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The polymorphism IL-1β T-31C is associated with a longer overall survival in patients with multiple myeloma undergoing auto-SCT

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Abstract

Proinflammatory cytokines are suspected to play a role in the pathogenesis of multiple myeloma (MM). Therefore, it is possible that inborn genetic variations leading to a modified expression of these cytokines will influence the outcome for these patients. We investigated 348 MM patients undergoing high-dose melphalan treatment followed by Auto-SCT and examined the influence of single nucleotide polymorphisms (SNPs) in genes involved in the inflammatory response. We found that the polymorphism IL-1β T-31C significantly influenced overall survival (OS; P=0.02) and that carriers of the variant C-allele had a significantly longer survival than homozygous wild-type allele TT-carriers (relative risk 0.6 (95% CI=0.5–0.9); P=0.008). The polymorphisms IL-6 G-174C, IL-10 C592A, PPARγ2 Pro12Ala, COX-2 A-1195G, COX-2 T8473C and NFKB1 ins/del did not influence the OS in this group of patients. Furthermore, homozygous carriers of the variant allele of IL-1β T-31C were at 1.37-fold (CI=1.05–1.80) increased risk of MM as compared with population-based controls (P=0.02). Our results indicate that IL-1β is involved in the pathogenesis of MM.

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References

  1. Bonizzi G, Karin M . The two NF-kappaB activation pathways and their role in innate and adaptive immunity. Trends Immunol 2004; 25: 280–288.

    Article  CAS  PubMed  Google Scholar 

  2. Naugler WE, Karin M . NF-kappaB and cancer-identifying targets and mechanisms. Curr Opin Genet Dev 2008; 18: 19–26.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Ray DM, Bernstein SH, Phipps RP . Human multiple myeloma cells express peroxisome proliferator-activated receptor gamma and undergo apoptosis upon exposure to PPARgamma ligands. Clin Immunol 2004; 113: 203–213.

    Article  CAS  PubMed  Google Scholar 

  4. El Omar EM, Carrington M, Chow WH, McColl KE, Bream JH, Young HA et al. Interleukin-1 polymorphisms associated with increased risk of gastric cancer. Nature 2000; 404: 398–402.

    Article  CAS  PubMed  Google Scholar 

  5. Landi S, Moreno V, Gioia-Patricola L, Guino E, Navarro M, de Oca J et al. Association of common polymorphisms in inflammatory genes interleukin (IL)6, IL8, tumor necrosis factor alpha, NFKB1, and peroxisome proliferator-activated receptor gamma with colorectal cancer. Cancer Res 2003; 63: 3560–3566.

    CAS  PubMed  Google Scholar 

  6. Howell WM, Rose-Zerilli MJ . Interleukin-10 polymorphisms, cancer susceptibility and prognosis. Fam Cancer 2006; 5: 143–149.

    Article  CAS  PubMed  Google Scholar 

  7. Rothman N, Skibola CF, Wang SS, Morgan G, Lan Q, Smith MT et al. Genetic variation in TNF and IL10 and risk of non-Hodgkin lymphoma: a report from the InterLymph Consortium. Lancet Oncol 2006; 7: 27–38.

    Article  CAS  PubMed  Google Scholar 

  8. Zhang X, Miao X, Tan W, Ning B, Liu Z, Hong Y et al. Identification of functional genetic variants in cyclooxygenase-2 and their association with risk of esophageal cancer. Gastroenterology 2005; 129: 565–576.

    CAS  PubMed  Google Scholar 

  9. Vangsted A, Gimsing P, Klausen TW, Nexo BA, Wallin H, Andersen P et al. Polymorphisms in the genes ERCC2, XRCC3 and CD3EAP influence treatment outcome in multiple myeloma patients undergoing autologous bone marrow transplantation. Int J Cancer 2007; 120: 1036–1045.

    Article  CAS  PubMed  Google Scholar 

  10. Lenhoff S, Hjorth M, Holmberg E, Turesson I, Westin J, Nielsen JL et al. Impact on survival of high-dose therapy with autologous stem cell support in patients younger than 60 years with newly diagnosed multiple myeloma: a population-based study. Nordic Myeloma Study Group. Blood 2000; 95: 7–11.

