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Vitamin D for Cancer Prevention and Survival

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Abstract

Higher levels of the principal circulating form of vitamin D, 25-hydroxyvitamin D (25(OH)D), are associated with substantially lower incidence and death rates from colon, breast, and ovarian cancer, with a linear dose–response gradient. The accumulated evidence from observational studies and a randomized trial reveal that population serum levels of 25(OH)D in the range of 40 to 50 ng/ml will markedly reduce incidence and mortality rates of several cancers including those of the breast, colon, and ovary. There is an immediate clinical need for cancer care providers worldwide to assure that a serum 25(OH)D level >40 ng/ml is achieved as soon as feasible after diagnosis of patients with breast and colon cancer, unless specifically contraindicated by pre-existing hypercalcemia. This serum target could be revisited after further rigorous studies are performed, but the evidence that has accumulated during the past 29 years is sufficiently strong now to adopt the above dosages and serum targets for professional and public health action. Such prompt action is likely to cut mortality from these cancers by half within approximately 5 years. Research on a wider range of cancer types with higher serum 25(OH)D levels (≥50 ng/ml or 125 nmol/l) is needed. In the meantime, vitamin D3 intake by everyone in the continental US and Canada aged 1 year and older should not be less than 2000 IU/day of vitamin D3, and 1000 IU/day for infants.

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References

  1. Garland CF, Garland FC, Gorham ED, Lipkin M, Newmark H, Mohr SB, et al. The role of vitamin D in cancer prevention. Am J Public Health. 2006;96:252–61.

    Article  PubMed  Google Scholar 

  2. Holick MF. Vitamin D status: measurement, interpretation, and clinical application. Ann Epidemiol. 2009 (in press).

  3. Gorham E, Garland C, Garland F. Acid haze air pollution and breast and colon cancer in 20 Canadian cities. Can J Publ Health. 1989;80:96–100.

    CAS  Google Scholar 

  4. Garland F, Garland C, Gorham E, Young J Jr. Geographic variation in breast cancer mortality in the United States: a hypothesis involving exposure to solar radiation. Prev Med. 1990;19:614–22.

    Article  PubMed  CAS  Google Scholar 

  5. Gorham ED, Garland FC, Garland CF. Sunlight and breast cancer incidence in the USSR. Int J Epidemiol. 1990;19:820–4.

    Article  PubMed  CAS  Google Scholar 

  6. Grant WB. An estimate of premature cancer mortality in the U.S. due to inadequate doses of solar ultraviolet-B radiation. Cancer. 2002;94:1867–75.

    Article  PubMed  Google Scholar 

  7. Grant WB. An ecologic study of dietary and solar ultraviolet-B links to breast carcinoma mortality rates. Cancer. 2002;94:272–81.

    Article  PubMed  Google Scholar 

  8. Freedman D, Dosemeci M, McGlynn K. Sunlight and mortality from breast, ovarian, colon, prostate, and non-melanoma skin cancer: a composite death certificate based case-control study. Occup Environ Med. 2002;59:257–62.

    Article  PubMed  CAS  Google Scholar 

  9. Boscoe FP, Schymura MJ. Solar ultraviolet-B exposure and cancer incidence and mortality in the United States, 1993–2002. BMC Cancer. 2006;6:264.

    Article  PubMed  CAS  Google Scholar 

  10. 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.

    Article  PubMed  CAS  Google Scholar 

  11. Bertone-Johnson ER, Chen WY, Holick MF, Hollis BW, Colditz GA, Willett WC, et al. Plasma 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D and risk of breast cancer. Cancer Epidemiol Biomarkers Prev. 2005;14:1991–7.

    Article  PubMed  CAS  Google Scholar 

  12. Abbas S, Linseisen J, Slanger T, Kropp S, Mutschelknauss EJ, Flesch-Janys D, et al. Serum 25-hydroxyvitamin D and risk of post-menopausal breast cancer—results of a large case-control study. Carcinogenesis. 2008;29:93–9.

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  14. Garland C, Shekelle RB, Barrett-Connor E, Criqui MH, Rossof AH, Paul O. Dietary vitamin D and calcium and risk of colorectal cancer: a 19-year prospective study in men. Lancet. 1985;1:307–9.

    Article  PubMed  CAS  Google Scholar 

  15. Garland C, Comstock G, Garland F, Helsing K, Shaw E, Gorham E. Serum 25-hydroxyvitamin D and colon cancer: eight-year prospective study. Lancet. 1989;2:1176–8.

