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Vol. 129, No. 2, 2013
Issue release date: February 2013

Association between CYP2C8 (rs1934951) Polymorphism and Bisphosphonate-Related Osteonecrosis of the Jaws in Patients on Bisphosphonate Therapy: A Meta-Analysis

Zhong D.-N. · Wu J.-Z. · Li G.-J.
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Abstract

Aims: Bisphosphonate-related osteonecrosis of the jaws (BONJ) is a severe complication in patients on bisphosphonate therapy. The study was conducted to verify the association between CYP2C8 (rs1934951) polymorphism and BONJ predisposition. Methods: The relative epidemiologic studies were identified in PubMed and Embase to conduct a meta-analysis using STATA. Results: In the pooled analysis with multiple cancer types, patients carrying the CYP2C8 rs1934951 AA or AG genotype showed no significantly increased BONJ susceptibility compared with those carrying the wild GG genotype [dominant: odds ratio (OR) = 2.05, 95% confidence interval (CI) = 0.67–6.29, p = 0.209; recessive: OR = 1.88, 95% CI = 0.23–15.6, p = 0.560; AG vs. GG: OR = 2.07, 95% CI = 0.80–5.32, p = 0.133, and AA vs. GG: OR = 1.34, 95% CI = 0.48–3.74, p = 0.578]. A significant association between AA and AG genotypes of CYP2C8 (rs1934951) and BONJ risk was found in the subgroup analysis of multiple myeloma (dominant: OR = 5.77, 95% CI = 1.21–27.63, p = 0.028; AG vs. GG: OR = 5.02, 95% CI = 2.06–12.23, p = 0.001, and AA vs. GG: OR = 16.23, 95% CI = 1.72–78.7, p = 0.015). Conclusion: The results indicated that AA and AG genotypes of CYP2C8 (rs1934951) might be predictors for multiple myeloma patients at high risk to develop BONJ.



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References

  1. Aft R: Bisphosphonates in breast cancer: clinical activity and implications of preclinical data. Clin Adv Hematol Oncol 2011;9:194–205.
  2. Gnant M, Hadji P: Prevention of bone metastases and management of bone health in early breast cancer. Breast Cancer Res 2010;12:216.
  3. Pozzi S, Raje N: The role of bisphosphonates in multiple myeloma: mechanisms, side effects, and the future. Oncologist 2011;16:651–662.
  4. Marx RE: Pamidronate (Aredia) and zoledronate (Zometa) induced avascular necrosis of the jaws: a growing epidemic. J Oral Maxillofac Surg 2003;61:1115–1117.
  5. Walter C, Al-Nawas B, Grotz KA, Thomas C, Thuroff JW, Zinser V, Gamm H, Beck J, Wagner W: Prevalence and risk factors of bisphosphonate-associated osteonecrosis of the jaw in prostate cancer patients with advanced disease treated with zoledronate. Eur Urol 2008;54:1066–1072.

    External Resources

  6. Stumpe MR, Chandra RK, Yunus F, Samant S: Incidence and risk factors of bisphosphonate-associated osteonecrosis of the jaws. Head Neck 2009;31:202–206.

    External Resources

  7. Ruggiero SL, Dodson TB, Assael LA, Landesberg R, Marx RE, Mehrotra B: American Association of Oral and Maxillofacial Surgeons position paper on bisphosphonate-related osteonecrosis of the jaws – 2009 update. J Oral Maxillofac Surg 2009;67:2–12.

    External Resources

  8. O’Ryan FS, Khoury S, Liao W, Han MM, Hui RL, Baer D, Martin D, Liberty D, Lo JC: Intravenous bisphosphonate-related osteonecrosis of the jaw: bone scintigraphy as an early indicator. J Oral Maxillofac Surg 2009;67:1363–1372.

    External Resources

  9. Otto S, Pautke C, Opelz C, Westphal I, Drosse I, Schwager J, Bauss F, Ehrenfeld M, Schieker M: Osteonecrosis of the jaw: effect of bisphosphonate type, local concentration, and acidic milieu on the pathomechanism. J Oral Maxillofac Surg 2010;68:2837–2845.

