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Lack of association between vitamin D receptor gene FokI and BsmI polymorphisms and prostate cancer risk: an updated meta-analysis involving 21,756 subjects

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Tumor Biology

Abstract

The vitamin D receptor (VDR) is a crucial mediator for the cellular effects of vitamin D. The polymorphisms in the VDR gene have been hypothesized to alter the risk of prostate cancer. However, studies investigating the association between VDR polymorphisms (BsmI and FokI) and prostate cancer (PCa) risk report conflicting results , therefore, we conducted a meta-analysis to re-examine the controversy. Published literatures from PubMed, Embase, Google Scholar, and China National Knowledge Infrastructure (CNKI) were searched (updated to March 9, 2013). According to our inclusion criteria, studies that observed the association between VDR BsmI and FokI polymorphisms and PCa risk were included. The principal outcome measure was the odds ratio (OR) with 95 % confidence interval (CI) for PCa risk associated with VDR BsmI and FokI polymorphisms. Thirty-four studies involving 10,267 cases and 11,489 controls were recruited. Overall, we did not find evidence to support an association between any of the VDR polymorphisms and PCa risk. For BsmI, the pooled OR was 0.894 (95 % CI 0.773 to 1.034) for the Bb vs. bb genotypes, 1.002 (95 % CI 0.869 to 1.157) for the BB vs. bb genotypes, 0.922 (95 % CI 0.798 to 1.065) for the dominant model (BB/Bb vs. bb), and 1.018 (95 % CI 0.936 to 1.107) for the recessive model (BB vs. Bb/bb). ORs for the FokI polymorphisms were similar. The results suggest that the VDR BsmI and FokI polymorphisms are not related to PCa risk. Further large and well-designed studies are required to confirm this conclusion.

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References

  1. Heidenreich A, Bellmunt J, Bolla M, et al. EAU guidelines on prostate cancer. Part 1: screening, diagnosis, and treatment of clinically localised disease. Eur Urol. 2011;59:61–71.

    Article  PubMed  Google Scholar 

  2. Boyle P, Ferlay J. Cancer incidence and mortality in Europe, 2004. Ann Oncol. 2005;16:481–8.

    Article  CAS  PubMed  Google Scholar 

  3. Fleshner N, Zlotta AR. Prostate cancer prevention: past, present, and future. Cancer. 2007;110:1889–99.

    Article  CAS  PubMed  Google Scholar 

  4. American Cancer Society: Cancer Facts & Figures 2009. 2009.

  5. Schwartz GG, Hulka BS. Is vitamin D deficiency a risk factor for prostate cancer? (Hypothesis). Anticancer Res. 1990;10:1307–11.

    CAS  PubMed  Google Scholar 

  6. Peehl DM, Skowronski RJ, Leung GK, Wong ST, Stamey TA, Feldman D. Antiproliferative effects of 1,25-dihydroxyvitamin D3 on primary cultures of human prostatic cells. Cancer Res. 1994;54:805–10.

    CAS  PubMed  Google Scholar 

  7. Miller GJ, Stapleton GE, Hedlund TE, Moffat KA. Vitamin D receptor expression, 24-hydroxylase activity, and inhibition of growth by 1alpha,25-dihydroxyvitamin D3 in seven human prostatic carcinoma cell lines. Clin Cancer Res. 1995;1:997–1003.

    CAS  PubMed  Google Scholar 

  8. Hedlund TE, Moffatt KA, Miller GJ. Vitamin D receptor expression is required for growth modulation by 1 alpha,25-dihydroxyvitamin D3 in the human prostatic carcinoma cell line ALVA-31. J Steroid Biochem Mol Biol. 1996;58:277–88.

    Article  CAS  PubMed  Google Scholar 

  9. Raimondi S, Johansson H, Maisonneuve P, Gandini S. Review and meta-analysis on vitamin D receptor polymorphisms and cancer risk. Carcinogenesis. 2009;30:1170–80.

    Article  CAS  PubMed  Google Scholar 

  10. Whitfield GK, Remus LS, Jurutka PW, et al. Functionally relevant polymorphisms in the human nuclear vitamin D receptor gene. Mol Cell Endocrinol. 2001;177:145–59.

    Article  CAS  PubMed  Google Scholar 

  11. Uitterlinden AG, Fang Y, Van Meurs JB, Pols HA, Van Leeuwen JP. Genetics and biology of vitamin D receptor polymorphisms. Gene. 2004;338:143–56.