    Article  PubMed  CAS  Google Scholar 

  16. Mizoue T. Ecological studies of solar radiation and cancer mortality in Japan. Health Phys. 2004;87:532–8.

    Article  PubMed  CAS  Google Scholar 

  17. Feskanich D, Ma J, Fuchs CS, Kirkner GJ, Hankinson SE, Hollis BW, et al. Plasma vitamin D metabolites and risk of colorectal cancer in women. Cancer Epidemiol Biomarkers Prev. 2004;13:1502–8.

    PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  19. Wactawski-Wende J, Kotchen JM, Anderson GL, Assaf AR, Brunner RL, O’Sullivan MJ, et al. Calcium plus vitamin D supplementation and the risk of colorectal cancer. N Engl J Med. 2006;354:684–96.

    Article  PubMed  CAS  Google Scholar 

  20. Lefkowitz ES, Garland CF. Sunlight, vitamin D, and ovarian cancer mortality rates in US women. Int J Epidemiol. 1994;23:1133–6.

    Article  PubMed  CAS  Google Scholar 

  21. Mohr SB, Garland CF, Gorham ED, Grant WB, Garland FC. Relationship between low ultraviolet B irradiance and higher breast cancer risk in 107 countries. Breast J. 2008;14:255–60.

    Article  PubMed  Google Scholar 

  22. Tworoger SS, Lee IM, Buring JE, Rosner B, Hollis BW, Hankinson SE. Plasma 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D and risk of incident ovarian cancer. Cancer Epidemiol Biomarkers Prev. 2007;16:783–8.

    Article  PubMed  CAS  Google Scholar 

  23. Grant W, Garland C. The association of solar ultraviolet B with reducing risk of cancer: multifactorial ecological analysis of geographic variation in age-adjusted cancer mortality rates. Anticancer Res. 2006;26:2687–99.

    PubMed  CAS  Google Scholar 

  24. Grant WB. Ecologic studies of solar UV-B radiation and cancer mortality rates. Recent Results Cancer Res. 2003;164:371–7.

    PubMed  CAS  Google Scholar 

  25. Martinez ME, Giovannucci EL, Colditz GA, Stampfer MJ, Hunter DJ, Speizer FE, et al. Calcium, vitamin D, and the occurrence of colorectal cancer among women. J Natl Cancer Inst. 1996;88:1375–82.

    Article  PubMed  CAS  Google Scholar 

  26. Kearney J, Giovannucci E, Rimm EB, Ascherio A, Stampfer MJ, Colditz GA, et al. Calcium, vitamin D, and dairy foods and the occurrence of colon cancer in men. Am J Epidemiol. 1996;143:907–17.

    PubMed  CAS  Google Scholar 

  27. Pritchard RS, Baron JA, Gerhardsson de Verdier M. Dietary calcium, vitamin D, and the risk of colorectal cancer in Stockholm, Sweden. Cancer Epidemiol Biomarkers Prev. 1996;5:897–900.

    PubMed  CAS  Google Scholar 

  28. LaVecchia C, Braga C, Negri E, Francesci S, Russo A, et al. Intake of selected micronutrients and risk of colorectal cancer. Int J Cancer. 1997;73:525–30.

    Article  CAS  Google Scholar 

  29. Salazar-Martinez E, Lazcano-Ponce EC, Gonzalez Lira-Lira G, Escudero-De los Rios P, Hernandez-Avila M. Nutritional determinants of epithelial ovarian cancer risk: a case-control study in Mexico. Oncology. 2002;63:151–7.

    Article  PubMed  CAS  Google Scholar 

  30. Salazar-Martinez E, Lazcano-Ponce E, Sanchez-Zamorano LM, Gonzalez-Lira G, Escudero DELRP, Hernandez-Avila M. Dietary factors and endometrial cancer risk. Results of a case-control study in Mexico. Int J Gynecol Cancer. 2005;15:938–45.

    Article  PubMed  CAS  Google Scholar 

  31. Lin J, Manson JE, Lee IM, Cook NR, Buring JE, Zhang SM. Intakes of calcium and vitamin D and breast cancer risk in women. Arch Intern Med. 2007;167:1050–9.

    Article  PubMed  CAS  Google Scholar 

  32. John E, Schwartz G, Dreon D, Koo J. Vitamin D and breast cancer risk: The NHANES I epidemiologic follow-up study, 1971–1975 to 1992. Cancer Epidemiol Biomarkers Prev. 1999;8:399–406.

