Advertisement

World Journal of Urology

, Volume 34, Issue 4, pp 607–611 | Cite as

Vitamin D and prostate cancer prognosis: a Mendelian randomization study

  • Olivia Trummer
  • Uwe Langsenlehner
  • Sabine Krenn-Pilko
  • Thomas R. Pieber
  • Barbara Obermayer-Pietsch
  • Armin Gerger
  • Wilfried RennerEmail author
  • Tanja Langsenlehner
Original Article

Abstract

Purpose

Decreased vitamin D levels have been associated with prostate cancer, but it is unclear whether this association is causal. A functional single-nucleotide polymorphism (SNP) in the group-specific component (GC) gene (T > G, rs2282679) has been associated with 25-hydroxy (25-OH) vitamin D and 1.25 dihydroxy (1.25-OH2) vitamin D levels.

Methods

To examine the hypothesized inverse relationship between vitamin D status and prostate cancer, we studied the association between this SNP and prostate cancer outcome in the prospective PROCAGENE study comprising 702 prostate cancer patients with a median follow-up of 82 months.

Results

GC rs2282679 genotypes were not associated with biochemical recurrence [hazard ratios (HR) 0.91, 95 % confidence interval (CI) 0.73–1.12; p = 0.36], development of metastases (HR 1.20, 95 % CI 0.88–1.63; p = 0.25) or overall survival (HR 1.10; 95 % CI 0.84–1.43; p = 0.50).

Conclusions

A causal role of vitamin D status, as reflected by GC rs2282679 genotype, in disease progression and mortality in prostate cancer patients is unlikely.

Keywords

Vitamin D Prostate cancer Genetics 

Notes

Acknowledgments

This work was supported by BioPersMed (COMET K-Project 825329), which is funded by the Federal Ministry of Transport, Innovation and Technology (BMVIT) and the Federal Ministry of Economics and Labour/the Federal Ministry of Economy, Family and Youth (BMWA/BMWFJ) and the Styrian Business Promotion Agency (SFG). This study was also supported by the Anniversary Fund of the Österreichische Nationalbank, Grant No. 11686.

Authors contribution

O. Trummer: Protocol/project development, Data collection or management, Data analysis, Manuscript writing/editing. U. Langsenlehner: Data collection or management. S. Krenn-Pilko: Data collection or management. T.R. Pieber: Protocol/project development. B. Obermayer-Pietsch: Protocol/project development, Manuscript writing/editing. A. Gerger: Protocol/project development, Manuscript writing/editing. W. Renner: Protocol/project development, Data collection or management, Data analysis, Manuscript writing/editing. T. Langsenlehner: Protocol/project development, Data collection or management, Manuscript writing/editing.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical standards

The study has been approved by the Ethical Committee of the Medical University of Graz and has therefore been performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments. Written informed consent was obtained from all participating subjects.

