Skip to main content

Advertisement

Log in

Meta-analysis of vitamin D, calcium and the prevention of breast cancer

  • Epidemiology
  • Published:
Breast Cancer Research and Treatment Aims and scope Submit manuscript

Abstract

Vitamin D and calcium intake have been suggested to have protective effects against breast cancer; however, the data have been inconclusive. The present meta-analysis examined the overall effects of vitamin D intake, circulating 25(OH)D and 1α,25(OH)2D levels, and calcium intake on breast cancer risk. Data from 11 studies on vitamin D intake, 7 studies on circulating 25(OH)D levels, 3 studies of circulating 1α,25(OH)2D levels, and 15 studies on calcium intake and breast cancer risk were included in this analysis. From the meta-analysis, there was a significant inverse relationship between vitamin D intake and breast cancer risk, with an overall relative risk (RR) of high versus low vitamin D intake for breast cancer of 0.91 (95% CI = 0.85–0.97). The highest quantile of circulating 25(OH)D was found to be associated with a 45% (OR = 0.55, 95% CI = 0.38–0.80) decrease in breast cancer when compared with the lowest quantile. No significant association for the circulating 1α,25(OH)2D level and breast cancer was found (OR = 0.99, 95% CI = 0.68–1.44). For calcium, a 19% (RR = 0.81, 95% CI = 0.72–0.90) decrease in breast cancer risk was found for those with highest quantile of calcium intake compared to the lowest quantile. These results provide strong evidence that vitamin D and calcium have a chemopreventive effect against breast cancer.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  1. Garland CF, Garland FC, Gorham ED et al (2006) The role of vitamin D in cancer prevention. Am J Public Health 96:252–261. doi:10.2105/AJPH.2004.045260

    Article  PubMed  Google Scholar 

  2. Chen TC, Holick MF (2003) Vitamin D and prostate cancer prevention and treatment. Trends Endocrinol Metab 14:423–430. doi:10.1016/j.tem.2003.09.004

    Article  CAS  PubMed  Google Scholar 

  3. Cui Y, Rohan TE (2006) Vitamin D, calcium, and breast cancer risk: a review. Cancer Epidemiol Biomarkers Prev 15:1427–1437

    Article  CAS  PubMed  Google Scholar 

  4. Wei MY, Garland CF, Gorham ED, Mohr SB, Giovannucci E (2008) Vitamin D and prevention of colorectal adenoma: a meta-analysis. Cancer Epidemiol Biomarkers Prev 17:2958–2969. doi:10.1158/1055-9965.EPI-08-0402

    Article  CAS  PubMed  Google Scholar 

  5. Bertone-Johnson ER (2009) Vitamin D and breast cancer. Ann Epidemiol 19:462–467. doi:10.1016/j.annepidem.2009.01.003

    Article  PubMed  Google Scholar 

  6. Garland FC, Garland CF, Gorham ED, Young JF (1990) Geographic variation in breast cancer mortality in the United States: a hypothesis involving exposure to solar radiation. Prev Med 19:614–622

    Article  CAS  PubMed  Google Scholar 

  7. Gorham ED, Garland FC, Garland CF (1990) Sunlight and breast cancer incidence in the USSR. Int J Epidemiol 19:820–824

    Article  CAS  PubMed  Google Scholar 

  8. Grant WB (2002) An ecologic study of dietary and solar ultraviolet-B links to breast carcinoma mortality rates. Cancer 94:272–281. doi:10.1002/cncr.10196

    Article  PubMed  Google Scholar 

  9. Deeb KK, Trump DL, Johnson CS (2007) Vitamin D signalling pathways in cancer: potential for anticancer therapeutics. Nat Rev Cancer 7:684–700. doi:10.1038/nrc2196

    Article  CAS  PubMed  Google Scholar 

  10. Tang C, Chen N, Wu M, Yuan H, Du Y (2009) Fok1 polymorphism of vitamin D receptor gene contributes to breast cancer susceptibility: a meta-analysis. Breast Cancer Res Treat 117:391–399. doi:10.1007/s10549-008-0262-4

    Article  CAS  PubMed  Google Scholar 

  11. Raimondi S, Johansson H, Maisonneuve P, Gandini S (2009) Review and meta-analysis on vitamin D receptor polymorphisms and cancer risk. Carcinogenesis 30:1170–1180. doi:10.1093/carcin/bgp103

