Toggle Health Problems and D

Breast Cancer is prevented by vitamin D – but more RCT are needed to understand why – April 2015

Vitamin D and Reduction of Breast Cancer Risk

Current Breast Cancer Reports, April 2015
Jennifer K. Lue, Katherine D. Crew


VitaminDWiki - over a dozen meta-analysis agree - how much data do they need?

Overview Breast Cancer and Vitamin D

Pages listed in BOTH Breast Cancer AND Meta-analysis


Vitamin D is not only essential in bone metabolism and calcium homeostasis but also has anticarcinogenic properties in multiple malignancies, including breast cancer. Vitamin D deficiency is a potentially modifiable risk factor that may be easily targeted for breast cancer risk reduction through supplementation. Several epidemiological studies have demonstrated an inverse relationship between dietary intake and blood levels of vitamin D and breast cancer risk; however, the results have been inconsistent. Despite some promising findings, further randomized controlled trials of vitamin D supplements are needed to determine the role of vitamin D in breast cancer prevention.

This article is part of the Topical Collection on Risk, Prevention, and Screening

References

  1. Siegel, R, Naishadham, D, Jemal, A (2012) Cancer statistics, 2012. CA Cancer J Clin 62: pp. 10-29 CrossRef
  2. Jemal, A (2011) Global cancer statistics. Ca-a Cancer J Clin 61: pp. 69-90 CrossRef
  3. Studzinski, GP, Moore, DC (1995) Sunlight—can it prevent as well as cause cancer?. Cancer Res 55: pp. 4014-22
  4. Gorham, ED, Garland, FC, Garland, CF (1990) Sunlight and breast cancer incidence in the USSR. Int J Epidemiol 19: pp. 820-4 CrossRef
  5. Garland, FC (1990) Geographic variation in breast cancer mortality in the United States: a hypothesis involving exposure to solar radiation. Prev Med 19: pp. 614-22 CrossRef
  6. Blot, WJ, Fraumeni, JF, Stone, BJ (1977) Geographic patterns of breast cancer in the United States. J Natl Cancer Inst 59: pp. 1407-11
  7. Welsh, J (2004) Vitamin D and breast cancer: insights from animal models. Am J Clin Nutr 80: pp. 1721S-4S
  8. Looker, AC (2008) Serum 25-hydroxyvitamin D status of the US population: 1988–1994 compared with 2000–2004. Am J Clin Nutr 88: pp. 1519-27 CrossRef
  9. Wortsman, J (2000) Decreased bioavailability of vitamin D in obesity. Am J Clin Nutr 72: pp. 690-3
  10. Giovannucci, E (2008) Vitamin D status and cancer incidence and mortality. Adv Exp Med Biol 624: pp. 31-42 CrossRef
  11. Hewison, M (2000) 1alpha-Hydroxylase and the action of vitamin D. J Mol Endocrinol 25: pp. 141-8 CrossRef
  12. Schwartz, GG (1998) Human prostate cells synthesize 1,25-dihydroxyvitamin D3 from 25-hydroxyvitamin D3. Cancer Epidemiol Biomarkers Prev 7: pp. 391-5
  13. Carlberg, C, Dunlop, TW (2006) The impact of chromatin organization of vitamin D target genes. Anticancer Res 26: pp. 2637-45
  14. Colston, KW, Hansen, CM (2002) Mechanisms implicated in the growth regulatory effects of vitamin D in breast cancer. Endocr Relat Cancer 9: pp. 45-59 CrossRef
  15. Feldman, D (2014) The role of vitamin D in reducing cancer risk and progression. Nat Rev Cancer 14: pp. 342-57 CrossRef
  16. Abbas, S, Linseisen, J, Chang-Claude, J (2007) Dietary vitamin D and calcium intake and premenopausal breast cancer risk in a German case-control study. Nutr Cancer 59: pp. 54-61 CrossRef
  17. Levi, F (2001) Dietary intake of selected micronutrients and breast-cancer risk. Int J Cancer 91: pp. 260-3 CrossRef
  18. Potischman, N (1999) Intake of food groups and associated micronutrients in relation to risk of early-stage breast cancer. Int J Cancer 82: pp. 315-21 CrossRef
  19. Rossi, M (2009) Vitamin D intake and breast cancer risk: a case-control study in Italy. Ann Oncol 20: pp. 374-8 CrossRef
  20. Simard, A, Vobecky, J, Vobecky, JS (1991) Vitamin D deficiency and cancer of the breast: an unprovocative ecological hypothesis. Can J Public Health 82: pp. 300-3
