谷胱甘肽巯基转移酶基因型与儿童急性淋巴细胞白血病化疗相关毒副反应的关系

Association between the Glutathione S-transferases(GST) genotypes and chemotherapy related adverse effects in children with acute lymphoblastic leukaemia

目的探讨谷胱甘肽巯基转移酶(GST)基因型与儿童急性淋巴细胞白血病(ALL)化疗相关毒副反应的关系。方法随机抽取2003年1月-2008年12月间在复旦大学附属儿科医院血液肿瘤科接受化疗的80例ALL患儿,应用PCR方法进行GSTT1和GSTM1基因型检测,分析GST基因型与诱导化疗和大剂量甲氨蝶呤(HD-MTX)化疗相关毒副反应的关系。结果检出GSTT1缺失基因型11例(13.8%),GSTM1缺失基因型27例(33.8%)。诱导化疗期中高危组GSTM1缺失基因型患儿肝损害发生率显著高于GSTM1非缺失基因型患儿(53.3%vs10.3%,P=0.011)。GSTT1和GSTM1基因型与标危组诱导化疗和HD-MTX化疗相关肝损害的发生无关,与化疗相关感染的发生也无关。结论 GSTM1基因型与接受较强烈诱导化疗的ALL中高危组患儿化疗相关肝损害的发生相关。

Objective To evaluate the association between the GST genotypes and chemotherapy related adverse effect in children with acute lymphoblastic leukaemia（ALL）.Methods The genotypes of GSTT1 and GSTM1 were detected by polymerase chain reaction（PCR）-based methods in the patients with ALL treated at Division of Hematology and Oncology in children＇s hospital of Fudan University between Jan,2003 and Dec,2008.The association between the GST genotypes and the adverse effect in induction and high-dose methotrexate（HDMTX） administration was investigated.Results Totally eighty patients（48 boys and 32 girls;median age 4.9 years,range 1-15.3 years） were involved in this study.The GSTT1（-） and GSTM1（-） genotypes were detected in 11 cases（13.8%） and 27 cases（33.8%）,respectively.In induction chemotherapy,there was a significantly increased incidence of hepatotoxicity in mediate/high risk patients with the GSTM1（-） genotype compared with the GSTM1（＋） genotype（53.3% vs 10.3%,P=0.011）.GSTT1 and GSTM1 genotypes did not show any association with hepatotoxicity in standard risk patients neither in induction chemotherapy nor in HDMTX administration.Chemotherapy related infection seemed not to be associated with GSTT1 and GSTM1 genotypes in this report.Conclusion GSTM1 genotype is associated with chemotherapy related hepatotoxicity in mediate/high risk ALL patients who receive more intensive induction chemotherapy.