    Article  CAS  PubMed  Google Scholar 

  12. Mathiasen IS, Sergeev IN, Bastholm L, Elling F, Norman AW, Jaattela M (2002) Calcium and calpain as key mediators of apoptosis-like death induced by vitamin D compounds in breast cancer cells. J Biol Chem 277:30738–30745

    Article  CAS  PubMed  Google Scholar 

  13. Sergeev IN (2004) Calcium as a mediator of 1,25-dihydroxyvitamin D3-induced apoptosis. J Steroid Biochem Mol Biol 89–90:419–425. doi:10.1016/j.jsbmb.2004.03.010

    Article  PubMed  Google Scholar 

  14. Ishimi Y, Russell J, Sherwood LM (1990) Regulation by calcium and 1,25-(OH)2D3 of cell proliferation and function of bovine parathyroid cells in culture. J Bone Miner Res 5:755–760

    Article  CAS  PubMed  Google Scholar 

  15. Chopra DP, Sullivan JK, Reece-Kooyer S (1990) Regulation by calcium of proliferation and morphology of normal human tracheobronchial epithelial cell cultures. J Cell Sci 96:509–517

    CAS  PubMed  Google Scholar 

  16. Whitfield JF, Boynton AL, MacManus JP, Sikorska M, Tsang BK (1979) The regulation of cell proliferation by calcium and cyclic AMP. Mol Cell Biochem 27:155–179. doi:10.1007/BF00215364

    Article  CAS  PubMed  Google Scholar 

  17. Xue L, Lipkin M, Newmark H, Wang J (1999) Influence of dietary calcium and vitamin D on diet-induced epithelial cell hyperproliferation in mice. J Natl Cancer Inst 91:176–181. doi:10.1093/jnci/91.2.176

    Article  CAS  PubMed  Google Scholar 

  18. Jacobson EA, James KA, Newmark HL, Carroll KK (1989) Effects of dietary fat, calcium, and vitamin D on growth and mammary tumorigenesis induced by 7,12-dimethylbenz(a)anthracene in female Sprague-Dawley rats. Cancer Res 49:6300–6303

    CAS  PubMed  Google Scholar 

  19. Kesse-Guyot E, Bertrais S, Duperray B et al (2007) Dairy products, calcium and the risk of breast cancer: results of the French SU.VI.MAX prospective study. Ann Nutr Metab 51:139–145. doi:10.1159/000103274

    Article  CAS  PubMed  Google Scholar 

  20. Knekt P, Jarvinen R, Seppanen R, Pukkala E, Aromaa A (1996) Intake of dairy products and the risk of breast cancer. Br J Cancer 73:687–691

    CAS  PubMed  Google Scholar 

  21. Landa MC, Frago N, Tres A (1994) Diet and the risk of breast cancer in Spain. Eur J Cancer Prev 3:313–320

    Article  CAS  PubMed  Google Scholar 

  22. 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 59:54–61. doi:10.1080/01635580701390223

    CAS  PubMed  Google Scholar 

  23. Shin MH, Holmes MD, Hankinson SE, Wu K, Colditz GA, Willett WC (2002) Intake of dairy products, calcium, and vitamin D and risk of breast cancer. J Natl Cancer Inst 94:1301–1311. doi:10.1093/jnci/94.17.1301

    CAS  PubMed  Google Scholar 

  24. Egger M, Davey Smith G, Schneider M, Minder C (1997) Bias in meta-analysis detected by a simple, graphical test. BMJ 315:629–634

    CAS  PubMed  Google Scholar 

  25. Peters JL, Sutton AJ, Jones DR, Abrams KR, Rushton L (2007) Performance of the trim and fill method in the presence of publication bias and between-study heterogeneity. Stat Med 26:4544–4562. doi:10.1002/sim.2889

    Article  PubMed  Google Scholar 

  26. Duval S, Tweedie R (2000) Trim and fill: a simple funnel-plot-based method of testing and adjusting for publication bias in meta-analysis. Biometrics 56:455–463. doi:10.1111/j.0006-341X.2000.00455.x

    Article  CAS  PubMed  Google Scholar 

  27. Simard A, Vobecky J, Vobecky JS (1991) Vitamin D deficiency and cancer of the breast: an unprovocative ecological hypothesis. Can J Public Health 82:300–303

    CAS  PubMed  Google Scholar 

  28. Potischman N, Swanson CA, Coates RJ et al (1999) Intake of food groups and associated micronutrients in relation to risk of early-stage breast cancer. Int J Cancer 82:315–321. doi:10.1002/(SICI)1097-0215(19990730)82:3<315:AID-IJC1>3.0.CO;2-N

