Cancer Causes & Control

, Volume 22, Issue 3, pp 319–340 | Cite as

Associations of circulating and dietary vitamin D with prostate cancer risk: a systematic review and dose–response meta-analysis

  • Rebecca GilbertEmail author
  • Richard M. Martin
  • Rebecca Beynon
  • Ross Harris
  • Jelena Savovic
  • Luisa Zuccolo
  • Geertruida E. Bekkering
  • William D. Fraser
  • Jonathan A. C. Sterne
  • Chris Metcalfe
Review article



We systematically reviewed and meta-analyzed literature examining associations of vitamin D (dietary intake, circulating 25-hydroxy-vitamin-D (25(OH)D), and 1,25-dihydroxy-vitamin-D (1,25(OH)2D) concentrations) with prostate cancer.


We searched over 24,000 papers from seven electronic databases (to October 2010) for exposures related to vitamin D. We conducted dose–response random-effects meta-analyses pooling the log odds ratio (OR) and 95% confidence intervals (CI) per change in natural units of each exposure. The I2 statistic quantified between-study variation due to heterogeneity.


Twenty-five papers were included. In prospective studies, the OR per 1,000 IU increase in dietary intake was 1.14 (6 studies; CI: 0.99, 1.31; I 2 = 0%) for total prostate cancer and 0.93 (3 studies; 0.63, 1.39; I 2 = 25%) for aggressive prostate cancer. Five case–control studies examined dietary intake, but there was a high degree of inconsistency between studies (I 2 = 49%). The OR per 10 ng/mL increase in 25(OH)D was 1.04 (14 studies; 0.99, 1.10; I 2 = 0%) for total prostate cancer and 0.98 (6 studies; 0.84, 1.15; I 2 = 32%) for aggressive prostate cancer. The OR per 10 pg/mL increase in 1,25(OH)2D was 1.00 (7 studies; 0.87, 1.14; I 2 = 41%) for total prostate cancer and 0.86 (2 studies; 0.72, 1.02; I 2 = 0%) for aggressive prostate cancer.


Published literature provides little evidence to support a major role of vitamin D in preventing prostate cancer or its progression.


Vitamin D Prostatic neoplasms Review Meta-analysis Epidemiology 



We would like to thank Margaret Burke, dedicated information specialist, for carrying out the systematic literature review in the electronic databases. This work was supported by Cancer Research UK (C31211/A10095 to RG, RMM, CM, WDF) and the World Cancer Research Fund (2006/15 to RMM, CM and WDF). The original Expert Report was funded by the World Cancer Research Fund (Davey Smith, G., Sterne, J.A.C., Bain, C. Burke, M., Donovan, J., Ebrahim, S., Egger, M., Emmett, P., Gunnell, D., Hooper, L., Ness, A. and Oliver, S. Systematic review of associations between diet, nutrition, physical activity and bladder, prostate and kidney cancer. World Cancer Research Fund. 1 September 2003–30 June 2006.).

Supplementary material

10552_2010_9706_MOESM1_ESM.doc (34 kb)
Supplementary material 1 (DOC 33 kb)
10552_2010_9706_MOESM2_ESM.tif (77 kb)
Forest plot showing the association of circulating 25-hydroxy-vitamin-D with aggressive prostate cancer (OR per 10 ng/mL increase). Footnotes: Studies ordered by study design and year of publication. Median vitamin D level is estimated, for the control group only where possible, from the available data. If median could not be estimated, the mean in the control group is given (*). P is p-value for heterogeneity. IV = inverse variance, CI = confidence interval (TIFF 76 kb)
10552_2010_9706_MOESM3_ESM.tif (1.4 mb)
Funnel plots (TIFF 1383 kb)