  21. Frazier AL et al. Adolescent diet and risk of breast cancer. Cancer Causes Control. 2004;15(1):73–82.
  22. John, EM, Vitamin, D (1999) Vitamin D and breast cancer risk: the NHANES I Epidemiologic follow-up study, 1971–1975 to 1992. National Health and Nutrition Examination Survey. Cancer Epidemiol Biomarkers Prev 8: pp. 399-406
  23. Lin, J (2007) Intakes of calcium and vitamin D and breast cancer risk in women. Arch Intern Med 167: pp. 1050-9 CrossRef
  24. McCullough, ML (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: pp. 2898-904 CrossRef
  25. Robien, K, Cutler, GJ, Lazovich, D (2007) Vitamin D intake and breast cancer risk in postmenopausal women: the Iowa Women’s Health Study. Cancer Causes Control 18: pp. 775-82 CrossRef
  26. Shin, MH (2002) Intake of dairy products, calcium, and vitamin d and risk of breast cancer. J Natl Cancer Inst 94: pp. 1301-11 CrossRef
  27. Chen, P (2010) Meta-analysis of vitamin D, calcium and the prevention of breast cancer. Breast Cancer Res Treat 121: pp. 469-77 CrossRef
  28. Frazier, AL (2004) Adolescent diet and risk of breast cancer. Cancer Causes Control 15: pp. 73-82 CrossRef
  29. Kuper, H (2009) Prospective study of solar exposure, dietary vitamin D intake, and risk of breast cancer among middle-aged women. Cancer Epidemiol Biomarkers Prev 18: pp. 2558-61 CrossRef
  30. Gonzalez, CA, Riboli, E (2010) Diet and cancer prevention: contributions from the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Eur J Cancer 46: pp. 2555-62 CrossRef
  31. Edvardsen, K (2011) Vitamin D-effective solar UV radiation, dietary vitamin D and breast cancer risk. Int J Cancer 128: pp. 1425-33 CrossRef
  32. Abbas, S (2013) Dietary intake of vitamin D and calcium and breast cancer risk in the European Prospective Investigation into Cancer and Nutrition. Nutr Cancer 65: pp. 178-87 CrossRef
  33. Kim, Y, Je, Y (2014) Vitamin D intake, blood 25(OH)D levels, and breast cancer risk or mortality: a meta-analysis. Br J Cancer 110: pp. 2772-84 CrossRef
  34. Ross, AC (2011) The 2011 report on dietary reference intakes for calcium and vitamin D from the Institute of Medicine: what clinicians need to know. J Clin Endocrinol Metab 96: pp. 53-8 CrossRef
  35. World Health Organization. Prevention and management of osteoporosis. World Health Organization Technical Report Series. 2003;921:1–164.
  36. Zerwekh, JE (2008) Blood biomarkers of vitamin D status. Am J Clin Nutr 87: pp. 1087S-91S
  37. Holick, MF (2009) Vitamin D status: measurement, interpretation, and clinical application. Ann Epidemiol 19: pp. 73-8 CrossRef
  38. Crew, KD (2009) Association between plasma 25-hydroxyvitamin D and breast cancer risk. Cancer Prev Res (Phila) 2: pp. 598-604 CrossRef
  39. Garland, CF (2007) Vitamin D and prevention of breast cancer: pooled analysis. J Steroid Biochem Mol Biol 103: pp. 708-11 CrossRef
  40. Abbas, S, Chang-Claude, J, Linseisen, J (2009) Plasma 25-hydroxyvitamin D and premenopausal breast cancer risk in a German case-control study. Int J Cancer 124: pp. 250-5 CrossRef
  41. Abbas, S (2008) Serum 25-hydroxyvitamin D and risk of post-menopausal breast cancer—results of a large case-control study. Carcinogenesis 29: pp. 93-9 CrossRef
  42. Freedman, DM (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: pp. 889-94 CrossRef
  43. McCullough, ML (2009) Serum 25-hydroxyvitamin D concentrations and postmenopausal breast cancer risk: a nested case control study in the Cancer Prevention Study-II Nutrition Cohort. Breast Cancer Res 11: pp. R64 CrossRef
  44. Rejnmark, L (2009) Reduced prediagnostic 25-hydroxyvitamin D levels in women with breast cancer: a nested case-control study. Cancer Epidemiol Biomarkers Prev 18: pp. 2655-60 CrossRef
  45. Engel, P (2010) Serum 25(OH) vitamin D and risk of breast cancer: a nested case-control study from the French E3N cohort. Cancer Epidemiol Biomarkers Prev 19: pp. 2341-50 CrossRef
