Cancer Causes & Control

, Volume 11, Issue 1, pp 25–30 | Cite as

Vitamin D receptor genotype and breast cancer in Latinas (United States)

  • Sue Ann Ingles
  • Diana G. Garcia
  • Wei Wang
  • Alexandra Nieters
  • Brian E. Henderson
  • Laurence N. Kolonel
  • Robert W. Haile
  • Gerhard A. Coetzee


Objective: Polymorphism in the vitamin D receptor (VDR) gene has been associated with variation in bone mineral density and with prostate cancer risk. The purpose of this study was to determine whether polymorphism in the VDR gene may also influence breast cancer risk.

Methods: Polymorphisms in the 5′ and 3′ ends of the VDR gene were genotyped for 143 Latina women with breast cancer and 300 cohort controls.

Results: Both the BsmI and poly-A polymorphisms in the 3′ end of the VDR gene were associated with breast cancer risk, with a trend for increasing risk with increasing number of BsmI B alleles or short (S) poly-A alleles. Compared to subjects having two long poly-A alleles (genotype LL), odds ratios (and 95% confidence intervals) were 1.5 (1.0–2.3) and 3.2 (1.5–6.9) for subjects having genotypes SL and SS, respectively. Compared to BsmI genotype bb, odds ratios (and 95% confidence intervals) were 1.6 (1.1–2.5) and 2.2 (1.0–4.7) for genotypes Bb and BB respectively. The start codon polymorphism, FokI, was not associated with breast cancer risk.

Conclusion: These results suggest that polymorphic variation in or near the 3′ end of the VDR gene influences breast cancer risk in Latina women.

