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Vitamin D and Cancer Chemoprevention

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Bioactive Compounds and Cancer

Part of the book series: Nutrition and Health ((NH))

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Key Points

1. Although vitamin D is a nutrient whose functions are most closely linked to the control of calcium and bone metabolism, it is also proposed to have a variety of other biological roles, including anti-cancer effects.

2. There is considerable controversy as to what constitutes optimal vitamin D status. While most accept that serum 25OHD levels < 25 nmol/l are deficient and lead to rickets in growing children, some argue that serum 25OHD levels > 80 nmol/l are necessary to optimize bone health and prevent other chronic diseases like cancer.

3. Epidemiological studies have shown that high UVB exposure is associated with lower risk of a wide variety of cancers. From these observations, researchers have hypothesized a link between UVB exposure–vitamin D status and cancer risk.

4. One way that cancer can influence the effects of 1,25(OH)2 D is by influencing its metabolism. Several groups have shown that CYP27b1 activity, and the ability to produce 1,25(OH)2 D locally, is lost as cancer develops.

5. Very few intervention studies have been conducted in the area of vitamin D and cancer. In addition, the development of effective vitamin D interventions for cancer prevention or treatment may be limited by the changes in vitamin D metabolism and signaling that have been documented to occur during carcinogenesis.

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References

  1. Fleet, J.C. (2006) Molecular regulation of calcium metabolism. In: Weaver, C.M., and Heaney, R.P., eds. Calcium in Human Health. 163–90, Totowa, NJ: Humana Press.

    Chapter  Google Scholar 

  2. Apperly, F.L. (1941) The relation of solar radiation to cancer mortality in North American. Cancer Res 1, 191–95.

    Google Scholar 

  3. Garland, C.F., and Garland, F.C. (1980) Do sunlight and vitamin D reduce the likelihood of colon cancer? Int J Epidemiol 9(3), 227–31.

    Article  PubMed  CAS  Google Scholar 

  4. Schwartz, G.G., and Hulka, B.S. (1990) Is vitamin D deficiency a risk factor for prostate cancer? (Hypothesis). Anticancer Res 10(5A), 1307–11.

    PubMed  CAS  Google Scholar 

  5. Holick, M. (1997) Photobiology of vitamin D. In: Feldman, D., Glorieux, F., and Pike, J., eds. Vitamin D. 33–39, San Diego, CA: Academic Press.

    Google Scholar 

  6. Hanchette, C.L., and Schwartz, G.G. (1992) Geographic patterns of prostate cancer mortality. Evidence for a protective effect of ultraviolet radiation. Cancer 70(12), 2861–69.

    Article  PubMed  CAS  Google Scholar 

  7. Mohr, S.B., Garland, C.F., Gorham, E.D., Grant, W.B., and Garland, F.C. (2008) Relationship between low ultraviolet B irradiance and higher breast cancer risk in 107 countries. Breast J 14(3), 255–60.

    Article  PubMed  Google Scholar 

  8. Porojnicu, A.C., Dahlback, A., and Moan, J. (2008) Sun exposure and cancer survival in Norway: Changes in the risk of death with season of diagnosis and latitude. Adv Exp Med Biol 624, 43–54.

    Article  PubMed  Google Scholar 

  9. Boscoe, F.P., and Schymura, M.J. (2006) Solar ultraviolet-B exposure and cancer incidence and mortality in the United States, 1993–2002. BMC Cancer 6, 264.

    Article  PubMed  CAS  Google Scholar 

  10. Robsahm, T.E., Tretli, S., Dahlback, A., and Moan, J. (2004) Vitamin D3 from sunlight may improve the prognosis of breast-, colon- and prostate cancer (Norway). Cancer Causes Control 15(2), 149–58.

    Article  PubMed  Google Scholar 

  11. Webb, A.R., Kline, L., and Holick, M.F. (1988) Influence of season and latitude on the cutaneous synthesis of vitamin D3: Exposure to winter sunlight in Boston and Edmonton will not promote vitamin D3 synthesis in human skin. J Clin Endocrinol Metab 67(2), 373–78.

    Article  PubMed  CAS  Google Scholar 

  12. White, P., and Cooke, N. (2000) The multifunctional properties and characteristics of vitamin D-binding protein. Trends Endocrinol Metab 11(8), 320–27.

    Article  PubMed  CAS  Google Scholar 

  13. Trang, H.M., Cole, D.E., Rubin, L.A., Pierratos, A., Siu, S., and Vieth, R. (1998) Evidence that vitamin D3 increases serum 25-hydroxyvitamin D more efficiently than does vitamin D2. Am J Clin Nutr 68(4), 854–58.

    PubMed  CAS  Google Scholar 

  14. Holick, M.F. (2003) Vitamin D: A millenium perspective. J Cell Biochem 88(2), 296–307.

    Article  PubMed  CAS  Google Scholar 

  15. Glerup, H., Mikkelsen, K., Poulsen, L., Hass, E., Overbeck, S., Thomsen, J. et al. (2000) Commonly recommended daily intake of vitamin D is not sufficient if sunlight exposure is limited. J Intern Med 247(2), 260–68.

    Article  PubMed  CAS  Google Scholar 

  16. Vieth, R., Bischoff-Ferrari, H., Boucher, B.J., Dawson-Hughes, B., Garland, C.F., Heaney, R.P. et al. (2007) The urgent need to recommend an intake of vitamin D that is effective. Am J Clin Nutr 85(3), 649–650.

    PubMed  CAS  Google Scholar 

  17. Song, Y., Peng, X., Porta, A., Takanaga, H., Peng, J.B., Hediger, M.A. et al. (2003) Calcium transporter 1 and epithelial calcium channel messenger ribonucleic acid are differentially regulated by 1,25 dihydroxyvitamin D3 in the intestine and kidney of mice. Endocrinology 144(9), 3885–94.

    Article  PubMed  CAS  Google Scholar 

  18. Zierold, C., Mings, J.A., and DeLuca, H.F. (2003) Regulation of 25-hydroxyvitamin D3-24-hydroxylase mRNA by 1,25-dihydroxyvitamin D3 and parathyroid hormone. J Cell Biochem 88(2), 234–37.

    Article  PubMed  CAS  Google Scholar 

  19. Armbrecht, H.J., Boltz, M.A., and Hodam, T.L. (2003) PTH increases renal 25(OH)D3-1alpha-hydroxylase (CYP1alpha) mRNA but not renal 1,25(OH)2D3 production in adult rats. Am J Physiol Renal Physiol 284(5), F1032–F36.

    PubMed  CAS  Google Scholar 

  20. Haussler, M.R., Whitfield, G.K., Haussler, C.A., Hsieh, J.C., Thompson, P.D., Selznick, S.H. et al. (1998) The nuclear vitamin D receptor: Biological and molecular regulatory properties revealed. J Bone Miner Res 13(3), 325–49.

    Article  PubMed  CAS  Google Scholar 

  21. Song, Y., Kato, S., and Fleet, J.C. (2003) Vitamin D receptor (VDR) knockout mice reveal VDR-independent regulation of intestinal calcium absorption and ECaC2 and calbindin D9k mRNA. J Nutr 133(2), 374–80.

    PubMed  CAS  Google Scholar 

  22. Van Cromphaut, S.J., Dewerchin, M., Hoenderop, J.G., Stockmans, I., Van Herck, E., Kato, S. et al. (2001) Duodenal calcium absorption in vitamin D receptor-knockout mice: Functional and molecular aspects. Proc Natl Acad Sci U S A 98(23), 13324–29.