    Article  CAS  PubMed  Google Scholar 

  12. Ntais C, Polycarpou A, Ioannidis JP. Vitamin D receptor gene polymorphisms and risk of prostate cancer: a meta-analysis. Cancer Epidemiol BiomarkPrev. 2003;12:1395–402.

    CAS  Google Scholar 

  13. Berndt SI, Dodson JL, Huang WY, Nicodemus KK. A systematic review of vitamin D receptor gene polymorphisms and prostate cancer risk. J Urol. 2006;175:1613–23.

    Article  CAS  PubMed  Google Scholar 

  14. Cochran WG. The combination of estimates from different experiments. Biometrics. 1954;10:101–29.

    Article  Google Scholar 

  15. Mantel N, Haenszel W. Statistical aspects of the analysis of data from retrospective studies of disease. J Natl Cancer Inst. 1959;22:719–48.

    CAS  PubMed  Google Scholar 

  16. DerSimonian R, Laird N. Meta-analysis in clinical trials. Control Clin Trials. 1986;7:177–88.

    Article  CAS  PubMed  Google Scholar 

  17. Tobias A. Assessing the influence of a single study in the meta-analysis estimate. Stata Tech Bull. 1999;8:15–7.

    Google Scholar 

  18. Egger M, Davey Smith G, Schneider M, Minder C. Bias in metaanalysis detected by a simple, graphical test. BMJ. 1997;315:629–34.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  19. Li H, Stampfer MJ, Hollis JB, et al. A prospective study of plasma vitamin D metabolites, vitamin D receptor polymorphisms, and prostate cancer. PLoS Med. 2007;4:e103.

    Article  PubMed Central  PubMed  Google Scholar 

  20. Yang Y, Wang S, Ye Z, Yang W. Association of single nucleotide polymorphism of vitamin D receptor gene start codon and the susceptibility to prostate cancer in the Han nationality in Hubei area. Zhonghua Nan Ke Xue. 2004;10:411–4 [Article in Chinese].

    CAS  PubMed  Google Scholar 

  21. Huang SP, Huang CY, Wu WJ, et al. Association of vitamin D receptor FokI polymorphism with prostate cancer risk, clinicopathological features and recurrence of prostate specific antigen after radical prostatectomy. Int J Cancer. 2006;119:1902–7.

    Article  CAS  PubMed  Google Scholar 

  22. Mishra DK, Bid HK, Srivastava DS, Mandhani A, Mittal RD. Association of vitamin D receptor gene polymorphism and risk of prostate cancer in India. Urol Int. 2005;74:315–8.

    Article  CAS  PubMed  Google Scholar 

  23. Bai Y, Yu Y, Yu B, et al. Association of vitamin D receptor polymorphisms with the risk of prostate cancer in the Han population of Southern China. BMC Med Genet. 2009;10:125.

    Article  PubMed Central  PubMed  Google Scholar 

  24. Holick CN, Stanford JL, Kwon EM, Ostrander EA, Nejentsev S, Peters U. Comprehensive association analysis of the vitamin D pathway genes, VDR, CYP27B1, and CYP24A1, in prostate cancer. Cancer Epidemiol Biomark Prev. 2007;16:1990–9.

    Article  CAS  Google Scholar 

  25. Hayes VM, Severi G, Padilla EJ, et al. Genetic variants in the vitamin D receptor gene and prostate cancer risk. Cancer Epidemiol Biomark Prev. 2005;14:997–9.

    Article  CAS  Google Scholar 

  26. Bodiwala D, Luscombe CJ, French ME, et al. Polymorphisms in the vitamin D receptor gene, ultraviolet radiation, and susceptibility to prostate cancer. Environ Mol Mutagen. 2004;43:121–7.

    Article  CAS  PubMed  Google Scholar 

  27. Rukin NJ, Luscombe C, Moon S, et al. Prostate cancer susceptibility is mediated by interactions between exposure to ultraviolet radiation and polymorphisms in the 5' haplotype block of the vitamin D receptor gene. Cancer Lett. 2007;247:328–35.

    Article  CAS  PubMed  Google Scholar 

  28. Oakley-Girvan I, Feldman D, Eccleshall TR, et al. Risk of early-onset prostate cancer in relation to germ line polymorphisms of the vitamin D receptor. Cancer Epidemiol Biomark Prev. 2004;13:1325–30. 1/2.

