Combined interaction of multi-locus genetic polymorphisms in cytarabine arabinoside metabolic pathway on clinical outcomes in adult acute myeloid leukaemia (AML) patients

被引：24
作者：
Kim, Kyung Im [1 ]
Huh, Ik-Soo [2 ]
Kim, In-Wha [1 ,3 ]
Park, Taesung [2 ]
Ahn, Kwang-Sung [4 ]
Yoon, Sung-Soo [4 ,5 ,6 ]
Yoon, Jeong-Hyun [7 ]
Oh, Jung Mi [1 ,3 ]
机构：
[1] Seoul Natl Univ, Coll Pharm, Seoul 151742, South Korea
[2] Seoul Natl Univ, Dept Stat, Seoul 151742, South Korea
[3] Seoul Natl Univ, Pharmaceut Sci Res Inst, Seoul 151742, South Korea
[4] Seoul Natl Univ Hosp, Clin Res Inst, Seoul 110744, South Korea
[5] Seoul Natl Univ, Coll Med, Dept Internal Med, Seoul 151742, South Korea
[6] Seoul Natl Univ, Canc Res Inst, Seoul 151742, South Korea
[7] Pusan Natl Univ, Coll Pharm, Pusan, South Korea
来源：
EUROPEAN JOURNAL OF CANCER | 2013年 / 49卷 / 02期
关键词：
Acute myeloid leukaemia; Single nucleotide polymorphism; SNP-SNP interaction; Cytarabine; Response; Ethnicity; SINGLE-NUCLEOTIDE POLYMORPHISM; ARA-C SENSITIVITY; DEOXYCYTIDINE KINASE; CYTOSINE-ARABINOSIDE; 1-BETA-D-ARABINOFURANOSYLCYTOSINE; THYMIDINE; EXPRESSION; SURVIVAL; THERAPY; CELLS;
D O I：
10.1016/j.ejca.2012.07.022
中图分类号：
R73 [肿瘤学];
学科分类号：
100214 ;
摘要：
Cytarabine arabinoside (ara-C) is the key agent for treating acute myeloid leukaemia (AML). Here, we genotyped 139 single nucleotide polymorphisms (SNPs) within the araC transport and metabolic pathway using the Illumina Golden Gate Assay in 97 patients with previously non-treated de novo AML other than M3. DCK rs4694362 (CC genotype) was a significant poor prognostic factor for overall survival (OS) (hazard ratio [HR], 33.202 [95% confidence interval (CI), 4.937-223.273], P < 0.0001, P-Bonferroni = 0.017). SLC29A1 rs3734703 (AA or AC genotype) in combination with TYMS rs2612100 (AA genotype) was significantly associated with shorter relapse free survival (RFS) (HR, 17.630 [95% CI, 4.829-64.369], P < 0.0001, P-Bonferroni = 0.021). These SNPs showed moderate or large inter-ethnic divergence in allele frequencies from African or Caucasian populations. The results of our study suggest that a single SNP and SNP-SNP interactions may help to predict the drug response and provide a guide in developing individualised chemotherapy for AML patients receiving ara-C based chemotherapy. (C) 2012 Elsevier Ltd. All rights reserved.
引用
收藏
页码：403 / 410
页数：8
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