    Article  PubMed  Google Scholar 

  23. Song, Y., and Fleet, J.C. (2007) Intestinal resistance to 1,25 dihydroxyvitamin D in mice heterozygous for the vitamin D receptor knockout allele. Endocrinology 148, 1396–402.

    Article  PubMed  CAS  Google Scholar 

  24. Omdahl, J.L., Morris, H.A., and May, B.K. (2002) Hydroxylase enzymes of the vitamin D pathway: Expression, function, and regulation. Annu Rev Nutr 22, 139–66.

    Article  PubMed  CAS  Google Scholar 

  25. Fleet, J.C., Gliniak, C., Zhang, Z., Xue, Y., Smith, K.B., McCreedy, R. et al. (2008) Serum metabolite profiles and target tissue gene expression define the effect of cholecalciferol intake on calcium metabolism in rats and mice. J Nutr 138(6), 1114–20.

    PubMed  CAS  Google Scholar 

  26. Need, A.G., O’Loughlin, P.D., Morris, H.A., Coates, P.S., Horowitz, M., and Nordin, B.E. (2008) Vitamin D metabolites and calcium absorption in severe vitamin D deficiency. J Bone Miner Res.

    PubMed  Google Scholar 

  27. Pike, J.W., Zella, L.A., Meyer, M.B., Fretz, J.A., and Kim, S. (2007) Molecular actions of 1,25-dihydroxyvitamin D3 on genes involved in calcium homeostasis. J Bone Miner Res 22(Suppl 2), V16–V19.

    Article  PubMed  CAS  Google Scholar 

  28. Bouillon, R., Okamura, W.H., and Norman, A.W. (1995) Structure-function relationships in the vitamin D endocrine system. Endocrine Rev 16(2), 200–57.

    CAS  Google Scholar 

  29. Barsony, J., Pike, J.W., DeLuca, H.F., and Marx, S.J. (1990) Immunocytology with microwave-fixed fibroblasts shows 1 alpha,25-dihydroxyvitamin D3-dependent rapid and estrogen-dependent slow reorganization of vitamin D receptors. J Cell Biol 111(6 Pt 1), 2385–95.

    Article  PubMed  CAS  Google Scholar 

  30. Prufer, K., and Barsony, J. (2002) Retinoid X receptor dominates the nuclear import and export of the unliganded vitamin D receptor. Mol Endocrinol 16(8), 1738–51.

    Article  PubMed  CAS  Google Scholar 

  31. Barsony, J., Renyi, I., and McKoy, W. (1997) Subcellular distribution of normal and mutant vitamin D receptors in living cells. J Biol Chem 272, 5774–82.

    Article  PubMed  CAS  Google Scholar 

  32. Prufer, K., Racz, A., Lin, G.C., and Barsony, J. (2000) Dimerization with retinoid X receptors promotes nuclear localization and subnuclear targeting of vitamin D receptors. J Biol Chem 275(52), 41114–23.

    Article  PubMed  CAS  Google Scholar 

  33. Freedman, L.P. (1999) Increasing the complexity of coactivation in nuclear receptor signaling. Cell 97, 5–8.

    Article  PubMed  CAS  Google Scholar 

  34. Chen, H., Lin, R.J., Xie, W., Wilpitz, D., and Evans, R.M. (1999) Regulation of hormone-induced histone hyperacetylation and gene activation via acetylation of an acetylase. Cell 98(5), 675–86.

    Article  PubMed  CAS  Google Scholar 

  35. Belandia, B., Orford, R.L., Hurst, H.C., and Parker, M.G. (2002) Targeting of SWI/SNF chromatin remodelling complexes to estrogen-responsive genes. EMBO J 21(15), 4094–103.

    Article  PubMed  CAS  Google Scholar 

  36. Rachez, C., Lemon, B.D., Suldan, Z., Bromleigh, V., Gamble, M., Naar, A.M. et al. (1999) Ligand-dependent transcription activation by nuclear receptors requires the DRIP complex. Nature 398, 824–28.

    Article  PubMed  CAS  Google Scholar 

  37. Uitterlinden, A.G., Fang, Y., van Meurs, J.B., Pols, H.A., and van Leeuwen, J.P. (2004) Genetics and biology of vitamin D receptor polymorphisms. Gene 338(2), 143–56.

    Article  PubMed  CAS  Google Scholar 

  38. Rukin, N.J., and Strange, R.C. (2007) What are the frequency, distribution, and functional effects of vitamin D receptor polymorphisms as related to cancer risk? Nutr Rev 65(8 Pt 2), S96–S101.

    Article  PubMed  Google Scholar 

  39. Morrison, N.A., Qi, J.C., Tokita, A., Kelly, P.J., Crofts, L., Nguyen, T.V. et al. (1994) Prediction of bone density from vitamin D receptor alleles. Nature 367(6460), 284–87.

    Article  PubMed  CAS  Google Scholar 

  40. Fleet, J.C. (2007) Using genomics to understand intestinal biology. J Physiol Biochem 63(1), 83–96.

    Article  PubMed  CAS  Google Scholar 

  41. Jurutka, P., Remus, L., Whitfield, K., Thompson, P., Hsieh, J., Zitzer, H. et al. (2000) The polymorphic N terminus in human vitamin D receptor isoforms influences transcriptional activity by modulating interaction with transcription factor IIB. Mol Endocrinol 14, 401–20.

    Article  PubMed  CAS  Google Scholar 

  42. Colin, E.M., Weel, A.E., Uitterlinden, A.G., Buurman, C.J., Birkenhager, J.C., Pols, H.A. et al. (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(2), 211–16.

    Article  CAS  Google Scholar 

  43. Fleet, J.C. (2004) Rapid, membrane-initiated actions of 1,25 dihydroxyvitamin d: What are they and what do they mean? J Nutr 134(12), 3215–18.

    PubMed  CAS  Google Scholar 

  44. Farach-Carson, M.C., and Nemere, I. (2003) Membrane receptors for vitamin D steroid hormones: Potential new drug targets. Curr Drug Targets 4(1), 67–76.

    Article  PubMed  CAS  Google Scholar 

  45. Sitrin, M.D., Bissonnette, M., Bolt, M.J., Wali, R., Khare, S., Scaglione-Sewell, B. et al. (1999) Rapid effects of 1,25(OH)2 vitamin D3 on signal transduction systems in colonic cells. Steroids 64(1–2), 137–42.

    Article  PubMed  CAS  Google Scholar 

  46. Chen, A.P., Davis, B.H., Bissonnette, M., Scaglione-Sewell, B., and Brasitus, T.A. (1999) 1,25-dihydroxyvitamin D-3 stimulates activator protein-1-dependent CaCo-2 cell differentiation. J Biol Chem 274(50), 35505–13.

    Article  PubMed  CAS  Google Scholar 

  47. Khanal, R.C., and Nemere, I. (2008) Regulation of intestinal calcium transport. Annu Rev Nutr 28, 179–96.

    Article  PubMed  CAS  Google Scholar 

  48. Huhtakangas, J.A., Olivera, C.J., Bishop, J.E., Zanello, L.P., and Norman, A.W. (2004) The vitamin D receptor is present in caveolae-enriched plasma membranes and binds 1{alpha},25(OH)2-vitamin D3 in vivo and in vitro. Mol Endocrinol 18, 2660–71.