  1. 1.
    Cancer Research UK (2008) Commonly diagnosed cancers worldwideGoogle Scholar
  2. 2.
    Cancer Research UK (2008) CancerStats report Prostate Cancer—UK, Cancer Research UKGoogle Scholar
  3. 3.
    Office for National Statistics (2007) Cancer incidence and mortality in the United Kingdom 2002–2004. Office for National StatisticsGoogle Scholar
  4. 4.
    Jones G, Strugnell SA, DeLuca HF (1998) Current understanding of the molecular actions of vitamin D. Physiol Rev 78(4):1193–1231PubMedGoogle Scholar
  5. 5.
    Chen TC, Holick MF (2003) Vitamin D and prostate cancer prevention and treatment. Trends Endocrinol Metabol 14(9):423–430CrossRefGoogle Scholar
  6. 6.
    Gilbert R, Metcalfe C, Oliver SE et al (2009) Life course sun exposure and risk of prostate cancer: population-based nested case-control study and meta-analysis. Int J Cancer 125(6):1414–1423CrossRefPubMedGoogle Scholar
  7. 7.
    Tuohimaa P, Tenkanen L, Ahonen M et al (2004) Both high and low levels of blood vitamin D are associated with a higher prostate cancer risk: a longitudinal, nested case-control study in the Nordic countries. Int J Cancer 108:104–108CrossRefPubMedGoogle Scholar
  8. 8.
    Schwartz GG (2005) Vitamin D and the epidemiology of prostate cancer. Semin Dial 18(4):276–289CrossRefPubMedGoogle Scholar
  9. 9.
    Ali MM, Vaidya V (2007) Vitamin D and cancer. J Cancer Res Ther 3(4):225–230CrossRefPubMedGoogle Scholar
  10. 10.
    Peehl DM, Feldman D (2003) The role of vitamin D and retinoids in controlling prostate cancer progression. Endocr Relat Cancer 10(2):131–140CrossRefPubMedGoogle Scholar
  11. 11.
    Young MV, Schwartz GG, Wang L et al (2004) The prostate 25-hydroxyvitamin D-1{alpha}-hydroxylase is not influenced by parathyroid hormone and calcium: implications for prostate cancer chemoprevention by vitamin D. Carcinogenesis 25(6):967–971CrossRefPubMedGoogle Scholar
  12. 12.
    Chen TC, Wang L, Whitlatch LW, Flanagan JN, Holick MF (2003) Prostatic 25-hydroxyvitamin D-1alpha-hydroxylase and its implication in prostate cancer. J Cell Biochem 88(2):315–322CrossRefPubMedGoogle Scholar
  13. 13.
    Giovannucci E (2005) The epidemiology of vitamin D and cancer incidence and mortality: a review (United States). Cancer Causes Control 16(2):83–95CrossRefPubMedGoogle Scholar
  14. 14.
    Gross MD (2005) Vitamin D and calcium in the prevention of prostate and colon cancer: new approaches for the identification of needs. J Nutr 135(2):326–331PubMedGoogle Scholar
  15. 15.
    World Cancer Research Fund/American Institute for Cancer Research (2007) Food, nutrition, physical activity, and the prevention of cancer: a global perspective. AICR, Washington, DCGoogle Scholar
  16. 16.
    Yin L, Raum E, Haug U, Arndt V, Brenner H (2009) Meta-analysis of longitudinal studies: serum vitamin D and prostate cancer risk. Cancer Epidemiol 33:435–445CrossRefPubMedGoogle Scholar
  17. 17.
    Chene G, Thompson SG (1996) Methods for summarizing the risk associations of quantitative variables in epidemiologic studies in a consistent form. Am J Epidemiol 144(6):610–621PubMedGoogle Scholar
  18. 18.
    Greenland S, Longnecker MP (1992) Methods for trend estimation from summarized dose-response data, with applications to meta-analysis. Am J Epidemiol 135(11):1301–1309PubMedGoogle Scholar
  19. 19.
    Rowlands MA, Gunnell D, Harris R, Vatten LJ, Holly JM, Martin RM (2009) Circulating insulin-like growth factor peptides and prostate cancer risk: a systematic review and meta-analysis. Int J Cancer 124(10):2416–2429CrossRefPubMedGoogle Scholar
  20. 20.
    Harris RJ, Deeks JJ, Altman DG, Bradburn MJ, Harbord R, Sterne JAC (2008) Metan: fixed- and random-effects meta-analysis. Stata J 8(1):3–28Google Scholar
  21. 21.
    Higgins JP, Thompson SG, Deeks JJ, Altman DG (2003) Measuring inconsistency in meta-analyses. BMJ 327(7414):557–560CrossRefPubMedGoogle Scholar
