GSTT1、GSTM1基因多态性与儿童急性淋巴细胞白血病早期治疗反应及化疗不良反应的关系

Effects of glutathione S-transferase(GSTT1 and GSTM1) genes polymorphisms on early treatment response and chemotherapy toxicities of childhood acute lymphoblastic leukemia

目的:研究谷胱甘肽硫转移酶(GSTs)家族中GSTT1、GSTM1基因多态性与儿童急性淋巴细胞白血病(ALL)早期治疗反应和化疗不良反应的关系。方法:筛选ALL患者98例,采用多重PCR技术分析GSTT1、GSTM1基因型,比较不同基因型患者早期治疗反应和发生化疗毒副作用的差异。结果:GSTT1基因缺失型患者早期治疗反应较GSTT1基因非缺失型患者好(OR=3.35,95%CI:1.05～10.73,P=0.041),GSTT1和GSTM1基因双非缺失型患者发生早期治疗反应差的风险明显高于GSTT1和GSTM1任一基因缺失型及双缺失型(OR=5.73,95%CI:1.73～18.95,P=0.004)。GSTM1基因缺失型患者发生口腔黏膜炎、肝功能异常及感染的风险高于GSTM1基因非缺失型患者(P<0.05),GSTT1和GSTM1基因双缺失型患者发生肝功能异常及感染的风险明显高于两基因非双缺失型患者(P<0.05)。结论:GSTT1和GSTM1基因型与ALL患者早期治疗反应及化疗不良反应发生率相关,GSTT1和GSTM1基因型有助于指导ALL患者个体化治疗方案的制定。

Objective：To investigate the impact of GSTrl and GSTM1 genotypes on early treatment response and chemotherapy toxicities of childhood acute lymphoblastic leukemia （ALL）. Methods： GSTT1 and GSTM1 genotypes were analyzed with PCR in 98 ALL patients. The early treatment response and chemotherapy toxicities were compared between groups with or without GSTT1 and GSTM1 genes. Results：Patients without GSTT1 gene had better early treatment response than patients with GSIT1 gene （OR= 3.35,95%CI： 1.05-10.73 ,P=0.041）. The risk of poor early treatment response in patients with GSTT1 and GSTM1 double present was much higher than that in patients with GSTT1 null or GSTM1 null （0R=5.73,95%CI： 1.73-18.95,P=0.004）. The risk of oral mucositis, heptatoxicity and infection in patients with GSTM1 null was higher than that in patients with GSTM1 present （P 〈 0.05）. Patients without GSTT1 and GSTM1 genes experienced more heptatoxicity and infection than patients with GSTI＇I and GSTM1 genes （P 〈 0.05）. Conclusion：GSTT1 and GSTM1 genotypes were apparently related to early treatment response and chemotherapy toxicity of patients with ALL. GSTT1 and GSTM1 genotypes might be useful in selecting appropriate chemotherapy regimens for patients with ALL.