  46. Wang, D (2013) Serum 25-hydroxyvitamin D and breast cancer risk: a meta-analysis of prospective studies. Tumour Biol 34: pp. 3509-17 CrossRef
  47. Ordonez-Mena, JM (2013) Serum 25-hydroxyvitamin d and cancer risk in older adults: results from a large German prospective cohort study. Cancer Epidemiol Biomarkers Prev 22: pp. 905-16 CrossRef
  48. Kuhn, T (2013) Plasma 25-hydroxyvitamin D and the risk of breast cancer in the European prospective investigation into cancer and nutrition: a nested case-control study. Int J Cancer 133: pp. 1689-700 CrossRef
  49. Mohr, SB (2013) Serum 25-hydroxyvitamin D and breast cancer in the military: a case-control study utilizing pre-diagnostic serum. Cancer Causes Control 24: pp. 495-504 CrossRef
  50. Scarmo, S (2013) Circulating levels of 25-hydroxyvitamin D and risk of breast cancer: a nested case-control study. Breast Cancer Res 15: pp. R15 CrossRef
  51. Almquist, M (2010) Serum levels of vitamin D, PTH and calcium and breast cancer risk—a prospective nested case-control study. Int J Cancer 127: pp. 2159-68 CrossRef
  52. Skaaby, T (2014) Prospective population-based study of the association between serum 25-hydroxyvitamin-D levels and the incidence of specific types of cancer. Cancer Epidemiol Biomarkers Prev 23: pp. 1220-9 CrossRef
  53. Xie, SP, Pirianov, G, Colston, KW (1999) Vitamin D analogues suppress IGF-I signalling and promote apoptosis in breast cancer cells. Eur J Cancer 35: pp. 1717-23 CrossRef
  54. Colston, KW (1998) Growth inhibition of both MCF-7 and Hs578T human breast cancer cell lines by vitamin D analogues is associated with increased expression of insulin-like growth factor binding protein-3. J Mol Endocrinol 20: pp. 157-62 CrossRef
  55. Bezemer, ID (2005) C-peptide, IGF-I, sex-steroid hormones and adiposity: a cross-sectional study in healthy women within the European Prospective Investigation into Cancer and Nutrition (EPIC). Cancer Causes Control 16: pp. 561-72 CrossRef
  56. Lukanova, A (2004) Body mass index, circulating levels of sex-steroid hormones, IGF-I and IGF-binding protein-3: a cross-sectional study in healthy women. Eur J Endocrinol 150: pp. 161-71 CrossRef
  57. Chen, WY (2005) Associations between polymorphisms in the vitamin D receptor and breast cancer risk. Cancer Epidemiol Biomarkers Prev 14: pp. 2335-9 CrossRef
  58. Guy, M (2004) Vitamin D receptor gene polymorphisms and breast cancer risk. Clin Cancer Res 10: pp. 5472-81 CrossRef
  59. Uitterlinden, AG (2004) Vitamin D receptor gene polymorphisms in relation to Vitamin D related disease states. J Steroid Biochem Mol Biol 89–90: pp. 187-93 CrossRef
  60. Buyru, N (2003) Vitamin D receptor gene polymorphisms in breast cancer. Exp Mol Med 35: pp. 550-5 CrossRef
  61. Bretherton-Watt, D (2001) Vitamin D receptor gene polymorphisms are associated with breast cancer risk in a UK Caucasian population. Br J Cancer 85: pp. 171-5 CrossRef
  62. Ingles, SA (2000) Vitamin D receptor genotype and breast cancer in Latinas (United States). Cancer Causes Control 11: pp. 25-30 CrossRef
  63. Curran, JE (1999) Association of A vitamin D receptor polymorphism with sporadic breast cancer development. Int J Cancer 83: pp. 723-6 CrossRef
  64. John, EM (2007) Sun exposure, vitamin D receptor gene polymorphisms, and breast cancer risk in a multiethnic population. Am J Epidemiol 166: pp. 1409-19 CrossRef
  65. McCullough, ML (2007) Vitamin D pathway gene polymorphisms, diet, and risk of postmenopausal breast cancer: a nested case-control study. Breast Cancer Res 9: pp. R9 CrossRef
  66. Guy, M (2003) Approaches to evaluating the association of vitamin D receptor gene polymorphisms with breast cancer risk. Recent Results Cancer Res 164: pp. 43-54 CrossRef
  67. Durrin, LK (1999) Vitamin D receptor 3'-untranslated region polymorphisms: lack of effect on mRNA stability. Biochim Biophys Acta 1453: pp. 311-20 CrossRef