    PubMed  CAS  Google Scholar 

  33. John EM, Dreon DM, Koo J, Schwartz GG. Residential sunlight exposure is associated with a decreased risk of prostate cancer. J Steroid Biochem Mol Biol. 2004;89–90:549–52.

    Article  PubMed  CAS  Google Scholar 

  34. John EM, Koo J, Schwartz GG. Sun exposure and prostate cancer risk: evidence for a protective effect of early-life exposure. Cancer Epidemiol Biomarkers Prev. 2007;16:1283–6.

    Article  PubMed  Google Scholar 

  35. Lappe JM, Travers-Gustafson D, Davies KM, Recker RR, Heaney RP. Vitamin D and calcium supplementation reduces cancer risk: results of a randomized trial. Am J Clin Nutr. 2007;85:1586–91.

    PubMed  CAS  Google Scholar 

  36. Garland C, Grant W, Mohr S, Gorham E, Garland F. What is the dose-response relationship between vitamin D and cancer risk? Nutr Rev. 2007;65:S91–5.

    Article  PubMed  Google Scholar 

  37. Abbas S, Chang-Claude J, Linseisen J. Plasma 25-hydroxyvitamin D and premenopausal breast cancer risk in a German case-control study. Int J Cancer. 2009;124:250–5.

    Article  PubMed  CAS  Google Scholar 

  38. Garland CF, Gorham ED, Mohr SB, Grant WB, Giovannucci EL, Lipkin M, et al. Vitamin D and prevention of breast cancer: pooled analysis. J Steroid Biochem Mol Biol. 2007;103:708–11.

    Article  PubMed  CAS  Google Scholar 

  39. Hill AB. The environment and disease: association or causation? Proc R Soc Med. 1965;58:295–300.

    PubMed  CAS  Google Scholar 

  40. Lipkin M, Newmark HL. Vitamin D, calcium and prevention of breast cancer: a review. J Am Coll Nutr. 1999;18:392S–7S.

    PubMed  CAS  Google Scholar 

  41. Brenner B, Russell N, Albrecht S, Davies R. The effect of dietary vitamin D3 on the intracellular calcium gradient in mammalian colonic crypts. Cancer Lett. 1998;12:43–53.

    Article  Google Scholar 

  42. Tangpricha V, Flanagan JN, Whitlatch LW, Tseng CC, Chen TC, Holt PR, et al. 25-hydroxyvitamin D-1alpha-hydroxylase in normal and malignant colon tissue. Lancet. 2001;357:1673–4.

    Article  PubMed  CAS  Google Scholar 

  43. Cross HS, Lipkin M, Kallay E. Nutrients regulate the colonic vitamin D system in mice: relevance for human colon malignancy. J Nutr. 2006;136:561–4.

    PubMed  CAS  Google Scholar 

  44. Freedman DM, Looker AC, Chang SC, Graubard BI. Prospective study of serum vitamin D and cancer mortality in the United States. J Natl Cancer Inst. 2007;99:1594–602.

    Article  PubMed  CAS  Google Scholar 

  45. Chlebowski R, Johnson K, Kooperberg C, et al. Calcium plus vitamin D supplementation and the risk of breast cancer. J Natl Cancer Inst. 2008;100:1581–91.

    Article  PubMed  CAS  Google Scholar 

  46. Liel Y, Ulmer E, Shary J, Hollis BW, Bell NH. Low circulating vitamin D in obesity. Calcif Tissue Int. 1988;43:199–201.

    Article  PubMed  CAS  Google Scholar 

  47. Snijder MB, van Dam RM, Visser M, Deeg DJ, Dekker JM, Bouter LM, et al. Adiposity in relation to vitamin D status and parathyroid hormone levels: a population-based study in older men and women. J Clin Endocrinol Metab. 2005;90:4119–23.

    Article  PubMed  CAS  Google Scholar 

  48. Scragg R, Camargo CA Jr. Frequency of leisure-time physical activity and serum 25-hydroxyvitamin D levels in the US population: results from the Third National Health and Nutrition Examination Survey. Am J Epidemiol. 2008;168:577–86.

    Article  PubMed  Google Scholar 

  49. Hiatt R, Krieger N, Lobaugh B, Drezner M, Vogelman J, Orentreich N. Prediagnostic serum vitamin D and breast cancer. J Natl Cancer Inst. 1998;90:461–3.

    Article  PubMed  CAS  Google Scholar 

  50. Janowsky EC, Lester GE, Weinberg CR, Millikan RC, Schildkraut JM, Garrett PA, et al. Association between low levels of 1,25-dihydroxyvitamin D and breast cancer risk. Public Health Nutr. 1999;2:283–91.

