Genetic associations with thalidomide mediated venous thrombotic events in myeloma identified using targeted genotyping

David C. Johnson, Sophie Corthals, Christine Ramos, Antje Hoering, Kim Cocks, Nicholas J. Dickens, Jeff Haessler, Harmut Goldschmidt, J. Anthony Child, Sue E. Bell, Graham Jackson, Dalsu Baris, S. Vincent Rajkumar, Faith E. Davies, Brian G.M. Durie, John Crowley, Pieter Sonneveld, Brian Van Ness, Gareth J. Morgan

Research output: Contribution to journalArticlepeer-review

58 Scopus citations


A venous thromboembolism (VTE) with the subsequent risk of pulmonary embolism isamajor concernin the treatment of patients with multiple myeloma with tha-lidomide. The susceptibility to developing a VTE in response to thalidomide therapy is likely to be influenced by both genetic and environmental factors. To test genetic variation associated with treatment related VTE in patient peripheral blood DNA, we used a custom-built molecular inversion probe (MIP) - based single nucleotide polymorphism (SNP) chip containing 3404 SNPs. SNPs on the chip were selected in "functional regions" within 964 genes spanning 67 molecular pathways thought to be involved in the pathogenesis, treatment response, and side effects associated with myeloma therapy. Patients and controls were taken from 3 large clinical trials: Medical Research Council (MRC) Myeloma IX, Hovon-50, and Eastern Cooperative Oncology Group (ECOG) EA100, which compared conventional treatments with thalidomide in patients with myeloma. Our analysis showed that the set of SNPs associated with thalidomide-related VTE were enriched in genes and pathways important in drug transport/metabolism, DNA repair, and cytokine balance. The effects of the SNPs associated with thalidomide-related VTE may be functional at the level of the tumor cell, the tumor-related micro-environment, and the endothelium. The clinical trials described in this paper have been registered as follows: MRC Myeloma IX: ISRCTN68454111; Hovon-50: NCT00028886; and ECOG EA100: NCT00033332.

Original languageEnglish (US)
Pages (from-to)4924-4934
Number of pages11
Issue number13
StatePublished - Dec 15 2008

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology


Dive into the research topics of 'Genetic associations with thalidomide mediated venous thrombotic events in myeloma identified using targeted genotyping'. Together they form a unique fingerprint.

Cite this