Cancer Genetics

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Polymorphisms in the genes ERCC2, XRCC3 and CD3EAP influence treatment outcome in multiple myeloma patients undergoing autologous bone marrow transplantation

  1. Annette Vangsted1,†,*,
  2. Peter Gimsing2,
  3. Tobias W. Klausen1,
  4. Bjørn A. Nexø3,
  5. Håkan Wallin4,
  6. Pernille Andersen5,
  7. Peter Hokland6,
  8. Søren T. Lillevang7,
  9. Ulla Vogel4

Article first published online: 27 NOV 2006

DOI: 10.1002/ijc.22411

Issue

International Journal of Cancer

International Journal of Cancer

Volume 120, Issue 5, pages 1036–1045, 1 March 2007

Additional Information

How to Cite

Vangsted, A., Gimsing, P., Klausen, T. W., Nexø, B. A., Wallin, H., Andersen, P., Hokland, P., Lillevang, S. T. and Vogel, U. (2007), Polymorphisms in the genes ERCC2, XRCC3 and CD3EAP influence treatment outcome in multiple myeloma patients undergoing autologous bone marrow transplantation. Int. J. Cancer, 120: 1036–1045. doi: 10.1002/ijc.22411

Author Information

  1. 1

    Department of Haematology, Herlev University Hospital of Copenhagen, DK-2730 Herlev, Denmark

  2. 2

    Department of Haematology, Rigshospitalet, University Hospital of Copenhagen, DK-2100 Copenhagen, Denmark

  3. 3

    Institute of Human Genetics, University of Aarhus, DK-8000 Aarhus C, Denmark

  4. 4

    National Institute of Occupational Health, DK-2100 Copenhagen, Denmark

  5. 5

    Department of Clinical Immunology, Rigshospitalet, University Hospital of Copenhagen, DK-2100 Copenhagen, Denmark

  6. 6

    Department of Haematology, University Hospital of Aarhus, DK-8000 Aarhus, Denmark

  7. 7

    Department of Clinical Immunology, University Hospital of Odense, DK-5270 Odense, Denmark

  1. †

    Fax: 45-44532518.

*Department of Haematology, Copenhagen University of Herlev, Herlev Ringvej 75, 2730 Herlev, Denmark

Publication History

  1. Issue published online: 19 JAN 2007
  2. Article first published online: 27 NOV 2006
  3. Manuscript Accepted: 12 SEP 2006
  4. Manuscript Received: 20 APR 2006

Funded by

  • Købmand Sven Hansen and Hustru Ina Hansen Fund
  • Dir. Leo Nielsen's and Hustru Margrethe Nielsen's Medical Research Fund
  • Folketingsmand Jens Christensen and Hustru Korna Christensen's Fund
  • The Danish Medical Association Research Fund/Mimi
  • Victor Larsen's Fund

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Keywords:

  • chemotherapy;
  • DNA repair genes;
  • polymorphism;
  • multiple myeloma;
  • treatment outcome

Abstract

Individual variations in the ability to cope with DNA damage by DNA repair may be essential for the response to chemotherapy, since cancer cells from patients with an effective DNA repair may survive treatment. We have studied the effect on time to treatment failure (TTF) and overall survival (OS) of polymorphism in the DNA repair genes ERCC1, ERCC2 and XRCC3, and in the apoptotic genes PPP1R13L and CD3EAP in 348 patients with multiple myeloma undergoing autologous bone marrow transplantation. Carriers of the variant C-allele of ERCC2 K751Q, the variant T-allele of XRCC3 T241M and the variant A-allele of CD3EAP G-21A had a 1.3-fold, 1.8-fold and 1.9-fold longer TTF, respectively, than homozygous wild type carriers (p = 0.006, p = 0.004, p < 0.001). The polymorphism CD3EAP G-21A also had significant effect on OS (p < 0.045). The polymorphism ERCC2 K751Q may to be related to sex, since the prolonged TTF was only seen in women (p = 0.001). Carriers of the combination of variant alleles of ERCC2 K751Q and XRCC3 T241M had 2.8-fold longer TTF (p = 0.0002). This indicates that suboptimal repair of both DNA mechanisms favors prolonged TTF and that polymorphism in ERCC2, XRCC3 and CD3EAP predicts the outcome for patients treated with autologous stem cell transplantation. © 2006 Wiley-Liss, Inc.

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