    Article  PubMed  CAS  Google Scholar 

  49. Holick, M.F. (2005) The influence of vitamin D on bone health across the life cycle. J Nutr 135(11), 2726S–2727S.

    PubMed  CAS  Google Scholar 

  50. Giovannucci, E., Liu, Y., Rimm, E.B., Hollis, B.W., Fuchs, C.S., Stampfer, M.J. et al. (2006) Prospective study of predictors of vitamin D status and cancer incidence and mortality in men. J Natl Cancer Inst 98(7), 451–59.

    Article  PubMed  CAS  Google Scholar 

  51. Millen, A.E., and Bodnar, L.M. (2008) Vitamin D assessment in population-based studies: A review of the issues. Am J Clin Nutr 87(4), 1102S–1105S.

    PubMed  CAS  Google Scholar 

  52. Lips, P., Chapuy, M.C., Dawson-Hughes, B., Pols, H.A., and Holick, M.F. (1999) An international comparison of serum 25-hydroxyvitamin D measurements. Osteoporos Int 9(5), 394–97.

    Article  PubMed  CAS  Google Scholar 

  53. Fearon, E.R., and Vogelstein, B. (1990) A genetic model for colorectal tumorigenesis. Cell 61(5), 759–67.

    Article  PubMed  CAS  Google Scholar 

  54. Gervaz, P., Bucher, P., and Morel, P. (2004) Two colons-two cancers: Paradigm shift and clinical implications. J Surg Oncol 88(4), 261–66.

    Article  PubMed  Google Scholar 

  55. Huncharek, M., Muscat, J., and Kupelnick, B. (2008) Dairy products, dietary calcium and vitamin D intake as risk factors for prostate cancer: A meta-analysis of 26,769 cases from 45 observational studies. Nutr Cancer 60(4), 421–41.

    Article  PubMed  Google Scholar 

  56. Park, S.Y., Murphy, S.P., Wilkens, L.R., Stram, D.O., Henderson, B.E., and Kolonel, L.N. (2007) Calcium, vitamin D, and dairy product intake and prostate cancer risk: The Multiethnic Cohort Study. Am J Epidemiol 166(11), 1259–69.

    Article  PubMed  Google Scholar 

  57. Chan, J.M., Stampfer, M.J., Ma, J., Gann, P.H., Gaziano, J.M., and Giovannucci, E.L. (2001) Dairy products, calcium, and prostate cancer risk in the Physicians’ Health Study. Am J Clin Nutr 74(4), 549–54.

    PubMed  CAS  Google Scholar 

  58. Chan, J.M., Giovannucci, E., Andersson, S.O., Yuen, J., Adami, H.O., and Wolk, A. (1998) Dairy products, calcium, phosphorous, vitamin D, and risk of prostate cancer (Sweden). Cancer Causes Control 9(6), 559–66.

    Article  PubMed  CAS  Google Scholar 

  59. Allen, N.E., Key, T.J., Appleby, P.N., Travis, R.C., Roddam, A.W., Tjonneland, A. et al. (2008) Animal foods, protein, calcium and prostate cancer risk: The European Prospective Investigation into Cancer and Nutrition. Br J Cancer 98(9), 1574–81.

    Article  PubMed  CAS  Google Scholar 

  60. Ahonen, M.H., Tenkanen, L., Teppo, L., Hakama, M., and Tuohimaa, P. (2000) Prostate cancer risk and prediagnostic serum 25-hydroxyvitamin D levels (Finland). Cancer Causes Control 11(9), 847–52.

    Article  PubMed  CAS  Google Scholar 

  61. Braun, M.M., Helzlsouer, K.J., Hollis, B.W., and Comstock, G.W. (1995) Prostate cancer and prediagnostic levels of serum vitamin D metabolites (Maryland, United States). Cancer Causes Control 6(3), 235–39.

    Article  PubMed  CAS  Google Scholar 

  62. Nomura, A.M., Stemmermann, G.N., Lee, J., Kolonel, L.N., Chen, T.C., Turner, A. et al. (1998) Serum vitamin D metabolite levels and the subsequent development of prostate cancer (Hawaii, United States). Cancer Causes Control 9(4), 425–32.

    Article  PubMed  CAS  Google Scholar 

  63. Ahn, J., Peters, U., Albanes, D., Purdue, M.P., Abnet, C.C., Chatterjee, N. et al. (2008) Serum vitamin D concentration and prostate cancer risk: A nested case-control study. J Natl Cancer Inst 100(11), 796–804.

    Article  PubMed  CAS  Google Scholar 

  64. Corder, E.H., Guess, H.A., Hulka, B.S., Friedman, G.D., Sadler, M., Vollmer, R.T. et al. (1993) Vitamin D and prostate cancer: A prediagnostic study with stored sera. Cancer Epidemiol Biomarkers Prev 2(5), 467–72.

    PubMed  CAS  Google Scholar 

  65. Li, H., Stampfer, M.J., Hollis, J.B., Mucci, L.A., Gaziano, J.M., Hunter, D. et al. (2007) A prospective study of plasma vitamin D metabolites, vitamin D receptor polymorphisms, and prostate cancer. PLoS Med 4(3), e103.

    Article  PubMed  CAS  Google Scholar 

  66. Kearney, J., Giovannucci, E., Rimm, E.B., Ascherio, A., Stampfer, M.J., Colditz, G.A. et al. (1996) Calcium, vitamin D, and dairy foods and the occurrence of colon cancer in men. Am J Epidemiol 143(9), 907–17.

    Article  PubMed  CAS  Google Scholar 

  67. Oh, K., Willett, W.C., Wu, K., Fuchs, C.S., and Giovannucci, E.L. (2007) Calcium and vitamin D intakes in relation to risk of distal colorectal adenoma in women. Am J Epidemiol 165(10), 1178–86.

    Article  PubMed  Google Scholar 

  68. Garland, C.F., Comstock, G.W., Garland, F.C., Helsing, K.J., Shaw, E.K., and Gorham, E.D. (1989) Serum 25-hydroxyvitamin D and colon cancer: Eight-year prospective study. Lancet 2(8673), 1176–78.

    Article  PubMed  CAS  Google Scholar 

  69. Tangrea, J., Helzlsouer, K., Pietinen, P., Taylor, P., Hollis, B., Virtamo, J. et al. (1997) Serum levels of vitamin D metabolites and the subsequent risk of colon and rectal cancer in Finnish men. Cancer Causes Control 8(4), 615–25.

    Article  PubMed  CAS  Google Scholar 

  70. Feskanich, D., Ma, J., Fuchs, C.S., Kirkner, G.J., Hankinson, S.E., Hollis, B.W. et al. (2004) Plasma vitamin D metabolites and risk of colorectal cancer in women. Cancer Epidemiol Biomarkers Prev 13(9), 1502–08.

    PubMed  CAS  Google Scholar 

  71. Wu, K., Feskanich, D., Fuchs, C.S., Willett, W.C., Hollis, B.W., and Giovannucci, E.L. (2007) A nested case control study of plasma 25-hydroxyvitamin D concentrations and risk of colorectal cancer. J Natl Cancer Inst 99(14), 1120–29.

    Article  PubMed  CAS  Google Scholar 

  72. Peters, U., Hayes, R.B., Chatterjee, N., Shao, W., Schoen, R.E., Pinsky, P. et al. (2004) Circulating vitamin D metabolites, polymorphism in vitamin D receptor, and colorectal adenoma risk. Cancer Epidemiol Biomarkers Prev 13(4), 546–52.

    PubMed  CAS  Google Scholar 

  73. Ng, K., Meyerhardt, J.A., Wu, K., Feskanich, D., Hollis, B.W., Giovannucci, E.L. et al. (2008) Circulating 25-hydroxyvitamin d levels and survival in patients with colorectal cancer. J Clin Oncol 26(18), 2984–91.

