Abstract
The steroid hormone 1,25 dihydroxyvitamin D3is thought to protect against breast cancer. Its actions are mediated via the vitamin D receptor (VDR) and a number of polymorphisms in the VDR gene have been identified, some of which may alter susceptibility to breast cancer. This study has investigated whether specific VDR gene polymorphisms are associated with breast cancer risk in a UK Caucasian population. Female breast cancer patients (n=313) and control women with a negative screening mammogram (n=410) were recruited and their VDR polymorphisms were determined. The 30 VDR polymorphism BsmI was significantly associated with breast cancer risk; odds ratio bb vs. BB genotype =1.79 (95% CI, 1.12–C2.86; P=0.0221). In addition, over 70% of seven commonly used breast cancer cell lines were found to have the at-risk genotype bb. The 50 FokI gene variant was not associated with breast cancer risk. Further investigations into how these different genotypes may affect the functional mechanisms of the VDR will provide a better strategy for identifying women at risk of breast cancer and for developing improved treatments.
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Arai H, Miyamoto K, Taketani Y, Yamamoto H, Iemori Y, Morita K, Tonai T, Nishisho T, Mori S, Takeda EA (1997) A vitamin D receptor gene polymorphism in the translation initiation codon: effect on protein activity and relation to bone mineral density in Japanesewomen. J Bone Miner Res 12:915–C921
Bretherton-Watt D, Given-Wilson R, Mansi JL, Thomas V, Carter N, Coston KE (2001) Vitamin D receptor gene polymorphisms are associated with breast cancer risk in a UK population. Br J Cancer 85:171–C175
Chouvet C, Vicard E, Devonec M, Saez S (1986) 1,25-Dihydroxyvitamin D3inhibitory effect on the growth of two human breast cancer cell lines (MCF-7, BT-20). J Steroid Biochem 24:373–C376
Coles C, Condie A, Chetty U, Steel CM, Evans HJ, Prosser J (1992) p53 mutations in breast cancer. Cancer Res 52:5291–C5298
Collaborative Group on Hormonal Factors in Breast Cancer (1996) Breast cancer and hormonal contraceptives: collaborative reanalysis of individual data on 53 297 women with breast cancer and 100 239 women without breast cancer from 54 epidemiological studies.Lancet 347:1713–C1727
Colston KW, Berger U, Coombes RC (1989) Possible role for vitamin D in controlling breast cancer cell proliferation. Lancet 1:188–C191
Colston KW, Mackay AG, James SY, Binderup L, Chander S, Coombes 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–C2280
Cooper GS, Umbach DM (1996) Are vitamin D receptor polymorphisms associated with bone mineral density? A meta-analysis. J Bone Miner Res 11:1841–C1849
Curran JE, Vaughan T, Weinstein SR, Morrison NA, Griffiths LR (1999) Association of a vitamin D receptor polymorphism with sporadic breast cancer development. Int J Cancer 83:723–C726
Day DA, Tuite MF (1998) Post-transcriptional gene regulatory mechanisms in eukaryotes: an overview. J Endocrinol 157:361–C371
De Jong MM, Nolte IM, te Meerman GJ, van der Graaf WTA, Oosterwijk JC, Kleibeuker JH, Schaapveld M, de Vries EGE (2002) Genes other than BRCA1 and BRCA2 involved in breast cancer susceptibility. J Med Genet 39:225–C242
Dunning AM, Healey CS, Pharoah PD, Foster NA, Lipscombe JM, Redman KL, Easton DF, Day NE, Ponder BA (1998) No association between a polymorphism in the steroid metabolism gene CYP17 and risk of breast cancer. Br J Cancer 77:2045–C2047
Dunning AM, McBride S, Gregory J, Durocher F, Foster NA, Healey CS, Smith N, Pharoah PDP, Luben RN, Easton DF, Ponder BAJ (1999) No association between androgen or vitamin D receptor gene polymorphisms and risk of breast cancer. Carcinogenesis 20:2131–C2135
Durrin LK, Haile RW, Ingles SA, Coetzee GA (1999) Vitamin D receptor 30 untranslated region polymorphisms: lack of effect on mRNA stability. Biochem Biophysica Acta 1453:311–C320
