Tumor Biology

, Volume 36, Issue 3, pp 1567–1572 | Cite as

Impact of serum vitamin D level on risk of bladder cancer: a systemic review and meta-analysis

  • Yong Liao
  • Jian-Lin Huang
  • Ming-Xing Qiu
  • Zhi-Wei Ma
Research Article


Vitamin D has important biological functions including modulation of the immune system and anti-cancer effects. There was no conclusive finding of the impact of serum vitamin D level on bladder cancer risk. A systemic review and meta-analysis was performed to assess the impact of serum 25-hydroxyvitamin D level on bladder cancer risk. The pooled relative risk (RR) with 95 % confidence interval (95%CI) was used to assess the impact of serum 25-hydroxyvitamin D level on bladder cancer risk. A total of 89,610 participants and 2238 bladder cancer cases were finally included into the meta-analysis. There was no obvious heterogeneity among those included studies (I 2 = 0 %). Meta-analysis total included studies which showed that a high serum 25-hydroxyvitamin D level could obviously decrease risk of bladder cancer (RR = 0.75, 95%CI 0.65–0.87, P < 0.001). In addition, the pooled RRs were not significantly changed by excluding any single study. The findings from the meta-analysis suggest an obvious protective effect of vitamin D against bladder cancer. Individuals with higher serum 25-hydroxyvitamin D levels suffer from less risk of subsequent bladder cancer.