    Article  PubMed  CAS  Google Scholar 

  74. Berube, S., Diorio, C., Verhoek-Oftedahl, W., and Brisson, J. (2004) Vitamin D, calcium, and mammographic breast densities. Cancer Epidemiol Biomarkers Prev 13(9), 1466–72.

    PubMed  CAS  Google Scholar 

  75. Tseng, M., Byrne, C., Evers, K.A., and Daly, M.B. (2007) Dietary intake and breast density in high-risk women: A cross-sectional study. Breast Cancer Res 9(5), R72.

    Article  PubMed  CAS  Google Scholar 

  76. Brisson, J., Berube, S., Diorio, C., Sinotte, M., Pollak, M., and Masse, B. (2007) Synchronized seasonal variations of mammographic breast density and plasma 25-hydroxyvitamin d. Cancer Epidemiol Biomarkers Prev 16(5), 929–33.

    Article  PubMed  CAS  Google Scholar 

  77. Knight, J.A., Vachon, C.M., Vierkant, R.A., Vieth, R., Cerhan, J.R., and Sellers, T.A. (2006) No association between 25-hydroxyvitamin D and mammographic density. Cancer Epidemiol Biomarkers Prev 15(10), 1988–92.

    Article  PubMed  CAS  Google Scholar 

  78. Shin, M.H., Holmes, M.D., Hankinson, S.E., Wu, K., Colditz, G.A., and Willett, W.C. (2002) Intake of dairy products, calcium, and vitamin d and risk of breast cancer. J Natl Cancer Inst 94(17), 1301–11.

    Article  PubMed  CAS  Google Scholar 

  79. Lin, J., Manson, J.E., Lee, I.M., Cook, N.R., Buring, J.E., and Zhang, S.M. (2007) Intakes of calcium and vitamin D and breast cancer risk in women. Arch Intern Med 167(10), 1050–59.

    Article  PubMed  CAS  Google Scholar 

  80. Abbas, S., Linseisen, J., and Chang-Claude, J. (2007) Dietary vitamin D and calcium intake and premenopausal breast cancer risk in a German case-control study. Nutr Cancer 59(1), 54–61.

    Article  PubMed  CAS  Google Scholar 

  81. McCullough, M.L., Rodriguez, C., Diver, W.R., Feigelson, H.S., Stevens, V.L., Thun, M.J. et al. (2005) Dairy, calcium, and vitamin D intake and postmenopausal breast cancer risk in the Cancer Prevention Study II Nutrition Cohort. Cancer Epidemiol Biomarkers Prev 14(12), 2898–904.

    Article  PubMed  CAS  Google Scholar 

  82. Bertone-Johnson, E.R., Chen, W.Y., Holick, M.F., Hollis, B.W., Colditz, G.A., Willett, W.C. et al. (2005) Plasma 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D and risk of breast cancer. Cancer Epidemiol Biomarkers Prev 14(8), 1991–97.

    Article  PubMed  CAS  Google Scholar 

  83. Janowsky, E.C., Lester, G.E., Weinberg, C.R., Millikan, R.C., Schildkraut, J.M., Garrett, P.A. et al. (1999) Association between low levels of 1,25-dihydroxyvitamin D and breast cancer risk. Public Health Nutr 2(3), 283–91.

    Article  PubMed  CAS  Google Scholar 

  84. Freedman, D.M., Chang, S.C., Falk, R.T., Purdue, M.P., Huang, W.Y., McCarty, C.A. et al. (2008) Serum levels of vitamin D metabolites and breast cancer risk in the prostate, lung, colorectal, and ovarian cancer screening trial. Cancer Epidemiol Biomarkers Prev 17(4), 889–94.

    Article  PubMed  CAS  Google Scholar 

  85. Trabert, B., Malone, K.E., Daling, J.R., Doody, D.R., Bernstein, L., Ursin, G. et al. (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), R84.

    Article  PubMed  Google Scholar 

  86. Lowe, L.C., Guy, M., Mansi, J.L., Peckitt, C., Bliss, J., Wilson, R.G. et al. (2005) Plasma 25-hydroxy vitamin D concentrations, vitamin D receptor genotype and breast cancer risk in a UK Caucasian population. Eur J Cancer 41(8), 1164–69.

    Article  PubMed  CAS  Google Scholar 

  87. Guy, M., Lowe, L.C., Bretherton-Watt, D., Mansi, J.L., Peckitt, C., Bliss, J. et al. (2004) Vitamin D receptor gene polymorphisms and breast cancer risk. Clin Cancer Res 10(16), 5472–81.

    Article  PubMed  CAS  Google Scholar 

  88. Wedren, S., Magnusson, C., Humphreys, K., Melhus, H., Kindmark, A., Stiger, F. et al. (2007) Associations between androgen and Vitamin D receptor microsatellites and postmenopausal breast cancer. Cancer Epidemiol Biomarkers Prev 16(9), 1775–83.

    Article  PubMed  CAS  Google Scholar 

  89. Zehnder, D., Bland, R., Williams, M.C., McNinch, R.W., Howie, A.J., Stewart, P.M. et al. (2001) Extrarenal expression of 25-hydroxyvitamin d(3)-1 alpha-hydroxylase. J Clin Endocrinol Metab 86(2), 888–94.

    Article  PubMed  CAS  Google Scholar 

  90. Kemmis, C.M., Salvador, S.M., Smith, K.M., and Welsh, J. (2006) Human mammary epithelial cells express CYP27B1 and are growth inhibited by 25-hydroxyvitamin D-3, the major circulating form of vitamin D-3. J Nutr 136(4), 887–92.

    PubMed  CAS  Google Scholar 

  91. Hsu, J.Y., Feldman, D., McNeal, J.E., and Peehl, D.M. (2001) Reduced 1alpha-hydroxylase activity in human prostate cancer cells correlates with decreased susceptibility to 25-hydroxyvitamin D3-induced growth inhibition. Cancer Res 61(7), 2852–56.

    PubMed  CAS  Google Scholar 

  92. Chen, T.C., Wang, L., Whitlatch, L.W., Flanagan, J.N., and Holick, M.F. (2003) Prostatic 25-hydroxyvitamin D-1alpha-hydroxylase and its implication in prostate cancer. J Cell Biochem 88(2), 315–22.

    Article  PubMed  CAS  Google Scholar 

  93. Whitlatch, L.W., Young, M.V., Schwartz, G.G., Flanagan, J.N., Burnstein, K.L., Lokeshwar, B.L. et al. (2002) 25-Hydroxyvitamin D-1alpha-hydroxylase activity is diminished in human prostate cancer cells and is enhanced by gene transfer. J Steroid Biochem Mol Biol 81(2), 135–40.

    Article  PubMed  CAS  Google Scholar 

  94. Anderson, P.H., Hendrix, I., Sawyer, R.K., Zarrinkalam, R., Manavis, J., Sarvestani, G.T. et al. (2008) Co-expression of CYP27B1 enzyme with the 1.5 kb CYP27B1 promoter-luciferase transgene in the mouse. Mol Cell Endocrinol 285(1–2), 1–9.