    CAS  PubMed  Google Scholar 

  11. Lenhoff S, Hjorth M, Westin J, Brinch L, Backstrom B, Carlson K et al. Impact of age on survival after intensive therapy for multiple myeloma: a population-based study by the Nordic Myeloma Study Group. Br J Haematol 2006; 133: 389–396.

    Article  PubMed  Google Scholar 

  12. Mellqvist UH, Lenhoff S, Johnsen HE, Hjorth M, Holmberg E, Juliusson G et al. Cyclophosphamide plus dexamethasone is an efficient initial treatment before high-dose melphalan and autologous stem cell transplantation in patients with newly diagnosed multiple myeloma: results of a randomized comparison with vincristine, doxorubicin, and dexamethasone. Cancer 2008; 112: 129–135.

    Article  CAS  PubMed  Google Scholar 

  13. Vogel U, Christensen J, Dybdahl M, Friis S, Hansen RD, Wallin H et al. Prospective study of interaction between alcohol, NSAID use and polymorphisms in genes involved in the inflammatory response in relation to risk of colorectal cancer. Mutat Res 2007; 624: 88–100.

    Article  CAS  PubMed  Google Scholar 

  14. Miller SA, Dykes DD, Polesky HF . A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic Acids Res 1988; 16: 1215.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Saber AT, Nielsen LR, Dictor M, Hagmar L, Mikoczy Z, Wallin H . K-ras mutations in sinonasal adenocarcinomas in patients occupationally exposed to wood or leather dust. Cancer Lett 1998; 126: 59–65.

    Article  CAS  PubMed  Google Scholar 

  16. Vogel U, Christensen J, Wallin H, Friis S, Nexo BA, Tjonneland A . Polymorphisms in COX-2, NSAID use and risk of basal cell carcinoma in a prospective study of Danes. Mutat Res 2007; 617: 138–146.

    Article  CAS  PubMed  Google Scholar 

  17. Li ZW, Dalton WS . Tumor microenvironment and drug resistance in hematologic malignancies. Blood Rev 2006; 20: 333–342.

    Article  PubMed  Google Scholar 

  18. Costes V, Portier M, Lu ZY, Rossi JF, Bataille R, Klein B . Interleukin-1 in multiple myeloma: producer cells and their role in the control of IL-6 production. Br J Haematol 1998; 103: 1152–1160.

    Article  CAS  PubMed  Google Scholar 

  19. Lacy MQ, Donovan KA, Heimbach JK, Ahmann GJ, Lust JA . Comparison of interleukin-1 beta expression by in situ hybridization in monoclonal gammopathy of undetermined significance and multiple myeloma. Blood 1999; 93: 300–305.

    CAS  PubMed  Google Scholar 

  20. Xiong Y, Donovan KA, Kline MP, Gornet MK, Moon-Tasson LL, Lacy MQ et al. Identification of two groups of smoldering multiple myeloma patients who are either high or low producers of interleukin-1. J Interferon Cytokine Res 2006; 26: 83–95.

    Article  CAS  PubMed  Google Scholar 

  21. Hwang IR, Kodama T, Kikuchi S, Sakai K, Peterson LE, Graham DY et al. Effect of interleukin 1 polymorphisms on gastric mucosal interleukin 1beta production in Helicobacter pylori infection. Gastroenterology 2002; 123: 1793–1803.

    Article  CAS  PubMed  Google Scholar 

  22. Chen H, Wilkins LM, Aziz N, Cannings C, Wyllie DH, Bingle C et al. Single nucleotide polymorphisms in the human interleukin-1B gene affect transcription according to haplotype context. Hum Mol Genet 2006; 15: 519–529.

    Article  CAS  PubMed  Google Scholar 

  23. Lind H, Haugen A, Zienolddiny S . Differential binding of proteins to the IL1B-31 T/C polymorphism in lung epithelial cells. Cytokine 2007; 38: 43–48.

