisms in breast cancer. Exp Mol Med 35:550–555

    PubMed  CAS  Google Scholar 

  16. Hefler LA, Tempfer CB, Grimm C, Lebrecht A, Ulbrich E, Heinze G, Leodolter S, Schneeberger C, Mueller MW, Muendlein A, Koelbl H (2004) Estrogen-metabolizing gene polymorphisms in the assessment of breast carcinoma risk and fibroadenoma risk in Caucasian women. Cancer 101:264–269. doi:10.1002/cncr.20361

    Article  PubMed  CAS  Google Scholar 

  17. Hou MF, Tien YC, Lin GT, Chen CJ, Liu CS, Lin SY, Huang TJ (2002) Association of vitamin D receptor gene polymorphism with sporadic breast cancer in Taiwanese patients. Breast Cancer Res Treat 74:1–7. doi:10.1023/A:1016048900049

    Article  PubMed  CAS  Google Scholar 

  18. 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 11:25–30. doi:10.1023/A:1008979417618

    Article  PubMed  CAS  Google Scholar 

  19. Lowe LC, Guy M, Mansi JL, Peckitt C, Bliss J, Wilson RG, Colston KW (2005) Plasma 25-hydroxy vitamin D concentrations, vitamin D receptor genotype and breast cancer risk in a UK Caucasian population. Eur J Cancer 41:1164–1169. doi:10.1016/j.ejca.2005.01.017

    Article  PubMed  CAS  Google Scholar 

  20. 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:R84. doi:10.1186/bcr1833

    Article  PubMed  Google Scholar 

  21. Sillanpaa P, Hirvonen A, Kataja V, Eskelinen M, Kosma VM, Uusitupa M, Vainio H, Mitrunen K (2004) Vitamin D receptor gene polymorphism as an important modifier of positive family history related breast cancer risk. Pharmacogenetics 14:239–245. doi:10.1097/00008571-200404000-00003

    Article  PubMed  Google Scholar 

  22. Dunning AM, McBride S, Gregory J, Durocher F, Foster NA, Healey CS, Smith N, Pharoah PD, Luben RN, Easton DF, Ponder BA (1999) No association between androgen or vitamin D receptor gene polymorphisms and risk of breast cancer. Carcinogenesis 20:2131–2135. doi:10.1093/carcin/20.11.2131

    Article  PubMed  CAS  Google Scholar 

  23. Lundin AC, Soderkvist P, Eriksson B, Bergman-Jungestrom M, Wingren S (1999) Association of breast cancer progression with a vitamin D receptor gene polymorphism. South-East Sweden Breast Cancer Group. Cancer Res 59:2332–2334

    PubMed  CAS  Google Scholar 

  24. Little J, Bradley L, Bray MS, Clyne M, Dorman J, Ellsworth DL, Hanson J, Khoury M, Lau J, O’Brien TR, Rothman N, Stroup D, Taioli E, Thomas D, Vainio H, Wacholder S, Weinberg C (2002) Reporting, appraising, and integrating data on genotype prevalence and gene-disease associations. Am J Epidemiol 156:300–310

    PubMed  Google Scholar 

  25. Guy M, Lowe LC, Bretherton-Watt D, Mansi JL, Colston KW (2003) Approaches to evaluating the association of vitamin D receptor gene polymorphisms with breast cancer risk. Recent Results Cancer Res 164:43–54

    PubMed  CAS  Google Scholar 

  26. VandeVord PJ, Wooley PH, Darga LL, Severson RK, Wu B, Nelson DA (2006) Genetic determinants of bone mass do not relate with breast cancer risk in US white and African-American women. Breast Cancer Res Treat 100:103–107. doi:10.1007/s10549-006-9228-6

    Article  PubMed  CAS  Google Scholar 

  27. Bretherton-Watt D, Given-Wilson R, Mansi JL, Thomas V, Carter N, Colston KW (2001) Vitamin D receptor gene polymorphisms are associated with breast cancer risk in a UK Caucasian population. Br J Cancer 85:171–175. doi:10.1054/bjoc.2001.1864