  22. 22.
    Key TJ, Silcocks PB, Davey GK, Appleby PN, Bishop DT (1997) A case-control study of diet and prostate cancer. Br J Cancer 76(5):678–687CrossRefPubMedGoogle Scholar
  23. 23.
    Vlajinac HD, Marinkovic JM, Ilic MD, Kocev NI (1997) Diet and prostate cancer: a case-control study. Eur J Cancer 33(1):101–107CrossRefPubMedGoogle Scholar
  24. 24.
    Deneo-Pellegrini H, De Stefani E, Ronco A, Mendilaharsu M (1999) Foods, nutrients and prostate cancer: a case-control study in Uruguay. Br J Cancer 80(3–4):591–597CrossRefPubMedGoogle Scholar
  25. 25.
    Chan JM, Pietinen P, Virtanen M et al (2000) Diet and prostate cancer risk in a cohort of smokers, with a specific focus on calcium and phosphorus (Finland). Cancer Causes Control 11(9):859–867CrossRefPubMedGoogle Scholar
  26. 26.
    Berndt SI, Carter HB, Landis PK et al (2002) Calcium intake and prostate cancer risk in a long-term aging study: the baltimore longitudinal study of aging. Urology 60(6):1118–1123CrossRefPubMedGoogle Scholar
  27. 27.
    Platz EA, Leitzmann MF, Hollis BW, Willett WC, Giovannucci E (2004) Plasma 1, 25-dihydroxy- and 25-hydroxyvitamin D and subsequent risk of prostate cancer. Cancer Causes Control 15(3):255–265CrossRefPubMedGoogle Scholar
  28. 28.
    Tavani A, Bertuccio P, Bosetti C et al (2005) Dietary intake of calcium, vitamin D, phosphorus and the risk of prostate cancer. Eur Urol 48(1):27–33CrossRefPubMedGoogle Scholar
  29. 29.
    Tseng M, Breslow RA, Graubard BI, Ziegler RG (2005) Dairy, calcium, and vitamin D intakes and prostate cancer risk in the national health and nutrition examination epidemiologic follow-up study cohort. Am J Clin Nutr 81(5):1147–1154PubMedGoogle Scholar
  30. 30.
    Park SY, Murphy SP, Wilkens LR, Stram DO, Henderson BE, Kolonel LN (2007) Calcium, vitamin D, and dairy product intake and prostate cancer risk: the Multiethnic Cohort Study. Am J Epidemiol 166(11):1259–1269CrossRefPubMedGoogle Scholar
  31. 31.
    Ahn J, Peters U, Albanes D et al (2008) Serum vitamin D concentration and prostate cancer risk: a nested case-control study. J Natl Cancer Inst 100(11):796–804CrossRefPubMedGoogle Scholar
  32. 32.
    Holt SK, Kwon EM, Peters U, Ostrander EA, Stanford JL (2009) Vitamin D pathway gene variants and prostate cancer risk. Cancer Epidemiol Biomark Prev 18(6):1929–1933CrossRefGoogle Scholar
  33. 33.
    Kristal AR, Cohen JH, Qu P, Stanford JL (2002) Associations of energy, fat, calcium, and vitamin D with prostate cancer risk. Cancer Epidemiol Biomark Prev 11(8):719–725Google Scholar
  34. 34.
    Kristal AR, Arnold KB, Neuhouser ML et al (2010) Diet, supplement use, and prostate cancer risk: results from the prostate cancer prevention trial. Am J Epidemiol 172(5):566–577CrossRefPubMedGoogle Scholar
  35. 35.
    Corder EH, Guess HA, Hulka BS et al (1993) Vitamin D and prostate cancer: a prediagnostic study with stored sera. Cancer Epidemiol Biomark Prev 2(5):467–472Google Scholar
  36. 36.
    Braun MM, Helzlsouer KJ, Hollis BW, Comstock GW (1995) Prostate cancer and prediagnostic levels of serum vitamin D metabolites (Maryland, United States). Cancer Causes Control 6(3):235–239CrossRefPubMedGoogle Scholar
  37. 37.
    Nomura AM, Stemmermann GN, Lee J et al (1998) Serum vitamin D metabolite levels and the subsequent development of prostate cancer (Hawaii, United States). Cancer Causes Control 9(4):425–432CrossRefPubMedGoogle Scholar
  38. 38.
    Jacobs ET, Giuliano AR, Martinez ME, Hollis BW, Reid ME, Marshall JR (2004) Plasma levels of 25-hydroxyvitamin D, 1, 25-dihydroxyvitamin D and the risk of prostate cancer. J Steroid Biochem Mol Biol 89–90(1–5):533–537CrossRefPubMedGoogle Scholar
  39. 39.
    Baron JA, Beach M, Wallace K et al (2005) Risk of prostate cancer in a randomized clinical trial of calcium supplementation. Cancer Epidemiol Biomark Prev 14(3):586–589CrossRefGoogle Scholar
