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Prepublished online as a Blood First Edition Paper on June 5, 2003; DOI 10.1182/blood-2003-02-0444. This Article Full Text (PDF) All Versions of this Article: 2003-02-0444v1 102/7/2345    most recent Alert me when this article is cited Alert me if a correction is posted 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 Dasgupta, R. K Articles by Morgan, G. J Search for Related Content PubMed PubMed Citation Articles by Dasgupta, R. K Articles by Morgan, G. J Social Bookmarking                   What's this? Submitted February 10, 2003 Accepted May 5, 2003 Polymorphic variation in GSTP1 modulates outcome following therapy for multiple myeloma Ranjit K Dasgupta, Peter J Adamson, Faith E Davies, Sara Rollinson, Philippa L Roddam, A J Ashcroft, Ann M Dring, James A Fenton, J A Child, James M Allan, and Gareth J Morgan* Academic Unit of Haematology and Oncology, University of Leeds, Leeds, West Yorkshire, United Kingdom Epidemiology and Genetics Unit, University of Leeds, Leeds, West Yorkshire, United Kingdom * Corresponding author; email: garethm{at}lrf.leeds.ac.uk. Glutathione S-transferase P1 (GSTP1) is a phase II drug metabolism enzyme involved in the metabolism and detoxification of a range of chemotherapeutic agents. A single nucleotide polymorphism (Ile105Val) results in a variant enzyme with lower thermal stability and altered catalytic activity. We hypothesized that patients with the less stable variant have a decreased ability to detoxify chemotherapeutic substrates including melphalan, and have an altered outcome following treatment for multiple myeloma. We have genotyped 222 patients entered into the MRC myeloma VII trial (comparing standard dose chemotherapy to high dose therapy) for the GSTP1 codon 105 polymorphism. In the standard dose arm (n=101)patients with the variant allele (105Val) had an improved progression free survival (compared to 105Ile homozygotes adjusted hazard ratios for PFS were 0.55 for heterozygotes and 0.52 for 105Val homozygotes, p for trend = 0.04). This was supported by a trend to improved overall survival, greater likelihood of entering plateau and shorter time to reach plateau in patients with the 105Val allele. No difference in outcome between genotype was found for patients treated with high dose therapy (n=121). However, the progression-free survival advantage seen with the high dose arm was only seen in patients homozygous for 105Ile (p=0.008). CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: R. S. Huang, S. Duan, E. O. Kistner, W. K. Bleibel, S. M. Delaney, D. L. Fackenthal, S. Das, and M. E. Dolan Genetic Variants Contributing to Daunorubicin-Induced Cytotoxicity Cancer Res., May 1, 2008; 68(9): 3161 - 3168. [Abstract] [Full Text] [PDF] J. Oldenburg, S. M. Kraggerud, M. Cvancarova, R. A. Lothe, and S. D. Fossa Cisplatin-Induced Long-Term Hearing Impairment Is Associated With Specific Glutathione S-Transferase Genotypes in Testicular Cancer Survivors J. Clin. Oncol., February 20, 2007; 25(6): 708 - 714. [Abstract] [Full Text] [PDF] C. Schilthuizen, A. Broyl, B. van der Holt, Y. de Knegt, H. Lokhorst, and P. Sonneveld Influence of genetic polymorphisms in CYP3A4, CYP3A5, GSTP1, GSTM1, GSTT1 and MDR1 genes on survival and therapy-related toxicity in multiple myeloma Haematologica, February 1, 2007; 92(2): 277 - 278. [Abstract] [Full Text] [PDF] M. Wrensch, A. McMillan, J. Wiencke, J. Wiemels, K. Kelsey, J. Patoka, H. Jones, V. Carlton, R. Miike, J. Sison, et al. Nonsynonymous Coding Single-Nucleotide Polymorphisms Spanning the Genome in Relation to Glioblastoma Survival and Age at Diagnosis Clin. Cancer Res., January 1, 2007; 13(1): 197 - 205. [Abstract] [Full Text] [PDF] J.-M. Lee, M.-T. Wu, Y.-C. Lee, S.-Y. Yang, J.-S. Chen, H.-H. Hsu, P.-M. Huang, S.-W. Kuo, C.-J. Lee, and C.-J. Chen Association of GSTP1 Polymorphism and Survival for Esophageal Cancer Clin. Cancer Res., July 1, 2005; 11(13): 4749 - 4753. [Abstract] [Full Text] [PDF] S. Hohaus, A. Di Ruscio, A. Di Febo, G. Massini, F. D'Alo', F. Guidi, G. Mansueto, M. T. Voso, and G. Leone Glutathione S-transferase P1 Genotype and Prognosis in Hodgkin's Lymphoma Clin. Cancer Res., March 15, 2005; 11(6): 2175 - 2179. [Abstract] [Full Text] [PDF] M. R. Spitz, X. Wu, and G. Mills Integrative Epidemiology: From Risk Assessment to Outcome Prediction J. Clin. Oncol., January 10, 2005; 23(2): 267 - 275. [Abstract] [Full Text] [PDF]

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