    Article  PubMed  CAS  Google Scholar 

  51. Freedman DM, Chang SC, Falk RT, Purdue MP, Huang WY, McCarty CA, et al. Serum levels of vitamin D metabolites and breast cancer risk in the prostate, lung, colorectal, and ovarian cancer screening trial. Cancer Epidemiol Biomarkers Prev. 2008;17:889–94.

    Article  PubMed  CAS  Google Scholar 

  52. Garland CF, Gorham ED, Baggerly CA, Garland FC. Re: Prospective study of vitamin D and cancer mortality in the United States. J Natl Cancer Inst. 2008;100:826–7.

    PubMed  Google Scholar 

  53. Braun MM, Helzlsouer KJ, Hollis BW, Comstock GW. Colon cancer and serum vitamin D metabolite levels 10–17 years prior to diagnosis. Am J Epidemiol. 1995;142:608–11.

    PubMed  CAS  Google Scholar 

  54. Gorham ED, Garland CF, Garland FC, Grant WB, Mohr SB, Lipkin M, et al. Optimal vitamin D status for colorectal cancer prevention: a quantitative meta analysis. Am J Prev Med. 2007;32:210–6.

    Article  PubMed  Google Scholar 

  55. Garland CF, Mohr SB, Gorham ED, Grant WB, Garland FC. Role of ultraviolet B irradiance and vitamin D in prevention of ovarian cancer. Am J Prev Med. 2006;31:512–4.

    Article  PubMed  Google Scholar 

  56. Mohr SB, Garland CF, Gorham ED, Grant WB, Garland FC. Is ultraviolet B irradiance inversely associated with incidence rates of endometrial cancer?: an ecological study of 107 countries. Prev Med. 2007;45:327–31.

    Article  PubMed  CAS  Google Scholar 

  57. Mohr SB, Gorham ED, Garland CF, Grant WB, Garland FC. Are low ultraviolet B and high animal protein intake associated with risk of renal cancer? Int J Cancer. 2006;119:2705–9.

    Article  PubMed  CAS  Google Scholar 

  58. Mohr S, Gorham E, Garland C, Grant W, Garland F. Are low UVB and high animal energy intake associated UVB and vitamin D higher incidence rates of renal cancer? Int J Cancer. 2006;120.

  59. Stolzenberg-Solomon RZ, Vieth R, Azad A, Pietinen P, Taylor PR, Virtamo J, et al. A prospective nested case-control study of vitamin d status and pancreatic cancer risk in male smokers. Cancer Res. 2006;66:10213–9.

    Article  PubMed  CAS  Google Scholar 

  60. Abnet CC, Chen W, Dawsey SM, Wei WQ, Roth MJ, Liu B, et al. Serum 25(OH)-vitamin D concentration and risk of esophageal squamous dysplasia. Cancer Epidemiol Biomarkers Prev. 2007;16:1889–93.

    Article  PubMed  CAS  Google Scholar 

  61. Knekt P, Jarvinen R, Dich J, Hakulinen T. Risk of colorectal and other gastro-intestinal cancers after exposure to nitrate, nitrite and N-nitroso compounds: a follow-up study. Int J Cancer. 1999;80:852–6.

    Article  PubMed  CAS  Google Scholar 

  62. Zou XN, Lu SH, Liu B. Volatile N-nitrosamines and their precursors in Chinese salted fish—a possible etological factor for NPC in china. Int J Cancer. 1994;59:155–8.

    Article  PubMed  CAS  Google Scholar 

  63. Dallorso ME, Gil S, Pawlak E, Lema F, Marquez A. 1,25(OH)2 vitamin D concentration in the plasma of Solanum glaucophyllum intoxicated rabbits. Aust Vet J. 2001;79:419–23.

    Article  PubMed  CAS  Google Scholar 

  64. Ding EL, Mehta S, Fawzi WW, Giovannucci EL. 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. 2008;122:1690–4.

    Article  PubMed  CAS  Google Scholar 

  65. Pratt W, Taylor P, Goldstein A. Principles of drug action: the basis of pharmacology. New York: Churchill Livingstone; 1990.

    Google Scholar 

  66. Mohr S, Garland C, Gorham E, Grant W, Highfill R, Garland F. Mapping vitamin D deficiency, breast cancer and colorectal cancer. Proceedings of the ESRI international user conference, San Diego, CA; 2005. p. 1778.