  40. 40.
    Li H, Stampfer MJ, Hollis JB et al (2007) A prospective study of plasma vitamin D metabolites, vitamin D receptor polymorphisms, and prostate cancer. PLoS Med Public Libr Sci 4(3):e103Google Scholar
  41. 41.
    Faupel-Badger JM, Diaw L, Albanes D, Virtamo J, Woodson K, Tangrea JA (2007) Lack of association between serum levels of 25-Hydroxyvitamin D and the subsequent risk of prostate cancer in finnish men. Cancer Epidemiol Biomark Prev 16(12):2784–2786CrossRefGoogle Scholar
  42. 42.
    Freedman DM, Looker AC, Chang SC, Graubard BI (2007) Prospective study of serum vitamin D and cancer mortality in the United States. J Natl Cancer Inst 99(21):1594–1602CrossRefPubMedGoogle Scholar
  43. 43.
    Travis RC, Crowe FL, Allen NE et al (2009) Serum vitamin D and risk of prostate cancer in a case-control analysis nested within the European prospective investigation into cancer and nutrition (EPIC). Am J Epidemiol 169(10):1223–1232CrossRefPubMedGoogle Scholar
  44. 44.
    Barnett CM, Nielson CM, Shannon J et al. (2010) Serum 25-OH vitamin D levels and risk of developing prostate cancer in older men. Cancer Causes and Control onlineGoogle Scholar
  45. 45.
    Park SY, Cooney RV, Wilkens LR, Murphy SP, Henderson BE, Kolonel LN (2010) Plasma 25-hydroxyvitamin D and prostate cancer risk: the multiethnic cohort. Eur J Cancer 46(5):932–936CrossRefPubMedGoogle Scholar
  46. 46.
    Bates B, Lennox A, Swan G (2010) National diet and nutrition survey: headline results from year 1 of the rolling programme (2008/2009). Food Standards Agency, Department of Health, LondonGoogle Scholar
  47. 47.
    Ruston D, Henderson L, Gregory J et al. (2004) The national diet and nutrition survey: adults aged 19–64 years. Volume 4: nutritional status (anthropometry and blood analytes), blood pressure and physical activity. TSO, LondonGoogle Scholar
  48. 48.
    Chen L, Davey SG, Evans DM et al (2009) Genetic variants in the vitamin d receptor are associated with advanced prostate cancer at diagnosis: findings from the prostate testing for cancer and treatment study and a systematic review. Cancer Epidemiol Biomark Prev 18(11):2874–2881CrossRefGoogle Scholar
  49. 49.
    Egger M, Schneider M, Davey SG (1998) Spurious precision? Meta-analysis of observational studies. BMJ 316(7125):140–144PubMedGoogle Scholar
  50. 50.
    Bekkering GE, Harris RJ, Thomas S et al (2008) How much of the data published in observational studies of the association between diet and prostate or bladder cancer is usable for meta-analysis? Am J Epidemiol 167(9):1017–1026CrossRefPubMedGoogle Scholar
  51. 51.
    Ahn J, Albanes D, Peters U et al (2007) Dairy products, calcium intake, and risk of prostate cancer in the prostate, lung, colorectal, and ovarian cancer screening trial. Cancer Epidemiol Biomark Prev 16(12):2623–2630CrossRefGoogle Scholar
  52. 52.
    Giovannucci E, Rimm EB, Wolk A et al (1998) Calcium and fructose intake in relation to risk of prostate cancer. Cancer Res 58(3):442–447PubMedGoogle Scholar
  53. 53.
    Galic J, Simunovic D (2008) Prostate disease prevalence with epidemiological and hormonal analysis in randomly selected male population in Croatia. Coll Antropol 32(4):1195–1202PubMedGoogle Scholar
  54. 54.
    Chan JM, Giovannucci E, Andersson SO, Yuen J, Adami HO, Wolk A (1998) Dairy products, calcium, phosphorous, vitamin D, and risk of prostate cancer (Sweden). Cancer Causes Control 9(6):559–566CrossRefPubMedGoogle Scholar
  55. 55.
    Rodriguez C, McCullough ML, Mondul AM et al (2003) Calcium, dairy products, and risk of prostate cancer in a prospective cohort of United States men. Cancer Epidemiol Biomark Prev 12(7):597–603Google Scholar
  56. 56.