    Article  PubMed  CAS  Google Scholar 

  95. Bareis, P., Kallay, E., Bischof, M.G., Bises, G., Hofer, H., Potzi, C. et al. (2002) Clonal Differences in Expression of 25-Hydroxyvitamin D(3)-1alpha- hydroxylase, of 25-Hydroxyvitamin D(3)-24-hydroxylase, and of the Vitamin D Receptor in Human Colon Carcinoma Cells: Effects of Epidermal Growth Factor and 1alpha,25-Dihydroxyvitamin D(3). Exp Cell Res 276(2), 320–27.

    Article  PubMed  CAS  Google Scholar 

  96. Matusiak, D., Murillo, G., Carroll, R.E., Mehta, R.G., and Benya, R.V. (2005) Expression of vitamin D receptor and 25-hydroxyvitamin D3-1{alpha}-hydroxylase in normal and malignant human colon. Cancer Epidemiol Biomarkers Prev 14(10), 2370–76.

    Article  PubMed  CAS  Google Scholar 

  97. Vieth, R., McCarten, K., and Norwich, K.H. (1990) Role of 25-hydroxyvitamin D3 dose in determining rat 1,25-dihydroxyvitamin D3 production. Am J Physiol 258(5 Pt 1), E780–E89.

    PubMed  CAS  Google Scholar 

  98. Colston, K., Colston, M.J., and Feldman, D. (1981) 1,25-dihydroxyvitamin D3 and malignant melanoma: The presence of receptors and inhibition of cell growth in culture. Endocrinology 108(3), 1083–86.

    Article  PubMed  CAS  Google Scholar 

  99. Lointier, P., Wargovich, M.J., Saez, S., Levin, B., Wildrick, D.M., and Boman, B.M. (1987) The role of vitamin D3 in the proliferation of a human colon cancer cell line in vitro. Anticancer Res 7(4B), 817–21.

    PubMed  CAS  Google Scholar 

  100. Gross, M., Kost, S.B., Ennis, B., Stumpf, W., and Kumar, R. (1986) Effect of 1,25-dihydroxyvitamin D3 on mouse mammary tumor (GR) cells: Evidence for receptors, cellular uptake, inhibition of growth and alteration in morphology at physiologic concentrations of hormone. J Bone Miner Res 1(5), 457–67.

    Article  PubMed  CAS  Google Scholar 

  101. Skowronski, R.J., Peehl, D.M., and Feldman, D. (1993) Vitamin D and prostate cancer: 1,25 dihydroxyvitamin D3 receptors and actions in human prostate cancer cell lines. Endocrinology 132(5), 1952–60.

    Article  PubMed  CAS  Google Scholar 

  102. Simboli-Campbell, M., Gagnon, A.M., Franks, D.J., and Welsh, J.E. (1994) 1,25-Dihydroxyvitamin D3 Translocates Protein Kinase Cß to Nucleus and Enhances Plasma Membrane Association of Protein Kinase C-alpha in Renal Epithelial Cells. J Biol Chem 269, 3257–64.

    PubMed  CAS  Google Scholar 

  103. Diaz, G.D., Paraskeva, C., Thomas, M.G., Binderup, L., and Hague, A. (2000) Apoptosis is induced by the active metabolite of vitamin D3 and its analogue EB1089 in colorectal adenoma and carcinoma cells: Possible implications for prevention and therapy. Cancer Res 60(8), 2304–12.

    PubMed  CAS  Google Scholar 

  104. Zhuang, S.H., and Burnstein, K.L. (1998) Antiproliferative effect of 1alpha,25-dihydroxyvitamin D3 in human prostate cancer cell line LNCaP involves reduction of cyclin-dependent kinase 2 activity and persistent G1 accumulation. Endocrinology 139(3), 1197–207.

    Article  PubMed  CAS  Google Scholar 

  105. Hill, R., Song, Y., Cardiff, R.D., and Van Dyke, T. (2005) Selective evolution of stromal mesenchyme with p53 loss in response to epithelial tumorigenesis. Cell 123(6), 1001–11.

    Article  PubMed  CAS  Google Scholar 

  106. Lou, Y.R., Laaksi, I., Syvala, H., Blauer, M., Tammela, T.L., Ylikomi , T.et al. (2004) 25-hydroxyvitamin D3 is an active hormone in human primary prostatic stromal cells. FASEB J 18(2), 332–34.

    PubMed  CAS  Google Scholar 

  107. Coussens, L.M., and Werb, Z. (2002) Inflammation and cancer. Nature 420(6917), 860–67.

    Article  PubMed  CAS  Google Scholar 

  108. Haverkamp, J., Charbonneau, B., and Ratliff, T.L. (2007) Prostate inflammation and its potential impact on prostate cancer: A current review. J Cell Biochem.

    Google Scholar 

  109. Cantorna, M.T., Zhu, Y., Froicu, M., and Wittke, A. (2004) Vitamin D status, 1,25-dihydroxyvitamin D3, and the immune system. Am J Clin Nutr 80(6 Suppl), 1717S–1720S.

    PubMed  CAS  Google Scholar 

  110. Adams, J.S., Liu, P.T., Chun, R., Modlin, R.L., and Hewison, M. (2007) Vitamin D in defense of the human immune response. Ann N Y Acad Sci 1117, 94–105.

    Article  PubMed  CAS  Google Scholar 

  111. Griffin, M.D., Dong, X., and Kumar, R. (2007) Vitamin D receptor-mediated suppression of RelB in antigen presenting cells: A paradigm for ligand-augmented negative transcriptional regulation. Arch Biochem Biophys 460(2), 218–26.

    Article  PubMed  CAS  Google Scholar 

  112. Cantorna, M.T., and Mahon, B.D. (2004) Mounting evidence for vitamin D as an environmental factor affecting autoimmune disease prevalence. Exp Biol Med (Maywood) 229(11), 1136–42.

    CAS  Google Scholar 

  113. Liu, M., Lee, M.H., Cohen, M., Bommakanti, M., and Freedman, L.P. (1996) Transcriptional activation of the Cdk inhibitor p21 by vitamin D leads to the induced differentiation of the myelomonocytic cell line U937. Genes Dev 10, 142–53.

    Article  PubMed  CAS  Google Scholar 

  114. Moffatt, K.A., Johannes, W.U., Hedlund, T.E., and Miller, G.J. (2001) Growth inhibitory effects of 1alpha, 25-dihydroxyvitamin D(3) are mediated by increased levels of p21 in the prostatic carcinoma cell line ALVA-31. Cancer Res 61(19), 7122–29.

    PubMed  CAS  Google Scholar 

  115. Rao, A., Coan, A., Welsh, J.E., Barclay, W.W., Koumenis, C., and Cramer, S.D. (2004) Vitamin D receptor and p21/WAF1 are targets of genistein and 1,25-dihydroxyvitamin D3 in human prostate cancer cells. Cancer Res 64(6), 2143–47.

    Article  PubMed  CAS  Google Scholar 

  116. Boyle, B.J., Zhao, X.Y., Cohen, P., and Feldman, D. (2001) Insulin-like growth factor binding protein-3 mediates 1 alpha,25- dihydroxyvitamin d(3) growth inhibition in the LNCaP prostate cancer cell line through p21/WAF1. J Urol 165(4), 1319–24.

    Article  PubMed  CAS  Google Scholar 

  117. Monti, S., Proietti-Pannunzi, L., Sciarra, A., Lolli, F., Falasca, P., Poggi, M. et al. (2007) The IGF axis in prostate cancer. Curr Pharm Des 13(7), 719–27.

    Article  PubMed  CAS  Google Scholar 

  118. Huynh, H., Pollak, M., and Zhang, J.C. (1998) Regulation of insulin-like growth factor (IGF) II and IGF binding protein 3 autocrine loop in human PC-3 prostate cancer cells by vitamin D metabolite 1,25(OH)2D3 and its analog EB1089. Int J Oncol 13(1), 137–43.