  67. Goodwin P, Ennis M, Pritchard K, Koo J, Hood N, Lunenfeld S, et al. Vitamin D deficiency is common at breast cancer diagnosis and is associated with a significantly higher risk of distant recurrence and death in a prospective cohort study of T1-3, N0-1, M0 BC (abstract). American Society for Clinical Oncology Annual Meeting, Chicago, IL, May 17, 2008.

  68. Ng K, Meyerhardt JA, Wu K, Feskanich D, Hollis BW, Giovannucci EL, et al. Circulating 25-hydroxyvitamin d levels and survival in patients with colorectal cancer. J Clin Oncol. 2008;26:2984–91.

    Article  PubMed  CAS  Google Scholar 

  69. Porojnicu AC, Dahlback A, Moan J. Sun exposure and cancer survival in Norway: changes in the risk of death with season of diagnosis and latitude. Adv Exp Med Biol. 2008;624:43–54.

    Article  PubMed  Google Scholar 

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

    Article  PubMed  Google Scholar 

  71. Stryd RP, Gilbertson TJ, Brunden MN. A seasonal variation study of 25-hydroxyvitamin D3 serum levels in normal humans. J Clin Endocrinol Metab. 1979;48:771–5.

    PubMed  CAS  Google Scholar 

  72. Garland C, Gorham, Mohr S, Grant W, Garland F. Pooled analysis of vitamin D and breast cancer. American Association for Cancer Research Annual Meeting, San Diego, CA; 2008.

  73. Ferlay J, Bray F, Pisani P, Parkin D. GLOBOCAN 2002: cancer incidence, mortality and prevalence worldwide. IARC CancerBase No. 5. version 2.0. http://www-dep.iarc.fr/ (2008). Accessed 10 July 2008.

  74. Columbia University: Center for International Earth Science Information Network. http://sedac.ciesin.columbia.edu/ozone/rtm/mval.html (2008). Accessed 10 July 2008.

  75. National Aeronautics and Space Administration. International Satellite Cloud Climatology Project database. http://isccp.giss.nasa.gov/products/isccpDsets.html. Accessed 31 December 2008.

  76. National Academy of Sciences—Institute of Medicine, Food, Nutrition Board. Dietary reference intakes for calcium, phosphorus, magnesium, vitamin D, and fluoride. Washington, DC: National Academy Press; 1997.

    Google Scholar 

  77. Coleman MP, Quaresma M, Berrino F, Lutz JM, De Angelis R, Capocaccia R, et al. Cancer survival in five continents: a worldwide population-based study (CONCORD). Lancet Oncol. 2008;9:730–56.

    Article  PubMed  Google Scholar 

  78. Vilenchik MM, Knudson AG. Radiation dose-rate effects, endogenous DNA damage, and signaling resonance. Proc Natl Acad Sci U S A. 2006;103:17874–9.

    Article  PubMed  CAS  Google Scholar 

  79. Cairns J. Somatic stem cells and the kinetics of mutagenesis and carcinogenesis. Proc Natl Acad Sci U S A. 2002;99:10567–70.

    Article  PubMed  CAS  Google Scholar 

  80. Jones S, Chen WD, Parmigiani G, Diehl F, Beerenwinkel N, Antal T, et al. Comparative lesion sequencing provides insights into tumor evolution. Proc Natl Acad Sci USA. 2008;105:4283–8.

    Article  PubMed  CAS  Google Scholar 

  81. Gumbiner BM. Cell adhesion: the molecular basis of tissue architecture and morphogenesis. Cell. 1996;84:345–57.

    Article  PubMed  CAS  Google Scholar 

  82. Hay ED. An overview of epithelio-mesenchymal transformation. Acta Anat. 1995;154:8–20.

    Article  PubMed  CAS  Google Scholar 

  83. Pearson GW, Hunter T. Real-time imaging reveals that noninvasive mammary epithelial acini can contain motile cells. J Cell Biol. 2007;179:1555–67.

    Article  PubMed  CAS  Google Scholar 

  84. Gradstein F, Ogg J, Smith A. A geologic time scale. Cambridge: Cambridge University Press; 2004.

    Google Scholar 

  85. Wicha MS. Identification of murine mammary stem cells: implications for studies of mammary development and carcinogenesis. Breast Cancer Res. 2006;8:109.

    PubMed  Google Scholar 

  86. Shimkin M. Contrary to nature. Bethesda, MD: U.S. Department of Health, Education and Welfare; 1979.

    Google Scholar 

  87. Liu S, Dontu G, Wicha MS. Mammary stem cells, self-renewal pathways, and carcinogenesis. Breast Cancer Res. 2005;7:86–95.

