谷胱甘肽S-转移酶（GSTT1和GSTM1）基因多态性对急性髓系白血病治疗疗效及预后的影响

[The effects of glutathione S-transferase (GSTT1 and GSTM1) genes polymorphisms on treatment efficacy and prognosis of acute myeloid leukemia].

作者信息

Zhang Yue, Yang Lin, Li Rui, Zhang Li, Zhang Mei-rong, Xiao Zhi-jian

机构信息

Institute of Hematology, Chinese Academe of Medical Sciences & Peking Union Medical College, Tianjin 300020, China.

出版信息

Zhonghua Nei Ke Za Zhi. 2006 Mar;45(3):213-6.

PMID:16624155

Abstract

OBJECTIVE

To investigate the impact of GSTT1 and GSTM1 genotypes on response, drug side effects and prognosis of acute myeloid leukemia (AML).

METHODS

GSTT1 and GSTM1 genotypes were analysed in 180 AML patients with PCR. Complete remission (CR) rate, drug side-effects, overall survival, relapse-free survival and relapse rate were compared in groups with or without GSTT1 and GSTM1 genes.

RESULTS

(1) The CR rate (96.9%) in GSTT1 and GSTM1 genes double-present patients was significantly higher than that in patients of GSTT1 null or GSTM1 null (CR rate 78.0%) (P = 0.013). The risk of failure to achieve CR in patients with GSTT1 null/GSTM1 null is 8.736 times higher than that in patients with GSTT1 and GSTM1 genes double-present (odds ratio OR was 8.736, 95% CI was 1.146 - 66.574). The CR rate (88.4%) in GSTT1 present patients was also significantly higher than that in patients of GSTT1 null (CR rate 74.7%) (P = 0.021, OR = 2.572, 95% CI 1.136 - 5.826). (2) There was no significant relationship between GSTT1/GSTM1 genotypes and the lasting time of neutrophilic granulocyte (ANC) < 0.5 x 10(9)/L and PLT < 20 x 10(9)/L. The risk of ALT abnormality in patients with GSTM1 null is 2.593 times higher than that in patients with GSTM1 present (P = 0.016, 95% CI 1.176 - 5.717). (3) Overall survival and relapse-free survival of GSTT1 and GSTM1 double-present patients were significantly better than those in patients of GSTT1 null/GSTM1 null (mean overall survival was 68.4 months vs 38.5 months, P = 0.028, and mean relapse-free survival was 73.5 months vs 34.9 months, P = 0.014, respectively). Relapse-free survival in GSTT1 null patients was significantly shorter than that in patients with GSTT1 present (26.7 months vs 64.3 months, P = 0.038), but there was no significant difference of overall survival between the two groups. The relapse rate of double-present patients was significantly lower than that of GSTT1 null/GSTM1 null patients (13.3% vs 35.6%, P = 0.019).

CONCLUSION

GSTT1 and GSTM1 genotypes were apparently related with response, drug side effects and prognosis of patients with AML. GSTT1 and GSTM1 genotype might be useful in selecting appropriate chemotherapy regimens for patients with AML.

摘要

目的

探讨谷胱甘肽S-转移酶T1（GSTT1）和谷胱甘肽S-转移酶M1（GSTM1）基因多态性对急性髓系白血病（AML）患者化疗疗效、药物不良反应及预后的影响。

方法

采用聚合酶链反应（PCR）技术检测180例AML患者的GSTT1和GSTM1基因多态性，比较GSTT1和GSTM1基因存在或缺失患者的完全缓解（CR）率、药物不良反应、总生存、无复发生存及复发率。

结果

（1）GSTT1和GSTM1基因均存在患者的CR率（96.9%）显著高于GSTT1或GSTM1基因缺失患者（CR率78.0%）（P = 0.013）。GSTT1和GSTM1基因均缺失患者未达CR的风险是GSTT1和GSTM1基因均存在患者的8.736倍（比值比OR为8.736，95%可信区间CI为1.146 - 66.574）。GSTT1基因存在患者的CR率（88.4%）也显著高于GSTT1基因缺失患者（CR率74.7%）（P = 0.021，OR = 2.572，95%CI 1.136 - 5.826）。（2）GSTT1/GSTM1基因多态性与中性粒细胞绝对值（ANC）<0.5×10⁹/L及血小板计数（PLT）<20×10⁹/L的持续时间无显著相关性。GSTM1基因缺失患者谷丙转氨酶（ALT）异常的风险是GSTM1基因存在患者的2.593倍（P = 0.016，95%CI 1.176 - 5.717）。（3）GSTT1和GSTM1基因均存在患者的总生存及无复发生存均显著优于GSTT1和GSTM1基因均缺失患者（平均总生存时间分别为68.4个月和38.5个月，P = 0.028；平均无复发生存时间分别为73.5个月和34.9个月，P = 0.014）。GSTT1基因缺失患者的无复发生存时间显著短于GSTT1基因存在患者（26.7个月对64.3个月，P = 0.038），但两组总生存无显著差异。GSTT1和GSTM1基因均存在患者的复发率显著低于GSTT1和GSTM1基因均缺失患者（13.3%对35.6%，P = 0.019）。