  68. Whitfield, GK (2001) Functionally relevant polymorphisms in the human nuclear vitamin D receptor gene. Mol Cell Endocrinol 177: pp. 145-59 CrossRef
  69. Trabert, B (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: pp. R84 CrossRef
  70. Ruggiero, M (1998) Vitamin D receptor gene polymorphism is associated with metastatic breast cancer. Oncol Res 10: pp. 43-6
  71. Afzal, S (2014) Genetically low vitamin D concentrations and increased mortality: mendelian randomisation analysis in three large cohorts. BMJ 349: pp. g6330 CrossRef
  72. Ahn, J (2010) Genome-wide association study of circulating vitamin D levels. Hum Mol Genet 19: pp. 2739-45 CrossRef
  73. Wang, TJ (2010) Common genetic determinants of vitamin D insufficiency: a genome-wide association study. Lancet 376: pp. 180-8 CrossRef
  74. Abbas, S (2008) The Gc2 allele of the vitamin D binding protein is associated with a decreased postmenopausal breast cancer risk, independent of the vitamin D status. Cancer Epidemiol Biomarkers Prev 17: pp. 1339-43 CrossRef
  75. Reimers LL, et al. Vitamin D-related gene polymorphisms, plasma 25-hydroxyvitamin D, and breast cancer risk. Cancer Causes Control. 2015;26(2):187–203.
  76. Jones, G (2008) Pharmacokinetics of vitamin D toxicity. Am J Clin Nutr 88: pp. 582S-586S
  77. Lappe, JM (2007) Vitamin D and calcium supplementation reduces cancer risk: results of a randomized trial. Am J Clin Nutr 85: pp. 1586-91
  78. Chlebowski, RT (2008) Calcium plus vitamin D supplementation and the risk of breast cancer. J Natl Cancer Inst 100: pp. 1581-91 CrossRef
  79. Wactawski-Wende, J (2006) Calcium plus vitamin D supplementation and the risk of colorectal cancer. N Engl J Med 354: pp. 684-96 CrossRef
  80. Manson, JE (2012) The VITamin D and OmegA-3 TriaL (VITAL): rationale and design of a large randomized controlled trial of vitamin D and marine omega-3 fatty acid supplements for the primary prevention of cancer and cardiovascular disease. Contemp Clin Trials 33: pp. 159-71 CrossRef
  81. Boyd, NF (2005) Mammographic breast density as an intermediate phenotype for breast cancer. Lancet Oncol 6: pp. 798-808 CrossRef
  82. McCormack, VA, Santos Silva, I (2006) Breast density and parenchymal patterns as markers of breast cancer risk: a meta-analysis. Cancer Epidemiol Biomarkers Prev 15: pp. 1159-69 CrossRef
  83. Brisson, J (2007) Synchronized seasonal variations of mammographic breast density and plasma 25-hydroxyvitamin d. Cancer Epidemiol Biomarkers Prev 16: pp. 929-33 CrossRef
  84. Berube, S (2005) Vitamin D and calcium intakes from food or supplements and mammographic breast density. Cancer Epidemiol Biomarkers Prev 14: pp. 1653-9 CrossRef
  85. Diorio, C (2006) Influence of insulin-like growth factors on the strength of the relation of vitamin D and calcium intakes to mammographic breast density. Cancer Res 66: pp. 588-97 CrossRef
  86. Colangelo, LA (2006) A pilot study of vitamin D, calcium, and percent breast density in Hispanic women. Nutr Res 26: pp. 11-15 CrossRef
  87. Crew, KD (2014) Mammographic density and serum 25-hydroxyvitamin D levels. Nutr Metab (Lond) 11: pp. 18 CrossRef
  88. Knight, JA (2006) No association between 25-hydroxyvitamin D and mammographic density. Cancer Epidemiol Biomark Prev 15: pp. 1988-1992 CrossRef
  89. Green, AK (2010) Mammographic density, plasma vitamin D levels and risk of breast cancer in postmenopausal women. Int J Cancer 127: pp. 667-74 CrossRef
  90. Chai, W, Maskarinec, G, Cooney, RV (2010) Serum 25-hydroxyvitamin D levels and mammographic density among premenopausal women in a multiethnic population. Eur J Clin Nutr 64: pp. 652-4 CrossRef
  91. Neuhouser, ML (2010) Serum vitamin D and breast density in breast cancer survivors. Cancer Epidemiol Biomarkers Prev 19: pp. 412-7 CrossRef
  92. Crew KD et al. Safety, feasibility, and biomarker effects of high-dose Vitamin D supplementation among women at high risk for breast cancer. Int J Food Sci Nutr Diet. 2015;S1(100):1–9.