TY - JOUR
T1 - Polymorphisms in DNA repair genes and therapeutic outcomes of AML patients from SWOG clinical trials
AU - Kuptsova, Nataliya
AU - Kopecky, Kenneth J.
AU - Godwin, John
AU - Anderson, Jeanne
AU - Hoque, Ashraful
AU - Willman, Cheryl L.
AU - Slovak, Marilyn L.
AU - Ambrosone, Christine B.
PY - 2007/5/1
Y1 - 2007/5/1
N2 - Repair of damage to DNA resulting from chemotherapy may influence drug toxicity and survival in response to treatment. We evaluated the role of polymorphisms inDNA 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 signifi-cantly 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.
AB - Repair of damage to DNA resulting from chemotherapy may influence drug toxicity and survival in response to treatment. We evaluated the role of polymorphisms inDNA 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 signifi-cantly 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.
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U2 - 10.1182/blood-2006-05-022111
DO - 10.1182/blood-2006-05-022111
M3 - Article
C2 - 17197435
AN - SCOPUS:34247374739
SN - 0006-4971
VL - 109
SP - 3936
EP - 3944
JO - Blood
JF - Blood
IS - 9
ER -