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Blood, 15 December 2004, Vol. 104, No. 13, pp. 3872-3877. Prepublished online as a Blood First Edition Paper on August 31, 2004; DOI 10.1182/blood-2004-06-2161. This Article Full Text (PDF) All Versions of this Article: 2004-06-2161v1 104/13/3872    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 Allan, J. M Articles by Wild, C. P Search for Related Content PubMed PubMed Citation Articles by Allan, J. M Articles by Wild, C. P Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted June 14, 2004 Accepted August 6, 2004 Genetic variation in XPD predicts treatment outcome and risk of acute myeloid leukemia following chemotherapy James M Allan*, Alexandra G Smith, Keith Wheatley, Robert K Hills, Lois B Travis, Deirdre A Hill, David M Swirsky, Gareth J Morgan, and Christopher P Wild Epidemiology and Genetics Unit, Department of Biology, University of York, York, United Kingdom Epidemiology and Genetics Unit, Department of Health Sciences, University of York, York, United Kingdom Birmingham Clinical Trials Unit, University of Birmingham, Birmingham, United Kingdom Division of Cancer Epidemiology and Genetics, Department of Health and Human Services, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA Haematological Malignancy Diagnostic Service, Leeds General Infirmary, Leeds, United Kingdom Institute of Cancer Research, Royal Marsden Hospital, Surrey, United Kingdom Molecular Epidemiology Unit, School of Medicine, University of Leeds, Leeds, United Kingdom * Corresponding author; email: jim.allan{at}egu.york.ac.uk. The xeroderma pigmentosum group D (XPD) gene encodes a DNA helicase that functions in nucleotide excision repair of chemotherapy-induced DNA damage, the efficiency of which is predicted to be affected by a lysine to glutamine variant at codon 751. We hypothesized that this constitutive genetic variant may modify clinical response to chemotherapy, and have examined its impact on outcome following chemotherapy for acute myeloid leukemia (AML) in 341 elderly patients entered into the United Kindgom Medical Research Council AML 11 trial, and on the risk of developing chemotherapy-related AML. Among subjects treated for AML, disease-free survival at one year was 44% for lysine homozygotes, compared to 36% for heterozygotes and 16% for glutamine homozygotes (hazard ratio (HR) 1.30, 95% confidence interval (CI) 1.01-1.70, p=0.04). Similarly, overall survival at one year was 38% for lysine homozygotes, 35% for heterozygotes and 23% for glutamine homozygotes (HR 1.18, 95% CI 0.99-1.41, p=0.07). Furthermore, homozygosity for the XPD codon 751 glutamine variant was associated with a significantly increased risk of developing AML after chemotherapy (odds ratio 2.22 for Gln/Gln vs Lys/Lys, 95% CI 1.04-4.74). These data suggest that the XPD codon 751 glutamine variant protects against myeloid cell death after chemotherapy. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: R. Gao, D. K. Price, T. Sissung, E. Reed, and W. D. Figg Ethnic disparities in Americans of European descent versus Americans of African descent related to polymorphic ERCC1, ERCC2, XRCC1, and PARP1 Mol. Cancer Ther., May 1, 2008; 7(5): 1246 - 1250. [Abstract] [Full Text] [PDF] N. Kuptsova, K. J. Kopecky, J. Godwin, J. Anderson, A. Hoque, C. L. Willman, M. L. 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Jarvis, J. M. Cheverud, M. Minn, V. Mathews, M. A. Bogue, M. A. Province, H. L. McLeod, et al. Identification of candidate alkylator-induced cancer susceptibility genes by whole genome scanning in mice. Cancer Res., May 15, 2006; 66(10): 5029 - 5038. [Abstract] [Full Text] [PDF] L. B. Travis, C. S. Rabkin, L. M. Brown, J. M. Allan, B. P. Alter, C. B. Ambrosone, C. B. Begg, N. Caporaso, S. Chanock, A. DeMichele, et al. Cancer Survivorship--Genetic Susceptibility and Second Primary Cancers: Research Strategies and Recommendations J Natl Cancer Inst, January 4, 2006; 98(1): 15 - 25. [Abstract] [Full Text] [PDF] P. A. Mehta, T. A. Alonzo, R. B. Gerbing, J. S. Elliott, T. A. Wilke, R. J. Kennedy, J. A. Ross, J. P. Perentesis, B. J. Lange, and S. M. Davies XPD Lys751Gln polymorphism in the etiology and outcome of childhood acute myeloid leukemia: a Children's Oncology Group report Blood, January 1, 2006; 107(1): 39 - 45. [Abstract] [Full Text] [PDF]

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