    Article  CAS  PubMed  Google Scholar 

  29. Levi F, Pasche C, Lucchini F, La Vecchia C (2001) Dietary intake of selected micronutrients and breast-cancer risk. Int J Cancer 91:260–263. doi:10.1002/1097-0215(200002)9999:9999<:AID-IJC1041>3.0.CO;2-#

    Article  CAS  PubMed  Google Scholar 

  30. Rossi M, McLaughlin JK, Lagiou P et al (2009) Vitamin D intake and breast cancer risk: a case-control study in Italy. Ann Oncol 20:374–378. doi:10.1093/annonc/mdn550

    Article  CAS  PubMed  Google Scholar 

  31. John EM, Schwartz GG, Dreon DM, Koo J (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 8:399–406

    CAS  PubMed  Google Scholar 

  32. Frazier AL, Li L, Cho E, Willett WC, Colditz GA (2004) Adolescent diet and risk of breast cancer. Cancer Causes Control 15:73–82. doi:10.1023/B:CACO.0000016617.57120.df

    Article  PubMed  Google Scholar 

  33. McCullough ML, Rodriguez C, Diver WR 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 14:2898–2904

    Article  CAS  PubMed  Google Scholar 

  34. Lin J, Manson JE, Lee IM, Cook NR, Buring JE, Zhang SM (2007) Intakes of calcium and vitamin D and breast cancer risk in women. Arch Intern Med 167:1050–1059

    Article  CAS  PubMed  Google Scholar 

  35. 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 18:775–782. doi:10.1007/s10552-007-9020-x

    Article  PubMed  Google Scholar 

  36. Lowe LC, Guy M, Mansi JL 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 41:1164–1169. doi:10.1016/j.ejca.2005.01.017

    Article  CAS  PubMed  Google Scholar 

  37. Abbas S, Linseisen J, Slanger T et al (2008) Serum 25-hydroxyvitamin D and risk of post-menopausal breast cancer—results of a large case-control study. Carcinogenesis 29:93–99. doi:10.1093/carcin/bgm240

    Article  CAS  PubMed  Google Scholar 

  38. 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 124:250–255. doi:10.1002/ijc.23904

    Article  CAS  PubMed  Google Scholar 

  39. Crew KD, Gammon MD, Steck SE et al (2009) Association between plasma 25-hydroxyvitamin D and breast cancer risk. Cancer Prev Res 2:598–604. doi:10.1158/1940-6207.CAPR-08-0138

    Article  Google Scholar 

  40. Bertone-Johnson ER, Chen WY, Holick MF et al (2005) Plasma 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D and risk of breast cancer. Cancer Epidemiol Biomarkers Prev 14:1991–1997

    Article  CAS  PubMed  Google Scholar 

  41. Chlebowski RT, Johnson KC, Kooperberg C et al (2008) Calcium plus vitamin D supplementation and the risk of breast cancer. J Natl Cancer Inst 100:1581–1591. doi:10.1093/jnci/djn360

    Article  CAS  PubMed  Google Scholar 

  42. Freedman DM, Chang SC, Falk RT 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 17:889–894. doi:10.1158/1055-9965.EPI-07-2594

    Article  CAS  PubMed  Google Scholar 

  43. Hiatt RA, Krieger N, Lobaugh B, Drezner MK, Vogelman JH, Orentreich N (1998) Prediagnostic serum vitamin D and breast cancer. J Natl Cancer Inst 90:461–463

    Article  CAS  PubMed  Google Scholar 

  44. Janowsky EC, Lester GE, Weinberg CR et al (1999) Association between low levels of 1,25-dihydroxyvitamin D and breast cancer risk. Public Health Nutr 2:283–291. doi:10.1017/S1368980099000385

    Article  CAS  PubMed  Google Scholar 

  45. Larsson SC, Bergkvist L, Wolk A (2009) Long-term dietary calcium intake and breast cancer risk in a prospective cohort of women. Am J Clin Nutr 89:277–282. doi:10.3945/ajcn.2008.26704

    Article  CAS  PubMed  Google Scholar 

  46. Boyapati SM, Shu XO, Jin F et al (2003) Dietary calcium intake and breast cancer risk among Chinese women in Shanghai. Nutr Cancer 46:38–43. doi:10.1207/S15327914NC4601_05

