Skip to main content

Advertisement

Log in

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

  • Review article
  • Published:
Cancer Causes & Control Aims and scope Submit manuscript

Abstract

Objective

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.

Methods

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.

Results

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.

Conclusion

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

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.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Cancer Research UK (2008) Commonly diagnosed cancers worldwide

  2. Cancer Research UK (2008) CancerStats report Prostate Cancer—UK, Cancer Research UK

  3. Office for National Statistics (2007) Cancer incidence and mortality in the United Kingdom 2002–2004. Office for National Statistics

  4. Jones G, Strugnell SA, DeLuca HF (1998) Current understanding of the molecular actions of vitamin D. Physiol Rev 78(4):1193–1231

    CAS  PubMed  Google Scholar 

  5. Chen TC, Holick MF (2003) Vitamin D and prostate cancer prevention and treatment. Trends Endocrinol Metabol 14(9):423–430

    Article  CAS  Google Scholar 

  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):1414–1423

    Article  CAS  PubMed  Google Scholar 

  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 108:104–108

    Article  CAS  PubMed  Google Scholar 

  8. Schwartz GG (2005) Vitamin D and the epidemiology of prostate cancer. Semin Dial 18(4):276–289

    Article  PubMed  Google Scholar 

  9. Ali MM, Vaidya V (2007) Vitamin D and cancer. J Cancer Res Ther 3(4):225–230

    Article  CAS  PubMed  Google Scholar 

  10. Peehl DM, Feldman D (2003) The role of vitamin D and retinoids in controlling prostate cancer progression. Endocr Relat Cancer 10(2):131–140

    Article  CAS  PubMed  Google Scholar 

  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):967–971

    Article  CAS  PubMed  Google Scholar 

  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):315–322

    Article  CAS  PubMed  Google Scholar 

  13. Giovannucci E (2005) The epidemiology of vitamin D and cancer incidence and mortality: a review (United States). Cancer Causes Control 16(2):83–95

    Article  PubMed  Google Scholar 

  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):326–331

    CAS  PubMed  Google Scholar 

  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, DC

    Google Scholar 

  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 33:435–445

    Article  CAS  PubMed  Google Scholar 

  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):610–621

    CAS  PubMed  Google Scholar 

  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):1301–1309

    CAS  PubMed  Google Scholar 

  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):2416–2429

    Article  CAS  PubMed  Google Scholar 

  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):3–28

    Google Scholar 

  21. Higgins JP, Thompson SG, Deeks JJ, Altman DG (2003) Measuring inconsistency in meta-analyses. BMJ 327(7414):557–560

    Article  PubMed  Google Scholar 

  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):678–687

    Article  CAS  PubMed  Google Scholar 

  23. Vlajinac HD, Marinkovic JM, Ilic MD, Kocev NI (1997) Diet and prostate cancer: a case-control study. Eur J Cancer 33(1):101–107

    Article  CAS  PubMed  Google Scholar 

  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):591–597

    Article  CAS  PubMed  Google Scholar 

  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):859–867

    Article  CAS  PubMed  Google Scholar 

  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):1118–1123

    Article  PubMed  Google Scholar 

  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):255–265

    Article  PubMed  Google Scholar 

  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):27–33

    Article  CAS  PubMed  Google Scholar 

  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):1147–1154

    CAS  PubMed  Google Scholar 

  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):1259–1269

    Article  PubMed  Google Scholar 

  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):796–804

    Article  CAS  PubMed  Google Scholar 

  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):1929–1933

    Article  CAS  Google Scholar 

  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):719–725

    CAS  Google Scholar 

  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):566–577

    Article  PubMed  Google Scholar 

  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):467–472

    CAS  Google Scholar 

  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):235–239

    Article  CAS  PubMed  Google Scholar 

  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):425–432

    Article  CAS  PubMed  Google Scholar 

  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):533–537

    Article  PubMed  Google Scholar 

  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):586–589

    Article  CAS  Google Scholar 

  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):e103

    Google Scholar 

  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):2784–2786

    Article  CAS  Google Scholar 

  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):1594–1602

    Article  CAS  PubMed  Google Scholar 

  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):1223–1232

    Article  PubMed  Google Scholar 

  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 online

  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):932–936

    Article  CAS  PubMed  Google Scholar 

  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, London

    Google Scholar 

  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, London

  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):2874–2881

    Article  CAS  Google Scholar 

  49. Egger M, Schneider M, Davey SG (1998) Spurious precision? Meta-analysis of observational studies. BMJ 316(7125):140–144

    CAS  PubMed  Google Scholar 

  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):1017–1026

    Article  PubMed  Google Scholar 

  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):2623–2630

    Article  CAS  Google Scholar 

  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):442–447

    CAS  PubMed  Google Scholar 

  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):1195–1202

    PubMed  Google Scholar 

  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):559–566

    Article  CAS  PubMed  Google Scholar 

  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):597–603

    CAS  Google Scholar 

  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):847–852

    Article  CAS  PubMed  Google Scholar 

  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):121–126

    CAS  Google Scholar 

  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):911–923

    Article  CAS  PubMed  Google Scholar 

  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):302–307

    Article  CAS  Google Scholar 

  60. Polek TC, Weigel NL (2002) Vitamin D and prostate cancer. J Androl 23(1):9–17

    CAS  PubMed  Google Scholar 

  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):1768–1777

    Article  CAS  PubMed  Google Scholar 

  62. Calvo MS, Whiting SJ, Barton CN (2005) Vitamin D intake: a global perspective of current status. J Nutr 135(2):310–316

    CAS  PubMed  Google Scholar 

  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):2246–2250

    CAS  PubMed  Google Scholar 

  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 101:278–284

    Article  CAS  PubMed  Google Scholar 

  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):732–744

    Article  PubMed  Google Scholar 

  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 17:148–150

    Google Scholar 

  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):2035–2039

    Article  CAS  PubMed  Google Scholar 

  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):421–441

    Article  PubMed  Google Scholar 

  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):215–226

    Article  CAS  PubMed  Google Scholar 

  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

Download references

Acknowledgments

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.).

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Rebecca Gilbert.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (DOC 33 kb)

10552_2010_9706_MOESM2_ESM.tif

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)

Funnel plots (TIFF 1383 kb)

Rights and permissions

Reprints and permissions

About this article

Cite this article

Gilbert, R., Martin, R.M., Beynon, R. et al. Associations of circulating and dietary vitamin D with prostate cancer risk: a systematic review and dose–response meta-analysis. Cancer Causes Control 22, 319–340 (2011). https://doi.org/10.1007/s10552-010-9706-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10552-010-9706-3

Keywords

Navigation