References

  1. 1.
    Swami S, Krishnan AV, Feldman D (2011) Vitamin D metabolism and action in the prostate: implications for health and disease. Mol Cell Endocrinol 347:61–69CrossRefPubMedPubMedCentralGoogle Scholar
  2. 2.
    Jones G, Strugnell SA, DeLuca HF (1998) Current understanding of the molecular actions of vitamin D. Physiol Rev 78:1193–1231PubMedGoogle Scholar
  3. 3.
    Chen TC, Holick MF (2003) Vitamin D and prostate cancer prevention and treatment. Trends. Endocrinol Metabol. 14:423–430CrossRefGoogle Scholar
  4. 4.
    Giovannucci E (1998) Dietary influences of 1,25(OH)2 vitamin D in relation to prostate cancer: a hypothesis. Cancer Causes Control 9:567–582CrossRefPubMedGoogle Scholar
  5. 5.
    Holick MF (2006) Resurrection of vitamin D deficiency and rickets. J Clin Invest. 116:2062–2072CrossRefPubMedPubMedCentralGoogle Scholar
  6. 6.
    Peehl DM, Feldman D (2003) The role of vitamin D and retinoids in controlling prostate cancer progression. Endocr Relat Cancer 10:131–140CrossRefPubMedGoogle Scholar
  7. 7.
    Young MV, Schwartz GG, Wang L, Jamieson DP, Whitlatch LW, Flanagan JN, Lokeshwar BL, Holick MF, Chen TC (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 25:967–971CrossRefPubMedGoogle Scholar
  8. 8.
    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 88:315–322CrossRefPubMedGoogle Scholar
  9. 9.
    Giovannucci E (2005) The epidemiology of vitamin D and cancer incidence and mortality: a review (United States). Cancer Causes Control 16:83–95CrossRefPubMedGoogle Scholar
  10. 10.
    Jones G, Strugnell SA, DeLuca HF (1998) Current understanding of the molecular actions of vitamin D. Physiol Rev 78:1193–1231PubMedGoogle Scholar
  11. 11.
    Chen TC, Holick MF (2003) Vitamin D and prostate cancer prevention and treatment. Trends Endocrinol Metabol. 14:423–430CrossRefGoogle Scholar
  12. 12.
    Gozdzik A, Zhu J, Wong BY, Fu L, Cole DE, Parra EJ (2011) Association of vitamin D binding protein (VDBP) polymorphisms and serum 25(OH)D concentrations in a sample of young Canadian adults of different ancestry. J Steroid Biochem Mol Biol 127:405–412CrossRefPubMedGoogle Scholar
  13. 13.
    Speeckaert M, Huang G, Delanghe JR, Taes YE (2006) Biological and clinical aspects of the vitamin D binding protein (Gc-globulin) and its polymorphism. Clin Chim Acta 372:33–42CrossRefPubMedGoogle Scholar
  14. 14.
    Wang TJ, Zhang F, Richards JB, Kestenbaum B, van Meurs JB, Berry D, Kiel DP, Streeten EA, Ohlsson C, Koller DL, Peltonen L, Cooper JD, O’Reilly PF, Houston DK, Glazer NL, Vandenput L, Peacock M, Shi J, Rivadeneira F, McCarthy MI, Anneli P, de Boer IH, Mangino M, Kato B, Smyth DJ, Booth SL, Jacques PF, Burke GL, Goodarzi M, Cheung CL, Wolf M, Rice K, Goltzman D, Hidiroglou N, Ladouceur M, Wareham NJ, Hocking LJ, Hart D, Arden NK, Cooper C, Malik S, Fraser WD, Hartikainen AL, Zhai G, Macdonald HM, Forouhi NG, Loos RJ, Reid DM, Hakim A, Dennison E, Liu Y, Power C, Stevens HE, Jaana L, Vasan RS, Soranzo N, Bojunga J, Psaty BM, Lorentzon M, Foroud T, Harris TB, Hofman A, Jansson JO, Cauley JA, Uitterlinden AG, Gibson Q, Jarvelin MR, Karasik D, Siscovick DS, Econs MJ, Kritchevsky SB, Florez JC, Todd JA, Dupuis J, Hypponen E, Spector TD (2010) Common genetic determinants of vitamin D insufficiency: a genome-wide association study. Lancet 376:180–188CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Ahn J, Yu K, Stolzenberg-Solomon R, Simon KC, McCullough ML, Gallicchio L, Jacobs EJ, Ascherio A, Helzlsouer K, Jacobs KB, Li Q, Weinstein SJ, Purdue M, Virtamo J, Horst R, Wheeler W, Chanock S, Hunter DJ, Hayes RB, Kraft P, Albanes D (2010) Genome-wide association study of circulating vitamin D levels. Hum Mol Genet 19:2739–2745CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    Langsenlehner T, Langsenlehner U, Renner W, Kapp KS, Krippl P, Hofmann G, Clar H, Pummer K, Mayer R (2008) The Glu228Ala polymorphism in the ligand binding domain of death receptor 4 is associated with increased risk for prostate cancer metastases. Prostate 15(68):264–268CrossRefGoogle Scholar
  17. 17.
    Mohler J, Bahnson RR, Boston B, Busby JE, D’Amico A, Eastham JA et al (2010) NCCN clinical practice guidelines in oncology: prostate cancer. J Natl Compr Canc Netw 8:162–200PubMedGoogle Scholar
  18. 18.