    Ahonen MH, Tenkanen L, Teppo L, Hakama M, Tuohimaa P (2000) Prostate cancer risk and prediagnostic serum 25-hydroxyvitamin D levels (Finland). Cancer Causes Control 11(9):847–852CrossRefPubMedGoogle Scholar
  57. 57.
    Gann PH, Ma J, Hennekens CH, Hollis BW, Haddad JG, Stampfer MJ (1996) Circulating vitamin D metabolites in relation to subsequent development of prostate cancer. Cancer Epidemiol Biomark Prev 5(2):121–126Google Scholar
  58. 58.
    Mikhak B, Hunter DJ, Spiegelman D, Platz EA, Hollis BW, Giovannucci E (2007) Vitamin D receptor (VDR) gene polymorphisms and haplotypes, interactions with plasma 25-hydroxyvitamin D and 1, 25-dihydroxyvitamin D, and prostate cancer risk. Prostate 67(9):911–923CrossRefPubMedGoogle Scholar
  59. 59.
    Tuohimaa P, Tenkanen L, Syvala H et al (2007) Interaction of factors related to the metabolic syndrome and vitamin D on risk of prostate cancer. Cancer Epidemiol Biomark Prev 16(2):302–307CrossRefGoogle Scholar
  60. 60.
    Polek TC, Weigel NL (2002) Vitamin D and prostate cancer. J Androl 23(1):9–17PubMedGoogle Scholar
  61. 61.
    Gao X, LaValley MP, Tucker KL (2005) Prospective studies of dairy product and calcium intakes and prostate cancer risk: a meta-analysis. J Natl Cancer Inst 97(23):1768–1777CrossRefPubMedGoogle Scholar
  62. 62.
    Calvo MS, Whiting SJ, Barton CN (2005) Vitamin D intake: a global perspective of current status. J Nutr 135(2):310–316PubMedGoogle Scholar
  63. 63.
    Rohde CM, Manatt M, Clagett-Dame M, DeLuca HF (1999) Vitamin A antagonizes the action of vitamin D in rats. J Nutr 129(12):2246–2250PubMedGoogle Scholar
  64. 64.
    Bodnar LM, Catov JM, Wisner KL, Klebanoff MA (2009) Racial and seasonal differences in 25-hydroxyvitamin D detected in maternal sera frozen for over 40 years. Br J Nutr 101:278–284CrossRefPubMedGoogle Scholar
  65. 65.
    Ross LE, Coates RJ, Breen N, Uhler RJ, Potosky AL, Blackman D (2004) Prostate-specific antigen test use reported in the 2000 national health interview survey. Prev Med 38(6):732–744CrossRefPubMedGoogle Scholar
  66. 66.
    Weinrich S, Ellison G, Weinrich M, Ross KS, Reis-Starr C (2002) Low sun exposure and elevated serum prostate specific antigen in African American and Caucasian men. Am J Health Stud 17:148–150Google Scholar
  67. 67.
    Gross C, Stamey T, Hancock S, Feldman D (1998) Treatment of early recurrent prostate cancer with 1, 25-dihydroxyvitamin D3 (calcitriol). J Urol 159(6):2035–2039CrossRefPubMedGoogle Scholar
  68. 68.
    Huncharek M, Muscat J, 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):421–441CrossRefPubMedGoogle Scholar
  69. 69.
    Gupta D, Lammersfeld CA, Trukova K, Lis CG (2009) Vitamin D and prostate cancer risk: a review of the epidemiological literature. Prostate Cancer Prostatic Dis 12(3):215–226CrossRefPubMedGoogle Scholar
  70. 70.
    Gandini S, Boniol M, Haukka J et al. (2010) Meta-analysis of observational studies of serum 25-hydroxyvitamin D levels and colorectal, breast and prostate cancer and colorectal adenoma. Int J Cancer. doi: 10.1002/ijc.25439

Copyright information

© Springer Science+Business Media B.V. 2010

Authors and Affiliations

  • Rebecca Gilbert
    • 1
    Email author
  • Richard M. Martin
    • 1
  • Rebecca Beynon
    • 1
  • Ross Harris
    • 2
  • Jelena Savovic
    • 1
  • Luisa Zuccolo
    • 1
  • Geertruida E. Bekkering
    • 3
    • 4
  • William D. Fraser
    • 5
  • Jonathan A. C. Sterne
    • 1
  • Chris Metcalfe
    • 1
  1. 1.School of Social and Community MedicineUniversity of BristolBristolUK
  2. 2.Statistics UnitHealth Protection Agency, Centre for InfectionsLondonUK
  3. 3.Department of General PracticeKatholieke Universiteit LeuvenLeuvenBelgium
  4. 4.BeSyRe Bekkering Systematic ReviewsGeelBelgium
  5. 5.Unit of Clinical ChemistrySchool of Clinical Sciences, University of LiverpoolLiverpoolUK

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