    CAS  Google Scholar 

  29. John EM, Schwartz GG, Koo J, Van Den Berg D, Ingles SA. Sun exposure, vitamin D receptor gene polymorphisms, and risk of advanced prostate cancer. Cancer Res. 2005;65:5470–9.

    Article  CAS  PubMed  Google Scholar 

  30. Torkko KC, van Bokhoven A, Mai P, et al. VDR and SRD5A2 polymorphisms combine to increase risk for prostate cancer in both non-Hispanic White and Hispanic White men. Clin Cancer Res. 2008;14:3223–9. 1/2.

    Article  CAS  PubMed  Google Scholar 

  31. Ruan L, Li Z, Li G. Relationship between snp of vitamin d receptor start codon and prostate cancer. IMHGN. 2009;15:12–4. Article in Chinese.

    Google Scholar 

  32. Holt SK, Kwon EM, Peters U, Ostrander EA, Stanford JL. Vitamin D pathway gene variants and prostate cancer risk. Cancer Epidemiol Biomark Prev. 2009;18:1929–33. 1/2.

    Article  CAS  Google Scholar 

  33. Mikhak B, Hunter DJ, Spiegelman D, Platz EA, Hollis BW, Giovannucci E. Vitamin D receptor (VDR) gene polymorphisms and haplotypes, interactions with plasma 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D, and prostate cancer risk. Prostate. 2007;67:911–23.

    Article  CAS  PubMed  Google Scholar 

  34. Chokkalingam AP, McGlynn KA, Gao YT, et al. Vitamin D receptor gene polymorphisms, insulin-like growth factors, and prostate cancer risk: a population-based case–control study in China. Cancer Res. 2001;61:4333–6.

    CAS  PubMed  Google Scholar 

  35. Cicek MS, Liu X, Schumacher FR, Casey G, Witte JS. Vitamin D receptor genotypes/haplotypes and prostate cancer risk. Cancer Epidemiol Biomark Prev. 2006;15:2549–52.

    Article  CAS  Google Scholar 

  36. Correa-Cerro L, Berthon P, Häussler J, et al. Vitamin D receptor polymorphisms as markers in prostate cancer. Hum Genet. 1999;105:281–7.

    Article  CAS  PubMed  Google Scholar 

  37. Tayeb MT, Clark C, Haites NE, Sharp L, Murray GI, McLeod HL. Vitamin D receptor, HER-2 polymorphisms and risk of prostate cancer in men with benign prostate hyperplasia. Saudi Med J. 2004;25:447–51.

    PubMed  Google Scholar 

  38. Cheteri MB, Stanford JL, Friedrichsen DM, et al. Vitamin D receptor gene polymorphisms and prostate cancer risk. Prostate. 2004;59:409–18.

    Article  CAS  PubMed  Google Scholar 

  39. Szendroi A, Speer G, Tabak A, et al. The role of vitamin D, estrogen, calcium sensing receptor genotypes and serum calcium in the pathogenesis of prostate cancer. Can J Urol. 2011;18:5710–6.

    PubMed  Google Scholar 

  40. Huang SP, Chou YH, Wayne Chang WS, et al. Association between vitamin D receptor polymorphisms and prostate cancer risk in a Taiwanese population. Cancer Lett. 2004;207:69–77.

    Article  CAS  PubMed  Google Scholar 

  41. Onen IH, Ekmekci A, Eroglu M, Konac E, Yesil S, Biri H. Association of genetic polymorphisms in vitamin D receptor gene and susceptibility to sporadic prostate cancer. Exp Biol Med (Maywood). 2008;233:1608–14.

    Article  CAS  Google Scholar 

  42. Ingles SA, Coetzee GA, Ross RK, et al. Association of prostate cancer with vitamin D receptor haplotypes in African-Americans. Cancer Res. 1998;58:1620–3.

    CAS  PubMed  Google Scholar 

  43. Habuchi T, Suzuki T, Sasaki R, et al. Association of vitamin D receptor gene polymorphism with prostate cancer and benign prostatic hyperplasia in a Japanese population. Cancer Res. 2000;60:305–8.