    Article  PubMed  CAS  Google Scholar 

  88. Dawkins R. The selfish gene. New York: Oxford University Press; 2006.

    Google Scholar 

  89. Zheng B, Mills AA, Bradley A. Introducing defined chromosomal rearrangements into the mouse genome. Methods. 2001;24:81–94.

    Article  PubMed  CAS  Google Scholar 

  90. Okamura M, Yasuno N, Ohtsuka M, Tanaka A, Shikazono N, Hase Y. Wide variety of color- and shape mutants regenerated from leaf cultures irradiated with ion beams. Nuclear Instruments and Methods in Physics Research B. 2003;206:574–8.

    Article  CAS  Google Scholar 

  91. Eigeliene N, Harkonen P, Erkkola R. Effects of estradiol and medroxyprogesterone acetate on morphology, proliferation and apoptosis of human breast tissue in organ cultures. BMC Cancer. 2006;6:246.

    Article  PubMed  CAS  Google Scholar 

  92. Ruotsalainen H, Sipila L, Vapola M, Sormunen R, Salo AM, Uitto L, et al. Glycosylation catalyzed by lysyl hydroxylase 3 is essential for basement membranes. J Cell Sci. 2006;119:625–35.

    Article  PubMed  CAS  Google Scholar 

  93. Pitelka DR, Taggart BN, Hamamoto ST. Effects of extracellular calcium depletion on membrane topography and occluding junctions of mammary epithelial cells in culture. J Cell Biol. 1983;96:613–24.

    Article  PubMed  CAS  Google Scholar 

  94. Contreras RG, Miller JH, Zamora M, Gonzalez-Mariscal L, Cereijido M. Interaction of calcium with plasma membrane of epithelial (MDCK) cells during junction formation. Am J Physiol. 1992;263:C313–8.

    PubMed  CAS  Google Scholar 

  95. Whelan J, McEntee MF. Dietary (n-6) PUFA and intestinal tumorigenesis. J Nutr. 2004;134:3421S–6S.

    PubMed  CAS  Google Scholar 

  96. Raimondi F, Santoro P, Barone MV, Pappacoda S, Barretta ML, Nanayakkara M, et al. Bile acids modulate tight junction structure and barrier function of Caco-2 monolayers via EGFR activation. Am J Physiol Gastrointest Liver Physiol. 2008;294:G906–13.

    Article  PubMed  CAS  Google Scholar 

  97. Debruyne PR, Bruyneel EA, Li X, Zimber A, Gespach C, Mareel MM. The role of bile acids in carcinogenesis. Mutat Res. 2001;480–481:359–69.

    PubMed  Google Scholar 

  98. Newmark H, Wargovich M, Bruce W. Colon cancer, and dietary fat, phosphate, and calcium: a hypothesis. JNCI. 1984;72:1321–5.

    Google Scholar 

  99. Pettifor JM. Vitamin D and/or calcium deficiency rickets in infants and children: a global perspective. Indian J Med Res. 2008;127:245–9.

    PubMed  CAS  Google Scholar 

  100. Kutluk G, Cetinkaya F, Basak M. Comparisons of oral calcium, high dose vitamin D and a combination of these in the treatment of nutritional rickets in children. J Trop Pediatr. 2002;48:351–3.

    Article  PubMed  Google Scholar 

  101. Garland C, Garland F, Gorham E. Colon cancer parallels rickets. In: Lipkin M, Newmark H, Kelloff G, editors. Calcium, vitamin D, and prevention of colon cancer. Bethesda, MD/Boca Raton, FL: National Cancer Institute/CRC Press; 1991. p. 81–109.

    Google Scholar 

  102. Murillo G, Matusiak D, Benya RV, Mehta RG. Chemopreventive efficacy of 25-hydroxyvitamin D3 in colon cancer. J Steroid Biochem Mol Biol. 2007;103:763–7.

    Article  PubMed  CAS  Google Scholar 

  103. Vantieghem K, Overbergh L, Carmeliet G, De Haes P, Bouillon R, Segaert S. UVB-induced 1, 25(OH)2D3 production and vitamin D activity in intestinal CaCo-2 cells and in THP-1 macrophages pretreated with a sterol Delta7-reductase inhibitor. J Cell Biochem. 2006;99:229–40.

    Article  PubMed  CAS  Google Scholar 

  104. Broe KE, Chen TC, Weinberg J, Bischoff-Ferrari HA, Holick MF, Kiel DP. A higher dose of vitamin D reduces the risk of falls in nursing home residents: a randomized, multiple-dose study. J Am Geriatr Soc. 2007;55:234–9.