breast neoplasms calcitriol cohort studies polymorphism (genetics) receptors 


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  1. 1.
    Minghetti PP, Norman AW (1988) 1,25(OH)2-vitamin D3 recep-tors: gene regulation and genetic circuitry. FASEB J 2: 3043–3053.PubMedGoogle Scholar
  2. 2.
    Darwish H, DeLuca HF (1993) Vitamin D-regulated gene expres-sion. Crit Rev Eukaryot Gene Expr 3: 89–116.PubMedGoogle Scholar
  3. 3.
    Hannah SS, Norman AW (1994) 1a,25(OH)2 vitamin D-regulated expression of the eukaryotic genome. Nutr Rev 52: 376–382.PubMedGoogle Scholar
  4. 4.
    Saijo T, Ito M, Takeda E, et al. (1991) A unique mutation in the vitamin D receptor gene in three Japanese patients with vitamin D-dependent rickets type II: Utility of single-strand conformation polymorphism analysis for heterozygous carrier detection. Am JHum Genet 49: 668–673.PubMedGoogle Scholar
  5. 5.
    Miyamoto K, Kesterson RA, Yamamoto H, et al. (1997) Struc-tural organization of the human vitamin D receptor chromosomal gene and its promoter. Mol Endocrinol 11: 1165–1179.PubMedGoogle Scholar
  6. 6.
    Dawson-Hughes B, Harris SS, Finneran S (1995) Calcium absorp-tion on high and low calcium intakes in relation to vitamin D receptor genotype. J Clin Endocrinol Metab 80: 3657–3661.PubMedGoogle Scholar
  7. 7.
    Wishart JM, Horowitz M, Need AG, et al. (1997) Relations between calcium intake, calcitriol, polymorphisms of the vitamin D receptor gene, and calcium absorption in premenopausal women. Am J Clin Nutr 65: 798–802.PubMedGoogle Scholar
  8. 8.
    Morrison NA, Qi JC, Tokita A, et al. (1994) Prediction of bone density from vitamin D receptor alleles. Nature 367: 284–287.CrossRefPubMedGoogle Scholar
  9. 9.
    Ma J, Stampfer MJ, Gann PH, et al. (1998) Vitamin D receptor polymorphisms, circulating vitamin D metabolites, and risk of prostate cancer in United States physicians. Cancer Epidemiol Biomarkers Prev 7: 385–390.PubMedGoogle Scholar
  10. 10.
    Morrison N (1998) Vitamin D receptor gene variants and osteoporosis: a contributor to the polygenic control of bone density. In: Feldman D, Glorieux FH, Pike JW, eds. Vitamin D. San Diego, CA: Academic Press, 713–732.Google Scholar
  11. 11.
    Taylor JA, Hirvonen A, Watson M, Pittman G, Mohler JL, Bell DA (1996) Association of prostate cancer with vitamin D receptor gene polymorphism. Cancer Res 56: 4108–4110.PubMedGoogle Scholar
  12. 12.
    Ingles SA, Ross RK, Yu MC, et al. (1997) Association of prostate cancer risk with genetic polymorphisms in vitamin D receptor and androgen receptor. J Natl Cancer Inst 89: 166–170.CrossRefPubMedGoogle Scholar
  13. 13.
    Ingles SA, Coetzee GA, Ross RK, et al. (1998) Association of prostate cancer with vitamin D receptor haplotypes in African-Americans. Cancer Res 58: 1620–1623.PubMedGoogle Scholar
  14. 14.
    Berger U, Wilson P, McClelland RA, et al. (1988) Immunocyto-chemical detection of 1,25–dihydroxyvitamin D receptors in normal human tissues. J Clin Endocrinol Metab 67: 607–613.PubMedGoogle Scholar
  15. 15.
    Colston KW, Berger R, Coombes RC (1989) Possible role for vitamin D in controlling breast cancer cell proliferation. Lancet 1: 188–191.PubMedGoogle Scholar
  16. 16.
    Berger U, McClelland RA, Wilson P, et al. (1991) Immunocyto-chemical determination of estrogen receptor, progesterone recep-tor, and 1,25–dihydroxyvitamin D3 receptor in breast cancer and relationship to prognosis. Cancer Res 51: 239–244.PubMedGoogle Scholar
  17. 17.
    Ingles SA, Haile RW, Henderson BE, et al. (1997) Strength of linkage disequilibrium between two vitamin D receptor markers in five ethnic groups: implications for association studies. Cancer Epidemiol Biomarkers Prev 6: 93–98.PubMedGoogle Scholar