Bladder cancer Vitamin D Risk Meta-analysis 


Conflicts of interest



  1. 1.
    Apolo AB, Hoffman V, Kaag MG, Latini DM, Lee CT, Rosenberg JE, et al. Summary of the 8th annual bladder cancer think tank: collaborating to move research forward. Urol Oncol. 2014.Google Scholar
  2. 2.
    Jemal A, Siegel R, Xu J, Ward E. Cancer statistics, 2010. CA Cancer J Clin. 2010;60:277–300.CrossRefPubMedGoogle Scholar
  3. 3.
    Keimling M, Behrens G, Schmid D, Jochem C, Leitzmann MF. The association between physical activity and bladder cancer: systematic review and meta-analysis. Br J Cancer. 2014;110:1862–70.CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    Mohr SB, Garland CF, Gorham ED, Grant WB, Garland FC. Ultraviolet b irradiance and incidence rates of bladder cancer in 174 countries. Am J Prev Med. 2010;38:296–302.CrossRefPubMedGoogle Scholar
  5. 5.
    Kaufman DS, Shipley WU, Feldman AS. Bladder cancer. Lancet. 2009;374:239–49.CrossRefPubMedGoogle Scholar
  6. 6.
    Albert PJ, Proal AD, Marshall TG. Vitamin D: the alternative hypothesis. Autoimmun Rev. 2009;8:639–44.CrossRefPubMedGoogle Scholar
  7. 7.
    Dixon KM, Mason RS. Vitamin D. Int J Biochem Cell Biol. 2009;41:982–5.CrossRefPubMedGoogle Scholar
  8. 8.
    Plum LA, DeLuca HF. Vitamin D, disease and therapeutic opportunities. Nat Rev Drug Discov. 2010;9:941–55.CrossRefPubMedGoogle Scholar
  9. 9.
    Mora JR, Iwata M, von Andrian UH. Vitamin effects on the immune system: vitamins A and D take centre stage. Nat Rev Immunol. 2008;8:685–98.CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Bikle D. Nonclassic actions of vitamin D. J Clin Endocrinol Metab. 2009;94:26–34.CrossRefPubMedGoogle Scholar
  11. 11.
    Bischoff-Ferrari HA. Optimal serum 25-hydroxyvitamin D levels for multiple health outcomes. Adv Exp Med Biol. 2014;810:500–25.PubMedGoogle Scholar
  12. 12.
    Ordonez Mena JM, Brenner H. Vitamin D and cancer: an overview on epidemiological studies. Adv Exp Med Biol. 2014;810:17–32.PubMedGoogle Scholar
  13. 13.
    Lee JE, Li H, Chan AT, et al. Circulating levels of vitamin D and colon and rectal cancer: the physicians’ health study and a meta-analysis of prospective studies. Cancer Prev Res (Phila). 2011;4:735–43.CrossRefGoogle Scholar
  14. 14.
    Ordonez-Mena JM, Schottker B, Haug U, et al. Serum 25-hydroxyvitamin D and cancer risk in older adults: results from a large German prospective cohort study. Cancer Epidemiol Biomarkers Prev. 2013;22:905–16.CrossRefPubMedGoogle Scholar
  15. 15.
    Kim Y, Je Y. Vitamin D intake, blood 25(OH)D levels, and breast cancer risk or mortality: a meta-analysis. Br J Cancer. 2014;110:2772–84.CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    Giovannucci E, Liu Y, Rimm EB, et al. Prospective study of predictors of vitamin D status and cancer incidence and mortality in men. J Natl Cancer Inst. 2006;98:451–9.CrossRefPubMedGoogle Scholar
  17. 17.
    Amaral AF, Mendez-Pertuz M, Munoz A, et al. Plasma 25-hydroxyvitamin D(3) and bladder cancer risk according to tumor stage and FGFR3 status: a mechanism-based epidemiological study. J Natl Cancer Inst. 2012;104:1897–904.CrossRefPubMedPubMedCentralGoogle Scholar
  18. 18.
    Afzal S, Bojesen SE, Nordestgaard BG. Low plasma 25-hydroxyvitamin D and risk of tobacco-related cancer. Clin Chem. 2013;59:771–80.CrossRefPubMedGoogle Scholar
  19. 19.
    Mondul AM, Weinstein SJ, Horst RL, Purdue M, Albanes D. Serum vitamin D and risk of bladder cancer in the prostate, lung, colorectal, and ovarian (PLCO) cancer screening trial. Cancer Epidemiol Biomarkers Prev. 2012;21:1222–5.CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    Mondul AM, Weinstein SJ, Virtamo J, Albanes D. Influence of vitamin D binding protein on the association between circulating vitamin D and risk of bladder cancer. Br J Cancer. 2012;107:1589–94.CrossRefPubMedPubMedCentralGoogle Scholar
  21. 21.
    Higgins JP, Thompson SG, Deeks JJ, Altman DG. Measuring inconsistency in meta-analyses. BMJ. 2003;327:557–60.CrossRefPubMedPubMedCentralGoogle Scholar
  22. 22.
    DerSimonian R, Laird N. Meta-analysis in clinical trials. Control Clin Trials. 1986;7:177–88.CrossRefPubMedGoogle Scholar
  23. 23.
    Mantel N, Haenszel W. Statistical aspects of the analysis of data from retrospective studies of disease. J Natl Cancer Inst. 1959;22:719–48.PubMedGoogle Scholar
  24. 24.
    Egger M, Davey Smith G, Schneider M, Minder C. Bias in meta-analysis detected by a simple, graphical test. BMJ. 1997;315:629–34.CrossRefPubMedPubMedCentralGoogle Scholar
  25. 25.
    Peters JL, Sutton AJ, Jones DR, Abrams KR, Rushton L. Performance of the trim and fill method in the presence of publication bias and between-study heterogeneity. Stat Med. 2007;26:4544–62.CrossRefPubMedGoogle Scholar
  26. 26.
    Mondul AM, Weinstein SJ, Mannisto S, et al. Serum vitamin D and risk of bladder cancer. Cancer Res. 2010;70:9218–23.CrossRefPubMedPubMedCentralGoogle Scholar
  27. 27.
    Pommergaard HC, Burcharth J, Rosenberg J, Raskov H. Oral chemoprevention with acetyl salicylic acid, vitamin D and calcium reduces the risk of tobacco carcinogen-induced bladder tumors in mice. Cancer Invest. 2013;31:490–3.CrossRefPubMedGoogle Scholar
  28. 28.
    Krishnan AV, Feldman D. Mechanisms of the anti-cancer and anti-inflammatory actions of vitamin D. Annu Rev Pharmacol Toxicol. 2011;51:311–36.CrossRefPubMedGoogle Scholar
  29. 29.
    Chen P, Li M, Gu X, et al. Higher blood 25(OH)D level may reduce the breast cancer risk: evidence from a Chinese population based case–control study and meta-analysis of the observational studies. PLoS One. 2013;8:e49312.CrossRefPubMedPubMedCentralGoogle Scholar
  30. 30.
    Chung M, Lee J, Terasawa T, Lau J, Trikalinos TA. Vitamin D with or without calcium supplementation for prevention of cancer and fractures: an updated meta-analysis for the U.S. Preventive Services Task Force. Ann Intern Med. 2011;155:827–38.CrossRefPubMedGoogle Scholar
  31. 31.
    Bolland MJ, Grey A, Gamble GD, Reid IR. The effect of vitamin D supplementation on skeletal, vascular, or cancer outcomes: a trial sequential meta-analysis. Lancet Diabetes Endocrinol. 2014;2:307–20.CrossRefPubMedGoogle Scholar

Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2014

Authors and Affiliations

  • Yong Liao
    • 1
  • Jian-Lin Huang
    • 1
  • Ming-Xing Qiu
    • 1
  • Zhi-Wei Ma
    • 1
  1. 1.Department of UrologySichuan Academy of Medical Sciences & Sichuan Provincial People’s HospitalChengduChina

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