    Article  PubMed  Google Scholar 

  105. Talwar SA, Aloia JF, Pollack S, Yeh JK. Dose response to vitamin D supplementation among postmenopausal African American women. Am J Clin Nutr. 2007;86:1657–62.

    PubMed  CAS  Google Scholar 

  106. Aloia JF, Talwar SA, Pollack S, Yeh J. A randomized controlled trial of vitamin D3 supplementation in African American women. Arch Intern Med. 2005;165:1618–23.

    Article  PubMed  CAS  Google Scholar 

  107. Wicklow BA, Taback SP. Feasibility of a type 1 diabetes primary prevention trial using 2000 IU vitamin D3 in infants from the general population with increased HLA-associated risk. Ann N Y Acad Sci. 2006;1079:310–2.

    Article  PubMed  CAS  Google Scholar 

  108. Saadi HF, Dawodu A, Afandi BO, Zayed R, Benedict S, Nagelkerke N. Efficacy of daily and monthly high-dose calciferol in vitamin D-deficient nulliparous and lactating women. Am J Clin Nutr. 2007;85:1565–71.

    PubMed  CAS  Google Scholar 

  109. Basile LA, Taylor SN, Wagner CL, Horst RL, Hollis BW. The effect of high-dose vitamin D supplementation on serum vitamin D levels and milk calcium concentration in lactating women and their infants. Breastfeed Med. 2006;1:27–35.

    Article  PubMed  Google Scholar 

  110. Kislal FM, Dilmen U. Effect of different doses of vitamin D on osteocalcin and deoxypyridinoline in preterm infants. Pediatr Int. 2008;50:204–7.

    Article  PubMed  CAS  Google Scholar 

  111. Hathcock JN, Shao A, Vieth R, Heaney R. Risk assessment for vitamin D. Am J Clin Nutr. 2007;85:6–18.

    PubMed  CAS  Google Scholar 

  112. Vieth R. The risk of additional vitamin D. Ann Epidemiol. 2008 (in press).

  113. Heaney RP, Davies KM, Chen TC, Holick MF, Barger-Lux MJ. Human serum 25-hydroxycholecalciferol response to extended oral dosing with cholecalciferol. Am J Clin Nutr. 2003;77:204–10.

    PubMed  CAS  Google Scholar 

  114. Vieth R. Vitamin D supplementation, 25-hydroxyvitamin D concentrations, and safety. Am J Clin Nutr. 1999;69:842–56.

    PubMed  CAS  Google Scholar 

  115. Vieth R, Chan PC, MacFarlane GD. Efficacy and safety of vitamin D3 intake exceeding the lowest observed adverse effect level. Am J Clin Nutr. 2001;73:288–94.

    PubMed  CAS  Google Scholar 

  116. Vieth R. Critique of the consideration for establishing the for vitamin D tolerable intake: critical need for revision. J Nutr. 2006;136:1117–22.

    PubMed  CAS  Google Scholar 

  117. Armas LA, Hollis BW, Heaney RP. Vitamin D2 is much less effective than vitamin D3 in humans. J Clin Endocrinol Metab. 2004;89:5387–91.

    Article  PubMed  CAS  Google Scholar 

  118. Holick MF, Biancuzzo RM, Chen TC, Klein EK, Young A, Bibuld D, et al. Vitamin D2 is as effective as vitamin D3 in maintaining circulating concentrations of 25-hydroxyvitamin D. J Clin Endocrinol Metab. 2008;93:677–81.

    Article  PubMed  CAS  Google Scholar 

  119. Hall PM. Preventing kidney stones: calcium restriction not warranted. Cleve Clin J Med. 2002;69:885–8.

    Article  PubMed  Google Scholar 

  120. Meschi T, Schianchi T, Ridolo E, Adorni G, Allegri F, Guerra A, et al. Body weight, diet and water intake in preventing stone disease. Urol Int. 2004;72(1):29–33.

    Article  PubMed  CAS  Google Scholar 

  121. Pak CY. Medical stone management: 35 years of advances. J Urol. 2008;180:813–9.

    Article  PubMed  CAS  Google Scholar 

  122. Spivacow FR, Negri AL, del Valle EE, Calvino I, Fradinger E, Zanchetta JR. Metabolic risk factors in children with kidney stone disease. Pediatr Nephrol. 2008;23:1129–33.