    Article  CAS  PubMed  Google Scholar 

  47. Adzersen KH, Jess P, Freivogel KW, Gerhard I, Bastert G (2003) Raw and cooked vegetables, fruits, selected micronutrients, and breast cancer risk: a case-control study in Germany. Nutr Cancer 46:131–137. doi:10.1207/S15327914NC4602_05

    Article  CAS  PubMed  Google Scholar 

  48. Negri E, La Vecchia C, Franceschi S et al (1996) Intake of selected micronutrients and the risk of breast cancer. Int J Cancer 65:140–144

    Article  CAS  PubMed  Google Scholar 

  49. Zaridze D, Lifanova Y, Maximovitch D, Day NE, Duffy SW (1991) Diet, alcohol consumption and reproductive factors in a case-control study of breast cancer in Moscow. Int J Cancer 48:493–501

    Article  CAS  PubMed  Google Scholar 

  50. Katsouyanni K, Willett W, Trichopoulos D et al (1988) Risk of breast cancer among Greek women in relation to nutrient intake. Cancer 61:181–185

    Article  CAS  PubMed  Google Scholar 

  51. Gissel T, Rejnmark L, Mosekilde L, Vestergaard P (2008) Intake of vitamin D and risk of breast cancer—a meta-analysis. J Steroid Biochem Mol Biol 111:195–199. doi:10.1016/j.jsbmb.2008.06.002

    Article  CAS  PubMed  Google Scholar 

  52. Garland CF, Gorham ED, Mohr SB et al (2007) Vitamin D and prevention of breast cancer: pooled analysis. J Steroid Biochem Mol Biol 103:708–711. doi:10.1016/j.jsbmb.2006.12.007

    Article  CAS  PubMed  Google Scholar 

  53. Pérez-López FR, Chedraui P, Haya J (2009) Vitamin D acquisition and breast cancer risk. Reprod Sci 16:7–19. doi:10.1177/1933719108327595

    Article  PubMed  Google Scholar 

  54. Brisson J, Berube S, Diorio C, Sinotte M, Pollak M, Masse B (2007) Synchronized seasonal variations of mammographic breast density and plasma 25-hydroxyvitamin D. Cancer Epidemiol Biomarkers Prev 16:929–933. doi:10.1158/1055-9965.EPI-06-0746

    Article  CAS  PubMed  Google Scholar 

  55. Berube S, Diorio C, Masse B et al (2005) Vitamin D and calcium intakes from food or supplements and mammographic breast density. Cancer Epidemiol Biomarkers Prev 14:1653–1659

    Article  CAS  PubMed  Google Scholar 

  56. Rohan TE, Negassa A, Chlebowski RT et al (2009) A randomized controlled trial of calcium plus vitamin D supplementation and risk of benign proliferative breast disease. Breast Cancer Res Treat 116:339–350. doi:10.1007/s10549-008-0213-0

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

This study was supported by a grant from One Hundred Talents Program of the Chinese Academy of Sciences, a grant from the National Nature Science Foundation (30870513), a grant (2007CB947100) from the Ministry of Science and Technology of China, a grant (08391910800) from the Science and Technology Commission of Shanghai Municipality and the Food Safety Research Center and Key Laboratory of Nutrition and Metabolism. We thank Dr. Elizabeth R. Rayburn for assistance in editing this manuscript.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Hui Wang.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary Table 1

Studies included in the comparison of the high versus low quantiles of vitamin D intake and breast cancer risk. (XLSM 13 kb)

Supplementary material 2 (XLSM 15 kb)

Supplementary material 3 (XLSM 14 kb)

Supplementary Table 2

Studies included for meta-analysis of circulating 25(OH)D levels and breast cancer risk. (XLSM 15 kb)

Supplementary Table 3

Studies included for meta-analysis of circulating 1α,25(OH)2D levels and breast cancer risk. (XLSM 12 kb)

Supplementary Table 4

Included studies of high versus low quantiles of calcium intake and breast cancer risk. (XLSM 14 kb)

Supplementary material 7 (XLSM 15 kb)

Supplementary material 8 (XLSM 16 kb)

Supplementary material 9 (XLSM 14 kb)

Rights and permissions

Reprints and permissions

About this article

Cite this article

Chen, P., Hu, P., Xie, D. et al. Meta-analysis of vitamin D, calcium and the prevention of breast cancer. Breast Cancer Res Treat 121, 469–477 (2010). https://doi.org/10.1007/s10549-009-0593-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10549-009-0593-9

Keywords

Navigation