Eisman JA, Sutherland RL, McMenemy ML, Fragonas JC, Musgrove EA, Pang GY (1989) Effects of 1,25-dihydroxyvitamin D3on cell-cycle kinetics of T 47D human breast cancer cells. J Cell Physiol 138:611–C616
Faraco JH, Morrison NA, Baker A, Shine J, Frossard PM (1989) ApaI dimorphism at the human vitamin D receptor gene locus. Nucleic Acids Res 17:2150
Freedman DM, Dosemeci M, McGlynn K (2002) Sunlight and mortality from breast, ovarian, colon, prostate, and non-melanoma skin cancer: a composite death certificate-based case–Ccontrol study. Occup Environ Med 59:257–C262
Garland FC, Garland CF, Gorham ED, Young JF (1990) Geographic variation in breast cancer mortality in the United States: a hypothesis involving exposure to solar radiation. Prev Med 19:614–C622
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 women. J Bone Miner Res 11:1850–C1855
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–C473
Hansen CM, Hamberg KJ, Binderup E, Binderup L (2000) Seocalcitol (EB 1089): a vitamin D analogue of anti-cancer potential. Background, design, synthesis, pre-clinical and clinical evaluation. Curr Pharm Des 6:803–C828
Henderson BE, Feigelson HS (2000) Hormonal carcinogenesis. Carcinogenesis 21:427–C433
Hustmyer FG, DeLuca HF, Peacock M (1993) ApaI, BsmI, EcoRV and TaqI polymorphisms at the human vitamin D receptor gene locus in Caucasians, blacks and Asians. Hum Mol Genet 2:487
Ingles SA, Haile RW, Henderson B, Coetzee GA (1997a) Polymorphisms in the 30 and 50 ends of the VDR gene are associated with breast cancer risk in African-American women. In: Norman AW, Bouillon R, Thomasset M (eds) Vitamin D: chemistry, biology and clinical applications of the steroid hormone. University of California, Riverside, pp 813–C815
Ingles SA, Ross RK, Yu MC, Irvine RA, La Pera G, Haile RW, Coetzee GA (1997b) Association of prostate cancer risk with genetic polymorphisms in vitamin D receptor and androgen receptor. J Natl Cancer Inst 89:166–C170
Ingles SA, Haile RW, Henderson BE, Kolonel LN, Nakaichi G, Shi C-Y, Yu MC, Ross RK, Coetzee GA (1997c) Strength of linkage disequilibrium between two vitamin D receptor markers in five ethnic groups: implications for association studies. Cancer Epidemiol Biomarkers Prev 6:93–C98
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–C30
James SY, Mackay AG, Colston KW (1995) Vitamin D derivatives in combination with 9-cis retinoic acid promote active cell death in breast cancer cells. J Mol Endocrinol 14:391–C 394
Janowsky EC, Lester GE, Weinberg CR, Millikan RC, Schildkraut JM, Garrett PA, Hulka BS (1999) Association between low levels of 1,25-dihydroxyvitamin D and breast cancer risk. Public Health Nutr 2:283–C291
Key TJ, Verkasalo PK, Banks E (2001) Epidemiology of breast cancer. Lancet Oncol 2:133–C140
Khuder SA, Mutgi AB, Nugent S (2001) Smoking and breast cancer: a meta-analysis. Rev Environ Health 16:253–C261
Liaw D, Marsh DJ, Li J, Dahia PL, Wang SI, Zheng Z, Bose S, Call KM, Tsou HC, Peacocke M, Eng C, Parsons R (1997) Germline mutations of the PTEN gene in Cowden disease, an inherited breast and thyroid cancer syndrome. Nat Genet 16:64–C67
Ligtenberg MJ, Hogervorst FB, Willems HW, Arts PJ, Brink G, Hageman S, Bosgoed EA, Van der Looij E, Rookus MA, Devilee P, Vos EM, Wigbout G, Struycken PM, Menko FH, Rutgers EJ, Hoefsloot EH, Mariman EC, Brunner HG, Van´t Veer LJ (1999) Characteristics of small breast and/or ovarian cancer families with germline mutations in BRCA1 and BRCA2. Br J Cancer 79:1475–C1478
Lundin A-C, Soderkvist P, Eriksson B, Bergman-Jungestrom M, Wingren S and the South-East Sweden Breast Cancer Group (1999) Association of breast cancer progression with a vitamin D receptor gene polymorphism. Cancer Res 59:2332–C2334