    Article  PubMed  CAS  Google Scholar 

  28. Lau J, Ioannidis JP, Schmid CH (1997) Quantitative synthesis in systematic reviews. Ann Intern Med 127:820–826

    PubMed  CAS  Google Scholar 

  29. Mantel N, Haenszel W (1959) Statistical aspects of the analysis of data from retrospective studies of disease. J Natl Cancer Inst 22:719–748

    PubMed  CAS  Google Scholar 

  30. DerSimonian R, Laird N (1986) Meta-analysis in clinical trials. Control Clin Trials 7:177–188. doi:10.1016/0197-2456(86)90046-2

    Article  PubMed  CAS  Google Scholar 

  31. Egger M, Davey Smith G, Schneider M, Minder C (1997) Bias in meta-analysis detected by a simple, graphical test. BMJ 315:629–634

    PubMed  CAS  Google Scholar 

  32. Colston KW, Berger U, Coombes RC (1989) Possible role for vitamin D in controlling breast cancer cell proliferation. Lancet 1:188–191. doi:10.1016/S0140-6736(89)91204-X

    Article  PubMed  CAS  Google Scholar 

  33. Fang Y, van Meurs JB, Bergink AP, Hofman A, van Duijn CM, van Leeuwen JP, Pols HA, Uitterlinden AG (2003) Cdx-2 polymorphism in the promoter region of the human vitamin D receptor gene determines susceptibility to fracture in the elderly. J Bone Miner Res 18:1632–1641. doi:10.1359/jbmr.2003.18.9.1632

    Article  PubMed  CAS  Google Scholar 

  34. Colin EM, Weel AE, Uitterlinden AG, Buurman CJ, Birkenhager JC, Pols HA, van Leeuwen JP (2000) Consequences of vitamin D receptor gene polymorphisms for growth inhibition of cultured human peripheral blood mononuclear cells by 1,25-dihydroxyvitamin D3. Clin Endocrinol (Oxf) 52:211–216. doi:10.1046/j.1365-2265.2000.00909.x

    Article  CAS  Google Scholar 

  35. Arai H, Miyamoto K, Taketani Y, Yamamoto H, Iemori Y, Morita K, Tonai T, Nishisho T, Mori S, Takeda E (1997) A vitamin D receptor gene polymorphism in the translation initiation codon: effect on protein activity and relation to bone mineral density in Japanese women. J Bone Miner Res 12:915–921. doi:10.1359/jbmr.1997.12.6.915

    Article  PubMed  CAS  Google Scholar 

  36. Newcomb PA, Kim H, Trentham-Dietz A, Farin F, Hunter D, Egan KM (2002) Vitamin D receptor polymorphism and breast cancer risk. Cancer Epidemiol Biomarkers Prev 11:1503–1504

    PubMed  CAS  Google Scholar 

  37. Morrison NA, Qi JC, Tokita A, Kelly PJ, Crofts L, Nguyen TV, Sambrook PN, Eisman JA (1994) Prediction of bone density from vitamin D receptor alleles. Nature 367:284–287. doi:10.1038/367284a0

    Article  PubMed  CAS  Google Scholar 

  38. Beaumont M, Bennett AJ, White DA (1998) Allelic differences in the 3′untranslated region of the vitamin D receptor gene affect mRNA levels in bone cells. Osteoporos Int 8:37

    Google Scholar 

  39. Kremer R, Bolivar I, Goltzman D, Hendy GN (1989) Influence of calcium and 1,25-dihydroxycholecalciferol on proliferation and proto-oncogene expression in primary cultures of bovine parathyroid cells. Endocrinology 125:935–941

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Dental Research Institute, School of Stomatology, Nanjing Medical University, 136 Hanzhong Rd., Nanjing, 210029, China

    Chunbo Tang, Ning Chen, Mingyue Wu, Hua Yuan & Yifei Du

Authors
  1. Chunbo Tang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ning Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Mingyue Wu
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Hua Yuan
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Yifei Du
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Ning Chen.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Tang, C., Chen, N., Wu, M. et al. Fok1 polymorphism of vitamin D receptor gene contributes to breast cancer susceptibility: a meta-analysis. Breast Cancer Res Treat 117, 391–399 (2009). https://doi.org/10.1007/s10549-008-0262-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10549-008-0262-4

Keywords

Search

Navigation