    Roach M III, Hanks G, Thames H Jr et al (2006) Defining biochemical failure following radiotherapy with or without hormonal therapy in men with clinically localized prostate cancer: recommendations of the RTOG-ASTRO phoenix consensus conference. Int J Radiat Oncol Biol Phys 65:965–974CrossRefPubMedGoogle Scholar
  19. 19.
    Schemper M, Smith TL (1996) A note on quantifying follow-up in studies of failure time. Control Clin Trials 17:343–346CrossRefPubMedGoogle Scholar
  20. 20.
    Gilbert R, Martin RM, Beynon R, Harris R, Savovic J, Zuccolo L, Bekkering GE, Fraser WD, Sterne JA, Metcalfe C (2011) Associations of circulating and dietary vitamin D with prostate cancer risk: a systematic review and dose-response meta-analysis. Cancer Causes Control 22:319–340CrossRefPubMedGoogle Scholar
  21. 21.
    Mondul AM, Shui IM, Yu K, Weinstein SJ, Tsilidis KK, Joshi AD, Agudo A, Berg CD, Black A, Buring JE, Chasman DI, Gaudet MM, Haiman C, Hankinson SE, Henderson BE, Hoover RN, Hunter DJ, Khaw KT, Kühn T, Kvaskoff M, Le Marchand L, Lindström S, McCullough ML, Overvad K, Peeters PH, Riboli E, Ridker PM, Stram DO, Sund M, Trichopoulos D, Tumino R, Weiderpass E, Willett W, Kraft P, Ziegler RG, Albanes D (2015) Vitamin D-associated genetic variation and risk of breast cancer in the breast and prostate cancer cohort consortium (BPC3). Cancer Epidemiol Biomark Prev 24:627–630CrossRefGoogle Scholar
  22. 22.
    Davies JR, Field S, Randerson-Moor J, Harland M, Kumar R, Anic GM, Nagore E, Hansson J, Höiom V, Jönsson G, Gruis NA, Park JY, Guan J, Sivaramakrishna Rachakonda P, Wendt J, Pjanova D, Puig S, Schadendorf D, Okamoto I, Olsson H, Affleck P, García-Casado Z, Puig-Butille JA, Stratigos AJ, Kodela E, Donina S, Sucker A, Hosen I, Egan KM, Barrett JH, van Doorn R, Bishop DT, Newton-Bishop J (2014) An inherited variant in the gene coding for vitamin D-binding protein and survival from cutaneous melanoma: a BioGenoMEL study. Pigment Cell Melanoma Res. 27:234–243CrossRefPubMedPubMedCentralGoogle Scholar
  23. 23.
    Theodoratou E, Palmer T, Zgaga L, Farrington SM, McKeigue P, Din FV, Tenesa A, Davey-Smith G, Dunlop MG, Campbell H (2012) Instrumental variable estimation of the causal effect of plasma 25-hydroxy-vitamin D on colorectal cancer risk: a Mendelian randomization analysis. PLoS ONE 7:e37662CrossRefPubMedPubMedCentralGoogle Scholar
  24. 24.
    Szkandera J, Absenger G, Pichler M, Stotz M, Langsenlehner T, Samonigg H, Renner W, Gerger A (2013) Association of common gene variants in vitamin D modulating genes and colon cancer recurrence. J Cancer Res Clin Oncol 139:1457–1464CrossRefPubMedGoogle Scholar
  25. 25.
    Gilbert R, Bonilla C, Metcalfe C, Lewis S, Evans DM, Fraser WD, Kemp JP, Donovan JL, Hamdy FC, Neal DE, Lane JA, Smith GD, Lathrop M, Martin RM (2015) Associations of vitamin D pathway genes with circulating 25-hydroxyvitamin-D, 1,25-dihydroxyvitamin-D, and prostate cancer: a nested case-control study. Cancer Causes Control 26:205–218CrossRefPubMedPubMedCentralGoogle Scholar
  26. 26.
    Bolla M, de Reijke TM, Van Tienhoven G, Van den Bergh AC, Oddens J, Poortmans PM et al (2009) Duration of androgen suppression in the treatment of prostate cancer. N Engl J Med 360:2516–2527CrossRefPubMedGoogle Scholar
  27. 27.
    Horwitz EM, Bae K, Hanks GE, Porter A, Grignon DJ, Brereton HD et al (2008) Ten-year follow-up of radiation therapy oncology group protocol 92-02: a phase III trial of the duration of elective androgen deprivation in locally advanced prostate cancer. J Clin Oncol 26:2497–2504CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2015

Authors and Affiliations

  • Olivia Trummer
    • 1
  • Uwe Langsenlehner
    • 2
  • Sabine Krenn-Pilko
    • 3
  • Thomas R. Pieber
    • 1
  • Barbara Obermayer-Pietsch
    • 1
  • Armin Gerger
    • 4
  • Wilfried Renner
    • 5
    Email author
  • Tanja Langsenlehner
    • 3
  1. 1.Division of Endocrinology and Metabolism, Department of Internal MedicineMedical University of GrazGrazAustria
  2. 2.Division of Internal MedicineGKK Outpatient DepartmentGrazAustria
  3. 3.Department of Therapeutic Radiology and OncologyMedical University of GrazGrazAustria
  4. 4.Division of Oncology, Department of Internal MedicineMedical University of GrazGrazAustria
  5. 5.Clinical Institute of Medical and Chemical Laboratory DiagnosticsMedical University of GrazGrazAustria

Personalised recommendations