    External Resources

  10. Pazianas M, Miller P, Blumentals WA, Bernal M, Kothawala PA: Review of the literature on osteonecrosis of the jaw in patients with osteoporosis treated with oral bisphosphonates: prevalence, risk factors, and clinical characteristics. Clin Ther 2007;29:1548–1558.
  11. Sarasquete ME, Garcia-Sanz R, Marin L, Alcoceba M, Chillon MC, Balanzategui A, Santamaria C, Rosinol L, de la Rubia J, Hernandez MT, Garcia-Navarro I, Lahuerta JJ, Gonzalez M, San Miguel JF: Bisphosphonate-related osteonecrosis of the jaw is associated with polymorphisms of the cytochrome P450 CYP2C8 in multiple myeloma: a genome-wide single nucleotide polymorphism analysis. Blood 2008;112:2709–2712.
  12. Such E, Cervera J, Terpos E, Bagan JV, Avaria A, Gomez I, Margaix M, Ibanez M, Luna I, Cordon L, Roig M, Sanz MA, Dimopoulos MA, de la Rubia J: CYP2C8 gene polymorphism and bisphosphonate-related osteonecrosis of the jaw in patients with multiple myeloma. Haematologica 2011;96:1557–1559.

    External Resources

  13. Lai XS, Yang LP, Li XT, Liu JP, Zhou ZW, Zhou SF: Human CYP2C8: structure, substrate specificity, inhibitor selectivity, inducers and polymorphisms. Curr Drug Metab 2009;10:1009–1047.
  14. Soh TI, Yong WP, Innocenti F: Recent progress and clinical importance on pharmacogenetics in cancer therapy. Clin Chem Lab Med 2011;49:1621–1632.
  15. Higgins JP, Thompson SG, Deeks JJ, Altman DG: Measuring inconsistency in meta-analyses. BMJ 2003;327:557–560.
  16. Begg CB, Mazumdar M: Operating characteristics of a rank correlation test for publication bias. Biometrics 1994;50:1088–1101.
  17. Egger M, Davey Smith G, Schneider M, Minder C: Bias in meta-analysis detected by a simple, graphical test. BMJ 1997;315:629–634.
  18. English BC, Baum CE, Adelberg DE, Sissung TM, Kluetz PG, Dahut WL, Price DK, Figg WD: A SNP in CYP2C8 is not associated with the development of bisphosphonate-related osteonecrosis of the jaw in men with castrate-resistant prostate cancer. Ther Clin Risk Manag 2010;6:579–583.
  19. Balla B, Vaszilko M, Kosa J, Podani J, Takacs I, Tobias B, Nagy Z, Lazary A, Lakatos P: New approach to analyze genetic and clinical data in bisphosphonate-induced osteonecrosis of the jaw. Oral Dis 2012;18:580–585.
  20. Katz J, Gong Y, Salmasinia D, Hou W, Burkley B, Ferreira P, Casanova O, Langaee TY, Moreb JS: Genetic polymorphisms and other risk factors associated with bisphosphonate induced osteonecrosis of the jaw. Int J Oral Maxillofac Surg 2011;40:605–611.
  21. Chowbay B, Li H, David M, Cheung YB, Lee EJ: Meta-analysis of the influence of MDR1 C3435T polymorphism on digoxin pharmacokinetics and MDR1 gene expression. Br J Clin Pharmacol 2005;60:159–171.
  22. Kiyohara C, Yoshimasu K: Genetic polymorphisms in the nucleotide excision repair pathway and lung cancer risk: a meta-analysis. Int J Med Sci 2007;4:59–71.
  23. Jung TI, Hoffmann F, Glaeske G, Felsenberg D: Disease-specific risk for an osteonecrosis of the jaw under bisphosphonate therapy. J Cancer Res Clin Oncol 2010;136:363–370.
  24. Daly AK: Genome-wide association studies in pharmacogenomics. Nat Rev Genet 2010;11:241–246.
  25. Li SC, Tang P, Lin WC: Intronic microRNA: discovery and biological implications. DNA Cell Biol 2007;26:195–207.

    External Resources

  26. Monteys AM, Spengler RM, Wan J, Tecedor L, Lennox KA, Xing Y, Davidson BL: Structure and activity of putative intronic miRNA promoters. RNA 2010;16:495–505.

    External Resources

  27. Dimopoulos MA, Kastritis E, Anagnostopoulos A, Melakopoulos I, Gika D, Moulopoulos LA, Bamia C, Terpos E, Tsionos K, Bamias A: Osteonecrosis of the jaw in patients with multiple myeloma treated with bisphosphonates: evidence of increased risk after treatment with zoledronic acid. Haematologica 2006;91:968–971.


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