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Blood, 15 December 2008, Vol. 112, No. 13, pp. 4924-4934. Prepublished online as a Blood First Edition Paper on September 19, 2008; DOI 10.1182/blood-2008-02-140434. This Article Full Text Full Text (PDF) Supplemental Tables Supplemental Tables All Versions of this Article: blood-2008-02-140434v1 112/13/4924    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Johnson, D. C. Articles by Morgan, G. J. Search for Related Content PubMed PubMed Citation Articles by Johnson, D. C. Articles by Morgan, G. J. Related Collections Hemostasis, Thrombosis, and Vascular Biology Neoplasia Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY Genetic associations with thalidomide mediated venous thrombotic events in myeloma identified using targeted genotyping David C. Johnson1, Sophie Corthals2, Christine Ramos3, Antje Hoering4, Kim Cocks5, Nicholas J. Dickens1, Jeff Haessler4, Harmut Goldschmidt6, J. Anthony Child5, Sue E. Bell5, Graham Jackson7, Dalsu Baris8, S. Vincent Rajkumar9, Faith E. Davies1, Brian G. M. Durie10, John Crowley4, Pieter Sonneveld2, Brian Van Ness3, and Gareth J. Morgan1 1 Section of Haemato-Oncology, Institute of Cancer Research, London, United Kingdom; 2 Department of Hematology, Erasmus Medical Center, Rotterdam, The Netherlands; 3 Department of Genetics, Cell Biology, and Development, University of Minnesota, Minneapolis; 4 Cancer Research and Biostatistics (CRAB), Seattle, WA; 5 Clinical Trials Research Unit, University of Leeds, Leeds, United Kingdom; 6 Department of Internal Medicine, Division of Hematology/Oncology, Amyloidosis Clinic, University of Heidelberg, Heidelberg, Germany; 7 School of Laboratory and Clinical Sciences, University of Newcastle, Newcastle, United Kingdom; 8 Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD; 9 Department of Internal Medicine, Division of Hematology, Mayo Clinic, Rochester, MN; and 10 International Myeloma Foundation and Cedars Sinai Comprehensive Cancer Center, Los Angeles, CA A venous thromboembolism (VTE) with the subsequent risk of pulmonary embolism is a major concern in the treatment of patients with multiple myeloma with thalidomide. 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 microenvironment, and the endothelium. The clinical trials described in this paper have been registered as follows: MRC Myeloma IX: ISRCTN68454111 [controlled-trials.com] ; Hovon-50: NCT00028886 [ClinicalTrials.gov] ; and ECOG EA100: NCT00033332 [ClinicalTrials.gov] . CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: Genetic variants in XRRC5 may predict development of venous thrombotic events in myeloma patients on thalidomide Prerna Tewari, Elaine Kenny, Anthony Staines, Stephen Chanock, Paul Browne, and Mark Lawler Blood 2009 113: 5691-5692. [Full Text] [PDF] This article has been cited by other articles: A. Falanga and M. Marchetti Venous Thromboembolism in the Hematologic Malignancies J. Clin. Oncol., October 10, 2009; 27(29): 4848 - 4857. [Abstract] [Full Text] [PDF] P. Tewari, E. Kenny, A. Staines, S. Chanock, P. Browne, and M. Lawler Genetic variants in XRRC5 may predict development of venous thrombotic events in myeloma patients on thalidomide Blood, May 28, 2009; 113(22): 5691 - 5692. [Full Text] [PDF]

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