    PubMed  CAS  Google Scholar 

  119. Sprenger, C.C., Peterson, A., Lance, R., Ware, J.L., Drivdahl, R.H., and Plymate, S.R. (2001) Regulation of proliferation of prostate epithelial cells by 1,25- dihydroxyvitamin D3 is accompanied by an increase in insulin-like growth factor binding protein-3. J Endocrinol 170(3), 609–18.

    Article  PubMed  CAS  Google Scholar 

  120. Peng, L.H., Malloy, P.J., and Feldman, D. (2004) Identification of a functional vitamin D response element in the human insulin-like growth factor binding protein-3 promoter. Mol Endocrinol 18(5), 1109–19.

    Article  PubMed  CAS  Google Scholar 

  121. Macleod, K. (2000) Tumor suppressor genes. Curr Opin Genet Dev 10(1), 81–93.

    Article  PubMed  CAS  Google Scholar 

  122. Palmer, H.G., Gonzalez-Sancho, J.M., Espada, J., Berciano, M.T., Puig, I., Baulida, J. et al. (2001) Vitamin D(3) promotes the differentiation of colon carcinoma cells by the induction of E-cadherin and the inhibition of beta-catenin signaling. J Cell Biol 154(2), 369–87.

    Article  PubMed  CAS  Google Scholar 

  123. Shah, S., Islam, M.N., Dakshanamurthy, S., Rizvi, I., Rao, M., Herrell, R. et al. (2006) The molecular basis of vitamin D receptor and beta-catenin crossregulation. Mol Cell 21(6), 799–809.

    Article  PubMed  CAS  Google Scholar 

  124. Pendas-Franco, N., Garcia, J.M., Pena, C., Valle, N., Palmer, H.G., Heinaniemi, M. et al. (2008) DICKKOPF-4 is induced by TCF/beta-catenin and upregulated in human colon cancer, promotes tumour cell invasion and angiogenesis and is repressed by 1alpha,25-dihydroxyvitamin D(3). Oncogene.

    PubMed  Google Scholar 

  125. Aguilera, O., Pena, C., Garcia, J.M., Larriba, M.J., Ordonez-Moran, P., Navarro, D. et al. (2007) The Wnt antagonist DICKKOPF-1 gene is induced by 1alpha,25-dihydroxyvitamin D3 associated to the differentiation of human colon cancer cells. Carcinogenesis 28(9), 1877–84.

    Article  PubMed  CAS  Google Scholar 

  126. Krishnan, A.V., Shinghal, R., Raghavachari, N., Brooks, J.D., Peehl, D.M., and Feldman, D. (2004) Analysis of vitamin D-regulated gene expression in LNCaP human prostate cancer cells using cDNA microarrays. Prostate 59(3), 243–51.

    Article  PubMed  CAS  Google Scholar 

  127. Qiao, S., and Tuohimaa, P. (2004) The role of long-chain fatty-acid-CoA ligase 3 in vitamin D3 and androgen control of prostate cancer LNCaP cell growth. Biochem Biophys Res Commun 319(2), 358–68.

    Article  PubMed  CAS  Google Scholar 

  128. Peehl, D.M., Shinghal, R., Nonn, L., Seto, E., Krishnan, A.V., Brooks, J.D. et al. (2004) Molecular activity of 1,25-dihydroxyvitamin D3 in primary cultures of human prostatic epithelial cells revealed by cDNA microarray analysis. J Steroid Biochem Mol Biol 92(3), 131–41.

    Article  PubMed  CAS  Google Scholar 

  129. Guzey, M., Luo, J., and Getzenberg, R.H. (2004) Vitamin D3 modulated gene expression patterns in human primary normal and cancer prostate cells. J Cell Biochem 93(2), 271–85.

    Article  PubMed  CAS  Google Scholar 

  130. Towsend, K., Trevino, V., Falciani, F., Stewart, P.M., Hewison, M., and Campbell, M.J. (2006) Identification of VDR-responsive gene signatures in breast cancer cells. Oncology 71(1–2), 111–23.

    Article  PubMed  CAS  Google Scholar 

  131. Lee, H.J., Liu, H., Goodman, C., Ji, Y., Maehr, H., Uskokovic, M. et al. (2006) Gene expression profiling changes induced by a novel Gemini Vitamin D derivative during the progression of breast cancer. Biochem Pharmacol 72(3), 332–43.

    Article  PubMed  CAS  Google Scholar 

  132. Lyakhovich, A., Aksenov, N., Pennanen, P., Miettinen, S., Ahonen, M.H., Syvala, H. et al. (2000) Vitamin D induced up-regulation of keratinocyte growth factor (FGF-7/KGF) in MCF-7 human breast cancer cells. Biochem Biophys Res Commun 273(2), 675–80.

    Article  PubMed  CAS  Google Scholar 

  133. Swami, S., Raghavachari, N., Muller, U.R., Bao, Y.P., and Feldman, D. (2003) Vitamin D growth inhibition of breast cancer cells: Gene expression patterns assessed by cDNA microarray. Breast Cancer Res Treat 80(1), 49–62.

    Article  PubMed  CAS  Google Scholar 

  134. Palmer, H.G., Sanchez-Carbayo, M., Ordonez-Moran, P., Larriba, M.J., Cordon-Cardo, C., and Munoz, A. (2003) Genetic signatures of differentiation induced by 1alpha,25-dihydroxyvitamin D3 in human colon cancer cells. Cancer Res 63(22), 7799–806.

    PubMed  CAS  Google Scholar 

  135. Zhang, X.T., Krutchinsky, A., Fukuda, A., Chen, W., and Yamamura, S. (2005) Chalt BT et al. MED1/TRAP220 exists predominantly in a TRAP/mediator subpopulation enriched in RNA polymerase II and is required for ER-mediated transcription. Mol Cell 19(1), 89–100.

    Article  PubMed  CAS  Google Scholar 

  136. Akutsu, N., Lin, R., Bastien, Y., Bestawros, A., Enepekides, D.J., Black, M.J. et al. (2001) Regulation of gene Expression by 1alpha,25-dihydroxyvitamin D3 and Its analog EB1089 under growth-inhibitory conditions in squamous carcinoma Cells. Mol Endocrinol 15(7), 1127–39.

    Article  PubMed  CAS  Google Scholar 

  137. Lin, R., Nagai, Y., Sladek, R., Bastien, Y., Ho, J., Petrecca, K. et al. (2002) Expression profiling in squamous carcinoma cells reveals pleiotropic effects of vitamin D(3) analog EB1089 signaling on cell proliferation, differentiation, and immune system regulation. Mol Endocrinol 16(6), 1243–56.

    Article  PubMed  CAS  Google Scholar 

  138. Wang, T.T., Tavera-Mendoza, L.E., Laperriere, D., Libby, E., MacLeod, N.B., Nagai, Y. et al. (2005) Large-scale in silico and microarray-based identification of direct 1,25-dihydroxyvitamin D3 target genes. Mol Endocrinol 19(11), 2685–95.

    Article  PubMed  CAS  Google Scholar 

  139. Tashiro, K., Abe, T., Oue, N., Yasui, W., and Ryoji, M. (2004) Characterization of vitamin D-mediated induction of the CYP 24 transcription. Mol Cell Endocrinol 226(1–2), 27–32.