  18. 18.
    Reichardt JKV, Makridakis N, Henderson BE, Yu MC, Pike MC, Ross RK (1995) Genetic variability of the human SRD5A2 gene: implications for prostate cancer risk. Cancer Res 55: 3973–3975.PubMedGoogle Scholar
  19. 19.
    Monroe KR, Yu MC, Kolonel LN, et al. (1995) Evidence of an X-linked or recessive genetic component to prostate cancer risk. Nat Med I: 827–829.Google Scholar
  20. 20.
    Gross C, Eccleshall TR, Malloy PJ, Villa ML, Marcus R, Feldman D (1996) The presence of a polymorphism at the translation initiation site of the vitamin D receptor gene is associated with low bone mineral density in postmenopausal Mexican-American wom-en. J Bone Miner Res 11: 1850–1855.PubMedGoogle Scholar
  21. 21.
    Breslow NE, Day NE (1980) Statistical Methods in Cancer Research, vol. 1: The Analysis of Case-Control Studies. Lyon: IARC Scientific Publications.Google Scholar
  22. 22.
    Weir BS (1990) Genetic Data Analysis. Sunderland, MA: Sinauer Associates Inc.Google Scholar
  23. 23.
    McClure L, Eccleshall TR, Gross C, et al. (1997) Vitamin D receptor polymorphisms, bone mineral density, and bone metab-olism in postmenopausal Mexican-American women. J Bone Miner Res 12: 234–240.PubMedGoogle Scholar
  24. 24.
    Tokita A, Matsumoto H, Morrison NA, et al. (1996) Vitamin D receptor alleles, bone mineral density and turnover in premeno-pausal Japanese women. J Bone Miner Res 11: 1003–1009.PubMedGoogle Scholar
  25. 25.
    Eisman JA, Martin TJ, MacIntyre I, Moseley JM (1979) 1,25–dihydroxyvitamin-D receptor in breast cancer cells. Lancet 2: 1335–1336.PubMedGoogle Scholar
  26. 26.
    Frampton RJ, Omond SA, Eisman JA (1983) Inhibition of human cancer cell growth by 1,25–dihydroxyvitamin D3 metabolites. Cancer Res 43: 4443–4447.PubMedGoogle Scholar
  27. 27.
    Chouvet C, Vicard E, Devonecc M, Saez S (1986) 1,25–dihydroxy-vitamin D3 inhibitory effect on the growth of two human breast cancer cell lines (MCF-7, BT-20). J Steroid Biochem 24: 373–376.PubMedGoogle Scholar
  28. 28.
    Haussler CA, Marion SL, Pike JW, Haussler MR (1986) 1,25–dihydroxyvitamin D3 inhibits the clonogenic growth of trans-formed cells via its receptor. Biochem Biophys Res Commun 139: 136–143.PubMedGoogle Scholar
  29. 29.
    Frappart L, Falette N, Lefebvre MF, Bremond A, Vauzelle JL, Saez S (1989) In vitro study of e.ects of 1,25 dihydroxyvitamin D3 on the morphology of human breast cancer cell line BT.20. Differentiation 40: 63–69.PubMedGoogle Scholar
  30. 30.
    Abe J, Nakano T, Nishi Y, Matsumoto T, Ogaata E, Ikeda K (1991) A novel vitamin D3 analog, 22–oxa-1,25–dihydroxyvitamin D3, inhibits the growth of human breast cancer in vitro and in vivo without causing hypercalcemia. Endocrinology 129: 832–837.PubMedGoogle Scholar
  31. 31.
    Colston KW, Chander SK, MacKay AG, Coombes RC (1992) Effects of synthetic vitamin D analogues on breast cancer cell proliferation in vivo and in vitro. Biochem Pharmacol 44: 693–702.PubMedGoogle Scholar
  32. 32.
    Colston KW, Mackay AG, James SY, Binderup L, Chander S, Coommbes RC (1992) EB1089: a new vitamin D analogue that inhibits the growth of breast cancer cells in vivo and in vitro. Biochem Pharmacol 44: 2273–2280.PubMedGoogle Scholar
  33. 33.
    Mathiasen IS, Colston KW, Binderup L (1993) EB 1089, a novel vitamin D analogue, has strong antiproliferative and differentia-tion inducing effects on cancer cells. J Steroid Biochem Mol Biol 46: 365–371.PubMedGoogle Scholar
  34. 34.
    Oikawa T, Yoshida Y, Simamra M, et al. (1991) Antitumour effect of 22–oxa-1a-25–dihydroxyvitamin D3, a potent angiogenesis inhibitor of rat mammary tumours induced by 7,12–dimethy-benz[a]anthracene. Anticancer Drugs 2: 475–481.PubMedGoogle Scholar
  35. 35.
