SEARCH:   Advanced

Blood, 1 May 2007, Vol. 109, No. 9, pp. 3936-3944. Prepublished online as a Blood First Edition Paper on December 29, 2006; DOI 10.1182/blood-2006-05-022111. This Article Full Text Full Text (PDF) All Versions of this Article: blood-2006-05-022111v1 109/9/3936    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 CrossRef Citing Articles via Google Scholar Google Scholar Articles by Kuptsova, N. Articles by Ambrosone, C. B. Search for Related Content PubMed PubMed Citation Articles by Kuptsova, N. Articles by Ambrosone, C. B. Related Collections Neoplasia Clinical Trials and Observations Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  NEOPLASIA Polymorphisms in DNA repair genes and therapeutic outcomes of AML patients from SWOG clinical trials Nataliya Kuptsova1, Kenneth J. Kopecky2, John Godwin3, Jeanne Anderson4, Ashraful Hoque5, Cheryl L. Willman6, Marilyn L. Slovak7, and Christine B. Ambrosone1 1 Department of Cancer Prevention and Control, Roswell Park Cancer Institute, Buffalo, NY; 2 Southwest Oncology Group Statistical Center, Fred Hutchinson Cancer Research Center, Seattle, WA; 3 Southern Illinois University School of Medicine, Springfield, IL; 4 Katmai Oncology Group, Anchorage, AK; 5 University of Texas M. D. Anderson Cancer Center, Houston, TX; 6 University of New Mexico, Albuquerque, NM; 7 Department of Cytogenetics, City of Hope National Medical Center, Duarte, CA Repair of damage to DNA resulting from chemotherapy may influence drug toxicity and survival in response to treatment. We evaluated the role of polymorphisms in DNA repair genes APE1, XRCC1, ERCC1, XPD, and XRCC3 in predicting therapeutic outcomes of older adults with acute myeloid leukemia (AML) from 2 Southwest Oncology Group (SWOG) clinical trials. All patients received standard chemotherapy induction regimens. Using logistic and proportional hazards regression models, relationships between genotypes, haplotypes, and toxicities, response to induction therapy, and overall survival were evaluated. Patients with XPD Gln751C/Asp312G (‘D’) haplotype were more likely to have complete response (OR = 3.06; 95% CI, 1.44-6.70) and less likely to have resistant disease (OR = 0.32; 95%CI, 0.14-0.72) than patients with other haplotypes. ERCC1 polymorphisms were significantly associated with lung (P = .037) and metabolic (P = .041) toxicities, and patients with the XRCC3 241Met variant had reduced risk of liver toxicity (OR = 0.32; 95%CI, 0.11-0.95). Significant associations with other toxicities were also found for variant XPD genotypes/haplotypes. These data from clinical trials of older patients treated for AML indicate that variants in DNA repair pathways may have an impact on both outcomes of patients and toxicities associated with treatments. With validation of results in larger samples, these findings could lead to optimizing individual chemotherapy options. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

	Copyright © 2007 by American Society of Hematology         Online ISSN: 1528-0020