    Article  PubMed  CAS  Google Scholar 

  140. Moreno, J., Krishnan, A.V., and Feldman, D. (2005) Molecular mechanisms mediating the anti-proliferative effects of Vitamin D in prostate cancer. J Steroid Biochem Mol Biol 97(1–2), 31–36.

    Article  PubMed  CAS  Google Scholar 

  141. Ben Shoshan, M., Amir, S., Dang, D.T., Dang, L.H., Weisman, Y., and Mabjeesh, N.J. (2007) 1alpha,25-dihydroxyvitamin D3 (Calcitriol) inhibits hypoxia-inducible factor-1/vascular endothelial growth factor pathway in human cancer cells. Mol Cancer Ther 6(4), 1433–39.

    Article  PubMed  CAS  Google Scholar 

  142. Matusiak, D., Murillo, G., Carroll, R.E., Mehta, R.G., and Benya, R.V. (2005) Expression of vitamin D receptor and 25-hydroxyvitamin D3-1{alpha}-hydroxylase in normal and malignant human colon. Cancer Epidemiol Biomarkers Prev 14(10), 2370–76.

    Article  PubMed  CAS  Google Scholar 

  143. Escaleira, M.T., and Brentani, M.M. (1999) Vitamin D3 receptor (VDR) expression in HC-11 mammary cells: Regulation by growth-modulatory agents, differentiation, and Ha-ras transformation. Breast Cancer Res Treat 54(2), 123–33.

    Article  PubMed  CAS  Google Scholar 

  144. Solomon, C., White, J.H., and Kremer, R. (1999) Mitogen-activated protein kinase inhibits 1,25-dihydroxyvitamin D3- dependent signal transduction by phosphorylating human retinoid X receptor alpha. J Clin Invest 103(12), 1729–35.

    Article  PubMed  CAS  Google Scholar 

  145. Macoritto, M., Nguyen-Yamamoto, L., Huang, D.C., Samuel, S., Yang, X.F., Wang, T.T. et al. (2008) Phosphorylation of the human retinoid X receptor alpha at serine 260 impairs coactivator(s) recruitment and induces hormone resistance to multiple ligands. J Biol Chem 283(8), 4943–56.

    Article  PubMed  CAS  Google Scholar 

  146. Friedrich, M., Diesing, D., Cordes, T., Fischer, D., Becker, S., Chen, T.C. et al. (2006) Analysis of 25-hydroxyvitamin D3-1alpha-hydroxylase in normal and malignant breast tissue. Anticancer Res 26(4A), 2615–20.

    PubMed  CAS  Google Scholar 

  147. Albertson, D.G., Ylstra, B., Segraves, R., Collins, C., Dairkee, S.H., Kowbel, D. et al. (2000) Quantitative mapping of amplicon structure by array CGH identifies CYP24 as a candidate oncogene. Nat Genet 25(2), 144–46.

    Article  PubMed  CAS  Google Scholar 

  148. Anderson, M.G., Nakane, M., Ruan, X., Kroeger, P.E., and Wu-Wong, J.R. (2006) Expression of VDR and CYP24A1 mRNA in human tumors. Cancer Chemother Pharmacol 57(2), 234–40.

    Article  PubMed  CAS  Google Scholar 

  149. Matusiak, D., and Benya, R.V. (2007) CYP27A1 and CYP24 expression as a function of malignant transformation in the colon. J Histochem Cytochem 55(12), 1257–64.

    Article  PubMed  CAS  Google Scholar 

  150. Xue, L., Lipkin, M., Newmark, H., and Wang, J. (1999) Influence of dietary calcium and vitamin D on diet-induced epithelial cell hyperproliferation in mice. J Natl Cancer Inst 91(2), 176–81.

    Article  PubMed  CAS  Google Scholar 

  151. Lamprecht, S.A., and Lipkin, M. (2003) Chemoprevention of colon cancer by calcium, vitamin D and folate: Molecular mechanisms. Nat Rev Cancer 3(8), 601–14.

    Article  PubMed  CAS  Google Scholar 

  152. Kallay, E., Pietschmann, P., Toyokuni, S., Bajna, E., Hahn, P., Mazzucco, K. et al. (2001) Characterization of a vitamin D receptor knockout mouse as a model of colorectal hyperproliferation and DNA damage. Carcinogenesis 22(9), 1429–35.

    Article  PubMed  CAS  Google Scholar 

  153. Rowling, M.J., Gliniak, C., Welsh, J., and Fleet, J.C. (2007) High dietary vitamin D prevents hypocalcemia and osteomalacia in CYP27B1 knockout mice. J Nutr 137(12), 2608–15.

    PubMed  CAS  Google Scholar 

  154. Sitrin, M.D., Halline, A.G., Abrahams, C., and Brasitus, T.A. (1991) Dietary calcium and vitamin D modulate 1,2-dimethylhydrazine-induced colonic carcinogenesis in the rat. Cancer Res 51(20), 5608–13.

    PubMed  CAS  Google Scholar 

  155. Llor, X., Jacoby, R.F., Teng, B.B., Davidson, N.O., Sitrin, M.D., and Brasitus, T.A. (1991) K-ras mutations in 1,2-dimethylhydrazine-induced colonic tumors: Effects of supplemental dietary calcium and vitamin D deficiency. Cancer Res 51(16), 4305–09.

    PubMed  CAS  Google Scholar 

  156. Tangpricha, V., Spina, C., Yao, M., Chen, T.C., Wolfe, M.M., and Holick, M.F. (2005) Vitamin D deficiency enhances the growth of MC-26 colon cancer xenografts in Balb/c mice. J Nutr 135(10), 2350–54.

    PubMed  CAS  Google Scholar 

  157. Comer, P.F., Clark, T.D., and Glauert, H.P. (1993) Effect of dietary vitamin D3 (cholecalciferol) on colon carcinogenesis induced by 1,2-dimethylhydrazine in male Fischer 344 rats. Nutr Cancer 19(2), 113–24.

    Article  PubMed  CAS  Google Scholar 

  158. Beaty, M.M., Lee, E.Y., and Glauert, H.P. (1993) Influence of dietary calcium and vitamin D on colon epithelial cell proliferation and 1,2-dimethylhydrazine-induced colon carcinogenesis in rats fed high fat diets. J Nutr 123(1), 144–52.

    PubMed  CAS  Google Scholar 

  159. Valrance, M.E., Brunet, A.H., and Welsh, J. (2007) Vitamin D receptor-dependent inhibition of mammary tumor growth by EB1089 and ultraviolet radiation in vivo. Endocrinology 148(10), 4887–94.

    Article  PubMed  CAS  Google Scholar 

  160. Chen, T.C., Holick, M.F., Lokeshwar, B.L., Burnstein, K.L., and Schwartz, G.G. (2003) Evaluation of vitamin D analogs as therapeutic agents for prostate cancer. Recent Results Cancer Res 164, 273–88.

    Article  PubMed  CAS  Google Scholar 

  161. Oades, G.M., Senaratne, S.G., Clarke, I.A., Kirby, R.S., and Colston, K.W. (2003) Nitrogen containing bisphosphonates induce apoptosis and inhibit the mevalonate pathway, impairing Ras membrane localization in prostate cancer cells. J Urol 170(1), 246–52.

    Article  PubMed  CAS  Google Scholar 

  162. Huerta, S., Irwin, R.W., Heber, D., Go, V.L., Koeffler, H.P. Uskokovic, M.R. et al. (2002) 1alpha,25-(OH)(2)-D(3) and its synthetic analogue decrease tumor load in the Apc(min) Mouse. Cancer Res 62(3), 741–46.