    Abe-Hashimoto J, Kikuchi T, Matsumoto T, Nishii Y, Ogata E, Ikeda K (1993) Antitumor effect of 22–oxa-calcitriol, a non-calcemic analogue of calcitriol, in athymic mice implanted with human breast carcinoma and its synergism with tamoxifen. Cancer Res 53: 2534–2537.PubMedGoogle Scholar
  36. 36.
    Anzano MA, Smith JM, Uskokovic MR, et al. (1994) 1alpha,25–dihydroxy-16–ene-23–yne-26,27–hexa¯uorocholecalciferol (Ro24–5531), a new deltanoid (Vitamin D analogue) for prevention of breast cancer in the rat. Cancer Res 54: 1653–1656.PubMedGoogle Scholar
  37. 37.
    Buras RR, Schumaker LM, Davoodi F, et al. (1994) Vitamin D receptors in breast cancer cells. Breast Cancer Res Treat 31: 191–202.PubMedGoogle Scholar
  38. 38.
    Carling T, Rastad J, AÉkerstroÉm G, Westin G (1998) Vitamin D receptor (VDR) and parathyroid hormone messenger ribonucleic acid levels correspond to polymorphic VDR alleles in human parathyroid tumors. J Clin Endocrinol Metab 83: 2255–2259.PubMedGoogle Scholar
  39. 39.
    Verbeek W, Gombart AF, Shiohara M, Campbell M, Koeffler HP (1997) Vitamin D receptor: no evidence for allele-specific mRNA stability in cells which are heterozygous for the TaqI restriction enzyme polymorphism. Biochem Biophys Res Commun 238: 77–80.PubMedGoogle Scholar
  40. 40.
    Mocharla H, Butch AW, Pappas AA, et al. (1997) Quantification of vitamin D receptor mRNA by competitive polymerase chain reaction in PBMC: lack of correspondence with common allelic variants. J Bone Miner Res 12: 726–733.PubMedGoogle Scholar
  41. 41.
    Gross C, Musiol IM, Eccleshall TR, Malloy PJ, Feldman D (1998) Vitamin D receptor gene polymorphisms: analysis of ligand binding and hormone responsiveness in cultured skin fibroblasts. Biochem Biophys Res Commun 242: 467–473.PubMedGoogle Scholar
  42. 42.
    Cooper GS, Umbach DM (1996) Are vitamin D receptor poly-morphisms associated with bone mineral density? A meta-analysis. J Bone Miner Res 11: 1841–1849.PubMedGoogle Scholar
  43. 43.
    Rozen F, Yang X-F, Huynh H, Pollak M (1997) Antiproliferative action of vitamin D-related compounds and insulin-like growth factor-binding protesin 5 accumulation. J Natl Cancer Inst 9: 652–656.Google Scholar
  44. 44.
    Colston KW, Perks CM, Xie SP, Holly JMP (1998) Growth inhibition of both MCF-7 and Hs578T human breast cancer cell lines by vitamin D analogues is associated with increased expres-sion of insulin-like growth factor binding protein-3. J Molec Endocrinol 20: 157–162.Google Scholar
  45. 45.
    Cauley JA, Lucas FL, Kuller LH, Vogt MT, Browner WS, Cummings SR (1996) Bone mineral density and risk of breast cancer in older women. The study of osteoporotic fractures. JAMA 276: 1404–1408.PubMedGoogle Scholar
  46. 46.
    Zhang Y, Kiel DP, Kreger BE, et al. (1997) Bone mass and the risk of breast cancer among postmenopausal women. N Engl J Med 336: 611–617.PubMedGoogle Scholar
  47. 47.
    Haussler MR, Whitfield GK, Haussler CA, et al. (1998) The nuclear vitamin D receptor: biological and molecular regulatory properties revealed. J Bone Miner Res 13: 325–349.PubMedGoogle Scholar

Copyright information

© Kluwer Academic Publishers 2000

Authors and Affiliations

  • Sue Ann Ingles
    • 1
  • Diana G. Garcia
    • 1
  • Wei Wang
    • 1
  • Alexandra Nieters
    • 1
  • Brian E. Henderson
    • 1
  • Laurence N. Kolonel
    • 2
  • Robert W. Haile
    • 1
  • Gerhard A. Coetzee
    • 3
  1. 1.Department of Preventive MedicineUniversity of Southern California/Norris Comprehensive Cancer CenterLos Angeles
  2. 2.Cancer Research CenterUniversity of HawaiiHonolulu
  3. 3.Department of UrologyUniversity of Southern California/Norris Comprehensive Cancer CenterLos Angeles

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