    Article  PubMed  Google Scholar 

  123. Massey LK. Dietary influences on urinary oxalate and risk of kidney stones. Front Biosci. 2003;8:s584–94.

    Article  PubMed  CAS  Google Scholar 

  124. Kramer HJ, Choi HK, Atkinson K, Stampfer M, Curhan GC. The association between gout and nephrolithiasis in men: the health professionals’ follow-up study. Kidney Int. 2003;64:1022–6.

    Article  PubMed  Google Scholar 

  125. Cramer JS, Forrest K. Renal lithiasis: addressing the risks of austere desert deployments. Aviat Space Environ Med. 2006;77:649–53.

    PubMed  Google Scholar 

  126. Curhan GC. Dietary calcium, dietary protein, and kidney stone formation. Miner Electrolyte Metab. 1997;23:261–4.

    PubMed  CAS  Google Scholar 

  127. Scragg R, Jackson R, Holdaway I, Lim T, Beaglehole R. Myocardial infarction is inversely associated with plasma 25-hydroxyvitamin D3 levels: a community-based study. Int J Epidemiol. 1990;19:559–63.

    Article  PubMed  CAS  Google Scholar 

  128. Giovannucci E, Liu Y, Hollis BW, Rimm EB. 25-hydroxyvitamin D and risk of myocardial infarction in men: a prospective study. Arch Intern Med. 2008;168:1174–80.

    Article  PubMed  CAS  Google Scholar 

  129. Hypponen E, Laara E, Reunanen A, Jarvelin MR, Virtanen SM. Intake of vitamin D and risk of type 1 diabetes: a birth-cohort study. Lancet. 2001;358:1500–3.

    Article  PubMed  CAS  Google Scholar 

  130. Mohr SB, Garland CF, Gorham ED, Garland FC. The association between ultraviolet B irradiance, vitamin D status and incidence rates of type 1 diabetes in 51 regions worldwide. Diabetologia. 2008;51:1391–8.

    Article  PubMed  CAS  Google Scholar 

  131. Goldberg P, Fleming MC, Picard EH. Multiple sclerosis: decreased relapse rate through dietary supplementation with calcium, magnesium and vitamin D. Med Hypotheses. 1986;21:193–200.

    Article  PubMed  CAS  Google Scholar 

  132. Munger KL, Levin LI, Hollis BW, Howard NS, Ascherio A. Serum 25-hydroxyvitamin D levels and risk of multiple sclerosis. JAMA. 2006;296:2832–8.

    Article  PubMed  CAS  Google Scholar 

  133. Webb AR, Kline L, Holick MF. 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. 1988;67:373–8.

    Article  PubMed  CAS  Google Scholar 

  134. Vieth R, Bischoff-Ferrari H, Boucher BJ, Dawson-Hughes B, Garland CF, Heaney RP, et al. The urgent need to recommend an intake of vitamin D that is effective. Am J Clin Nutr. 2007;85:649–50.

    PubMed  CAS  Google Scholar 

  135. Kakarala RR, Chandana SR, Harris SS, Kocharla LP, Dvorin E. Prevalence of vitamin D deficiency in uninsured women. J Gen Intern Med. 2007;22:1180–3.

    Article  PubMed  Google Scholar 

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Acknowledgments

This research was partially supported by a Special Interest Congressional Project allocation to the Penn State Cancer Institute of the Milton S. Hersey Medical Center, Hershey, PA, USA, through the Department of the Navy, Bureau of Medicine and Surgery, and the Naval Health Research Center in San Diego, CA, USA, Work Unit No. 60126.

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Authors and Affiliations

  1. Department of Family and Preventive Medicine, University of California, San Diego, 9500 Gilman Drive 0631C, La Jolla, CA, 92093-0631, USA

    Edward D. Gorham, Sharif B. Mohr, Frank C. Garland & Cedric F. Garland

  2. Naval Health Research Center, 140 Sylvester Road, San Diego, CA, 92106-3521, USA

    Edward D. Gorham, Sharif B. Mohr, Frank C. Garland & Cedric F. Garland

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  1. Edward D. Gorham
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  2. Sharif B. Mohr
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  4. Cedric F. Garland
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Correspondence to Edward D. Gorham.

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The views expressed in this report are those of the authors and do not represent an official position of the Department of the Navy, Department of Defense, or the US Government.

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Gorham, E.D., Mohr, S.B., Garland, F.C. et al. Vitamin D for Cancer Prevention and Survival. Clinic Rev Bone Miner Metab 7, 159–175 (2009). https://doi.org/10.1007/s12018-009-9028-8

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