Ma J, Stampfer MJ, Gann PH, Hough HL, Giovannucci E, Kelsey KT, Hennekens CH, Hunter DJ (1998) Vitamin D receptor polymorphisms, circulating vitamin D metabolites, and risk of prostate cancer in United States physicians. Cancer Epidemiol Biomarkers Prev 7:385–C390
Magnusson C, Baron JA, Correia N, Bergstrom R, Adami HO, Persson I (1999) Breast-cancer risk following long-term oestrogen-and oestrogen-progestin-replacement therapy. Int J Cancer 81:339–C344
Mawer EB, Walls J, Howell A, Davies M, Ratcliffe WA, Bundred NJ (1997) Serum 1,25-dihydroxyvitamin D may be related inversely to disease activity in breast cancer patients with bone metastases. J Clin Endocrinol Metab 82:118–C122
McPherson K, Steel CM, Dixon JM (2000) ABC of breast diseases. Breast cancer-epidemiology, risk factors, and genetics. BMJ 321:624–C628
Menko FH, Rutgers EJ, Hoefsloot EH, Mariman EC, Brunner HG, Van_t Veer LJ (1999) Characteristics of small breast and/or ovarian cancer families with germline mutations in BRCA1 and BRCA2. Br J Cancer 79:1475–C1478
Mocharla H, Butch AW, Pappas AA, Flick JT, Weinstein RS, De Togni P, Jilka RL, Roberson PK, Parfitt AM, Manolagas SC (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–C733
MØk Hansen C, Hamberg KJ, Binderup E, Binderup L (2000) Seocalcitol (EB1089): a vitamin D analogue of anti-cancer potential. Background, design, synthesis, pre-clinical and clinical evaluation. Curr Pharm Design 6:803–C828
Morrison NA, Yeoman R, Kelly PJ, Eisman JA (1992) Contribution of trans-acting factor alleles to normal physiological variability: vitamin D receptor gene polymorphism and circulating osteocalcin. Proc Natl Acad Sci U S A 89:6665–C6669
Prall OW, Rogan EM, Sutherland RL (1998) Oestrogen regulation of cell cycle progression in breast cancer cells. J Steroid Biochem Mol Biol 65:169–C174
Ruggiero M, Pacini S, Aterini S, Fallai C, Ruggiero C, Pacini P (1998) Vitamin D receptor gene polymorphism is associated with metastatic breast cancer. Oncology Res 10:43–C46
Smith-Warner SA, Spiegelman D, Yaun SS, van den Brandt PA, Folsom AR, Goldbohm RA, Graham S, Holmberg L, Howe GR, Marshall JR, Miller AB, Potter JD, Speizer FE, Willett WC, Wolk A, Hunter DJ (1998) Alcohol and breast cancer in women: a pooled analysis of cohort studies. JAMA 279:535–C540
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–C4110
Thompson WD (1994) Genetic epidemiology of breast cancer. Cancer 74 [1 Suppl]:279–C287
Tokita A, Matsumoto H, Morrison NA, Tawa T, Miura Y, Fukamauchi K, Mitsuhashi N, Irimoto M, Yamamori S, Miura M, Watanabe T, Kuwabara Y, Yabuta K, Eisman JA (1996) Vitamin D receptor alleles, bone mineral density and turnover in premenopausal Japanese women. J Bone Miner Res 11:1003–C1009
van Leeuwen JP.TM, Uitterlinden AG, Pols HAP (1997) How about vitamin D receptor polymorphisms. In: Norman AW, Bouillon R, Thomasset M (eds) Vitamin D: chemistry, biology and clinical applications of the steroid hormone. University of California, Riverside, pp 795–C800
Welsh JE (1995) Induction of apoptosis in breast cancer cells in response to vitamin D and antioestrogens. Biochem Cell Biol 72:537–C545
Woodson K Ratnasinge D, Bhat NK, Stewart C, Tangrea JA, Hartman TJ, Stolzenberg-Solomon R, Virtamo J, Taylor PR and Albanes D (1999) Prevalence of disease-related DNA polymorphisms among participants in a large cancer prevention trial. Eur J Cancer Prev 8:441–C447
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Guy, M., Lowe, L.C., Bretherton-Watt, D., Mansi, J.L., Colston, K.W. (2003). Approaches to Evaluating the Association of Vitamin D Receptor Gene Polymorphisms with Breast Cancer Risk. In: Reichrath, J., Tilgen, W., Friedrich, M. (eds) Vitamin D Analogs in Cancer Prevention and Therapy. Recent Results in Cancer Research, vol 164. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-55580-0_3
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DOI: https://doi.org/10.1007/978-3-642-55580-0_3
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