    PubMed  CAS  Google Scholar 

  163. Mehta, R.G. (2004) Stage-specific inhibition of mammary carcinogenesis by 1alpha-hydroxyvitamin D5. Eur J Cancer 40(15), 2331–37.

    Article  PubMed  CAS  Google Scholar 

  164. Vegesna, V., O’Kelly, J., Said, J., Uskokovic, M., Binderup, L., and Koeffle, H.P. (2003) Ability of potent vitamin D3 analogs to inhibit growth of prostate cancer cells in vivo. Anticancer Res 23(1A), 283–89.

    PubMed  CAS  Google Scholar 

  165. Crescioli, C., Ferruzzi, P., Caporali, A., Scaltriti, M., Bettuzzi, S., Mancina, R. et al. (2004) Inhibition of prostate cell growth by BXL-628, a calcitriol analogue selected for a phase II clinical trial in patients with benign prostate hyperplasia. Eur J Endocrinol 150(4), 591–603.

    Article  PubMed  CAS  Google Scholar 

  166. Otoshi, T., Iwata, H., Kitano, M., Nishizawa, Y., Morii, H., Yano, Y. et al. (1995) Inhibition of intestinal tumor development in rat multi-organ carcinogenesis and aberrant crypt foci in rat colon carcinogenesis by 22-oxa-calcitriol, a synthetic analogue of 1 alpha, 25-dihydroxyvitamin D3. Carcinogenesis 16(9), 2091–97.

    Article  PubMed  CAS  Google Scholar 

  167. Fichera, A., Little, N., Dougherty, U., Mustafi, R., Cerda, S., Li, Y.C. et al. (2007) A vitamin D analogue inhibits colonic carcinogenesis in the AOM/DSS model. J Surg Res 142(2), 239–45.

    Article  PubMed  CAS  Google Scholar 

  168. Penna, G., Amuchastegui, S., Cossetti, C., Aquilano, F., Mariani, R., Sanvito, F. et al. (2006) Treatment of experimental autoimmune prostatitis in nonobese diabetic mice by the vitamin D receptor agonist elocalcitol. J Immunol 177(12), 8504–11.

    PubMed  CAS  Google Scholar 

  169. Schwartz, G.G. (2008) Vitamin D and Intervention Trials in Prostate Cancer: From Theory to Therapy. Ann Epidemiol.

    PubMed  Google Scholar 

  170. Beer, T.M., Munar, M., and Henner, W.D. (2001) A Phase I trial of pulse calcitriol in patients with refractory malignancies: Pulse dosing permits substantial dose escalation. Cancer 91(12), 2431–39.

    Article  PubMed  CAS  Google Scholar 

  171. Beer, T.M., Ryan, C.W., Venner, P.M., Petrylak, D.P., Chatta, G.S., Ruether, J.D. et al. (2007) Double-blinded randomized study of high-dose calcitriol plus docetaxel compared with placebo plus docetaxel in androgen-independent prostate cancer: A report from the ASCENT Investigators. J Clin Oncol 25(6), 669–74.

    Article  PubMed  CAS  Google Scholar 

  172. Brown, A.J. (2000) Mechanisms for the selective actions of vitamin D analogues. Curr Pharm Des 6(7), 701–16.

    Article  PubMed  CAS  Google Scholar 

  173. Norman, A.W., Mizwicki, M.T., and Okamura, W.H. (2003) Ligand structure-function relationships in the vitamin D endocrine system from the perspective of drug development (including cancer treatment). Recent Results Cancer Res 164, 55–82.

    Article  PubMed  CAS  Google Scholar 

  174. Vijayakumar, S., Mehta, R.R., Boerner, P.S., Packianathan, S., and Mehta, R.G. (2005) Clinical trials involving vitamin D analogs in prostate cancer. Cancer J 11(5), 362–73.

    Article  PubMed  CAS  Google Scholar 

  175. Wactawski-Wende, J., Kotchen, J.M., Anderson, G.L., Assaf, A.R., Brunner, R.L., O’Sullivan, M.J. et al. (2006) Calcium plus vitamin D supplementation and the risk of colorectal cancer. N Engl J Med 354(7), 684–96.

    Article  PubMed  CAS  Google Scholar 

  176. Ding, E.L., Mehta, S., Fawzi, W.W., and Giovannucci, E.L. (2008) Interaction of estrogen therapy with calcium and vitamin D supplementation on colorectal cancer risk: Reanalysis of Women’s Health Initiative randomized trial. Int J Cancer 122(8), 1690–94.

    Article  PubMed  CAS  Google Scholar 

  177. Lappe, J.M., Travers-Gustafson, D., Davies, K.M., Recker, R.R., and Heaney, R.P. (2007) Vitamin D and calcium supplementation reduces cancer risk: Results of a randomized trial. Am J Clin Nutr 85(6), 1586–91.

    PubMed  CAS  Google Scholar 

  178. Woo, T.C., Choo, R., Jamieson, M., Chander, S., and Vieth, R. (2005) Pilot study: Potential role of vitamin D (Cholecalciferol) in patients with PSA relapse after definitive therapy. Nutr Cancer 51(1), 32–36.

    Article  PubMed  CAS  Google Scholar 

  179. Nesby-O’Dell, S., Scanlon, K.S., Cogswell, M.E., Gillespie, C., Hollis, B.W., Looker, A.C. et al. (2002) Hypovitaminosis D prevalence and determinants among African American and white women of reproductive age: Third National Health and Nutrition Examination Survey, 1988–1994. Am J Clin Nutr 76(1), 187–92.

    PubMed  Google Scholar 

  180. Looker, A.C., Dawson-Hughes, B., Calvo, M.S., Gunter, E.W., and Sahyoun, N.R. (2002) Serum 25-hydroxyvitamin D status of adolescents and adults in two seasonal subpopulations from NHANES III. Bone 30(5), 771–77.

    Article  PubMed  CAS  Google Scholar 

  181. Holick, M.F., Biancuzzo, R.M., Chen, T.C., Klein, E.K., Young, A., Bibuld, D. et al. (2008) Vitamin D2 is as effective as vitamin D3 in maintaining circulating concentrations of 25-hydroxyvitamin D. J Clin Endocrinol Metab 93(3), 677–81.

    Article  PubMed  CAS  Google Scholar 

  182. Hathcock, J.N., Shao, A., Vieth, R., and Heaney, R. (2007) Risk assessment for vitamin D. Am J Clin Nutr 85(1), 6–18.

    PubMed  CAS  Google Scholar 

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  1. Department of Foods and Nutrition, Purdue University, West Lafayette, IN, USA

    James C. Fleet PHD

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  1. Nutritional Science Research Group, Division of Cancer Prevention, National Institutes of Health, Executive Boulevard 6130, Rockville, 20892, Maryland, USA

    John A. Milner

  2. Nutritional and Cancer Biology, BIO5 Institute and Center for Toxicology, The University of Arizona, Tucson, 85721-0038, Arizona, USA

    Donato F. Romagnolo

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Fleet, J.C. (2010). Vitamin D and Cancer Chemoprevention. In: Milner, J., Romagnolo, D. (eds) Bioactive Compounds and Cancer. Nutrition and Health. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-60761-627-6_17

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  • DOI: https://doi.org/10.1007/978-1-60761-627-6_17

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  • Publisher Name: Humana Press, Totowa, NJ

  • Print ISBN: 978-1-60761-626-9

  • Online ISBN: 978-1-60761-627-6

  • eBook Packages: MedicineMedicine (R0)

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