title: Polymorphisms of ERCC1 genotype associated with response to imatinib therapy in chronic phase chronic myeloid leukemia.
abstract: DNA repair machinery may contribute to the mechanism of the action in imatinib. We examined the association between the single nucleotide polymorphism (SNP) markers involved in the DNA repair enzyme pathway (ERCC1/2/4/5, XRCC1/2/4/5) and the clinical outcomes following an imatinib therapy in chronic phase chronic myeloid leukemia (CML) patients. A total of 169 Korean patients were included. Of the 19 SNPs from these patients, those with the TT genotype of ERCC1 (rs11615) showed a higher probability of achieving major cytogenetic response [P = 0.002, HR 5.14 (95 % CI 1.83-14.43)], complete cytogenetic response [P = 0.012, HR 3.47 (95 % CI 1.31-9.17)], and major molecular response [P = 0.001, HR 5.71 (95 % CI 2.13-15.30)] than those with CC or CT genotypes. This suggests that SNP markers on ERCC1 may predict the response to imatinib therapy, which proposes the potential involvement of the DNA repair machinery in the mechanism of imatinib action in chronic phase CML.
authors: Division of Hematology/Medical Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors: Jee Hyun
authors: JH
authors: Kong
authors: Yeung-Chul
authors: YC
authors: Mun
authors: Seonwoo
authors: S
authors: Kim
authors: Hang Seok
authors: HS
authors: Choi
authors: Yeo-Kyeoung
authors: YK
authors: Kim
authors: Hyeoung-Joon
authors: HJ
authors: Kim
authors: Joon Ho
authors: JH
authors: Moon
authors: Sang Kyun
authors: SK
authors: Sohn
authors: Sung-Hyun
authors: SH
authors: Kim
authors: Chul Won
authors: CW
authors: Jung
authors: Dong Hwan
authors: DH
authors: Dennis Kim
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001549:Benzamides; D004268:DNA-Binding Proteins / Q000235:genetics*; D004720:Endonucleases / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D000068877:Imatinib Mesylate; D015466:Leukemia, Myeloid, Chronic-Phase / Q000188:drug therapy* / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D010879:Piperazines / Q000008:administration & dosage / Q000627:therapeutic use*; D020641:Polymorphism, Single Nucleotide; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D011743:Pyrimidines / Q000008:administration & dosage / Q000627:therapeutic use*; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D001549:Benzamides; D004268:DNA-Binding Proteins; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D000068877:Imatinib Mesylate; C071447:ERCC1 protein, human; D004720:Endonucleases