    Article  CAS  PubMed  Google Scholar 

  24. Acosta-Rodriguez EV, Napolitani G, Lanzavecchia A, Sallusto F . Interleukins 1beta and 6 but not transforming growth factor-beta are essential for the differentiation of interleukin 17-producing human T helper cells. Nat Immunol 2007; 8: 942–949.

    Article  CAS  PubMed  Google Scholar 

  25. Nakahara T, Urabe K, Fukagawa S, Uchi H, Inaba K, Furue M et al. Engagement of human monocyte-derived dendritic cells into interleukin (IL)-12 producers by IL-1beta+interferon (IFN)-gamma. Clin Exp Immunol 2005; 139: 476–482.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Motta MR, Castellani S, Rizzi S, Curti A, Gubinelli F, Fogli M et al. Generation of dendritic cells from CD14+ monocytes positively selected by immunomagnetic adsorption for multiple myeloma patients enrolled in a clinical trial of anti-idiotype vaccination. Br J Haematol 2003; 121: 240–250.

    Article  PubMed  Google Scholar 

  27. Mazur G, Bogunia-Kubik K, Wrobel T, Karabon L, Polak M, Kuliczkowski K et al. IL-6 and IL-10 promoter gene polymorphisms do not associate with the susceptibility for multiple myeloma. Immunol Lett 2005; 96: 241–246.

    Article  CAS  PubMed  Google Scholar 

  28. Zheng C, Huang DR, Bergenbrant S, Sundblad A, Osterborg A, Bjorkholm M et al. Interleukin 6, tumour necrosis factor alpha, interleukin 1beta and interleukin 1 receptor antagonist promoter or coding gene polymorphisms in multiple myeloma. Br J Haematol 2000; 109: 39–45.

    Article  CAS  PubMed  Google Scholar 

  29. Prince HM, Mileshkin L, Roberts A, Ganju V, Underhill C, Catalano J et al. A multicenter phase II trial of thalidomide and celecoxib for patients with relapsed and refractory multiple myeloma. Clin Cancer Res 2005; 11: 5504–5514.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

This study was supported by the following grants: Kong Christian den Tiendes fond, the research fund at Herlev Hospital. Participants of NMSG. Christina Køgs Andersen.

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Authors and Affiliations

  1. Department of Oncology and Hematology, Roskilde County Hospital, Roskilde, Denmark

    A J Vangsted

  2. Department of Hematology, University of Copenhagen at Herlev, Herlev, Denmark

    A J Vangsted, T W Klausen & A O Gang

  3. National Research Center for the Working Environment, Copenhagen, Denmark

    W Ruminski & U Vogel

  4. Department of Hematology, University Hospital of Copenhagen at Rigshospitalet, Copenhagen, Denmark

    P Gimsing

  5. Department of Hematology, Aarhus University Hospital, Aarhus, Denmark

    N F Andersen & J L Nielsen

  6. Department of Hematology, Odense University Hospital, Odense, Denmark

    N Abildgaard & L M Knudsen

  7. Department of Hematology, Aalborg University Hospital, Aalborg, Denmark

    H Gregersen

  8. Department for Toxicology and Risk Assessment, National Food Institute, Technical University of Denmark, Copenhagen, Denmark

    U Vogel

  9. Institute for Science, Systems and Models, Roskilde University, Roskilde, Denmark

    U Vogel

Authors
  1. A J Vangsted
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  2. T W Klausen
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  3. W Ruminski
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  4. P Gimsing
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  5. N F Andersen
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  6. A O Gang
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  7. N Abildgaard
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  8. L M Knudsen
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  9. J L Nielsen
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  10. H Gregersen
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  11. U Vogel
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Corresponding author

Correspondence to A J Vangsted.

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Vangsted, A., Klausen, T., Ruminski, W. et al. The polymorphism IL-1β T-31C is associated with a longer overall survival in patients with multiple myeloma undergoing auto-SCT. Bone Marrow Transplant 43, 539–545 (2009). https://doi.org/10.1038/bmt.2008.351

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  • DOI: https://doi.org/10.1038/bmt.2008.351

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