    CAS  PubMed  Google Scholar 

  44. Nam RK, Zhang WW, Trachtenberg J, et al. Comprehensive assessment of candidate genes and serological markers for the detection of prostate cancer. Cancer Epidemiol Biomark Prev. 2003;12:1429–37. 1/2/3.

    CAS  Google Scholar 

  45. Suzuki K, Matsui H, Ohtake N, et al. Vitamin D receptor gene polymorphism in familial prostate cancer in a Japanese population. Int J Urol. 2003;10:261–6.

    Article  CAS  PubMed  Google Scholar 

  46. Ma J, Stampfer MJ, Gann PH, et al. Vitamin D receptor polymorphisms, circulating vitamin D metabolites, and risk of prostate cancer in United States physicians. Cancer Epidemiol Biomark Prev. 1998;7:385–90.

    CAS  Google Scholar 

  47. Liu JH, Li HW, Wang JQ, et al. Vitamin D receptor gene Bsm I polymorphism and the susceptibility to prostate cancer in northern Chinese Han population. Zhonghua Nan Ke Xue. 2003;9:413–6. Article in Chinese.

    CAS  PubMed  Google Scholar 

  48. Nejentsev S, Godfrey L, Snook H, et al. Comparative high-resolution analysis of linkage disequilibrium and tag single nucleotide polymorphisms between populations in the vitamin D receptor gene. Hum Mol Genet. 2004;13:1633–9.

    Article  CAS  PubMed  Google Scholar 

  49. Vélayoudom-Céphise FL, Larifla L, Donnet JP, et al. Vitamin D deficiency, vitamin D receptor gene polymorphisms and cardiovascular risk factors in Caribbean patients with type 2 diabetes. Diabetes Metab. 2011;37:540–5.

    Article  PubMed  Google Scholar 

  50. Han X, Xue L, Li Y, Chen B, Xie A. Vitamin D receptor gene polymorphism and its association with Parkinson's disease in Chinese Han population. Neurosci Lett. 2012;525:29–33.

    Article  CAS  PubMed  Google Scholar 

  51. Wang Q, Xi B, Reilly KH, Liu M, Fu M. Quantitative assessment of the associations between four polymorphisms (FokI, ApaI, BsmI, TaqI) of vitamin D receptor gene and risk of diabetes mellitus. Mol Biol Rep. 2012;39:9405–14.

    Article  CAS  PubMed  Google Scholar 

  52. Bousema JT, Bussemakers MJ, van Houwelingen KP, et al. Polymorphisms in the vitamin D receptor gene and the androgen receptor gene and the risk of benign prostatic hyperplasia. Eur Urol. 2000;37:234–8.

    Article  CAS  PubMed  Google Scholar 

  53. Zintzaras E, Ioannidis JP. Heterogeneity testing in meta-analysis of genome searches. Genet Epidemiol. 2005;28:123–37.

    Article  PubMed  Google Scholar 

  54. Lin PI, Vance JM, Pericak-Vance MA, Martin ER. No gene is an island: the flip-flop phenomenon. Am J Hum Genet. 2007;80:531–8.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

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Acknowledgments

This study was supported by “The Youth Innovation Fund of the First Affiliated Hospital of Zhengzhou University” and “Foundation of Henan Educational Committee (No. 13A320688)”.

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Authors and Affiliations

  1. The Institute of Clinical Medicine, The First Affiliated Hospital of Zhengzhou University, Henan, 450052, China

    Zhan Guo, Jianguo Wen, Quancheng Kan, Shuman Huang & Zhenzhen Li

  2. Urology Department and Pediatric Urodynamic Center, Henan, China

    Zhan Guo, Jianguo Wen & Shuman Huang

  3. Pharmacy Department, The First Affiliated Hospital of Zhengzhou University, Henan, China

    Quancheng Kan

  4. Henan University of Traditional Chinese Medicine, Henan, China

    Xianghua Liu & Ning Sun

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  1. Zhan Guo
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Correspondence to Zhenzhen Li.

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Zhan Guo and Jianguo Wen contributed equally to this work.

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Guo, Z., Wen, J., Kan, Q. et al. Lack of association between vitamin D receptor gene FokI and BsmI polymorphisms and prostate cancer risk: an updated meta-analysis involving 21,756 subjects. Tumor Biol. 34, 3189–3200 (2013). https://doi.org/10.1007/s13277-013-0889-6

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  • DOI: https://doi.org/10.1007/s13277-013-0889-6

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