【摘要】 目的:观察临床应用含伊立替康方案化疗的恶性肿瘤患者不良反应与UGT1A1*28及UGT1A1*6基因多态性的相关性。方法:收集107例以伊立替康为基础化疗的恶性肿瘤患者,抽取患者外周血并提取基因组DNA,进行UGT1A1*6和UGT1A1*28多态性分型,分析比较不同基因型之间严重不良反应的发生差异。结果:UGT1A1*28突变者3/4级血小板减少(P=0.09)和腹泻(P=0.041)发生率明显增加,3/4级中性粒细胞及血红蛋白减少未见明显差异(P>0.05)。UGT1A1*6多态性与3/4级血液学总毒性(P=0.036)及中性粒细胞减少(P=0.034)相关,但对血红蛋白及血小板无明显影响(P>0.05),并不增加严重腹泻的发生风险(P=0.848)。UGT1A1*6/*28、*28/*28或*6/*6者无论血液学毒性还是迟发型腹泻的风险均明显增加。结论:UGT1A1多态性与伊立替康化疗后3/4级血液学毒性及迟发性腹泻的发生相关。更多还原

【Abstract】 Objective:To study the differences in toxicity among UGT1A1*28and UGT1A1*6gene polymorphisms patients receiving irinotecan chemotherapy.Methods:A total of 107 Chinese patients with malignant tumor who received irinotecan based chemotherapy were enrolled.The patients’ peripheral blood samples were collected and the genomic DNA extracted,then the patients were assigned into two groups according to genotype UGT1A1*6and UGT1A1*28.The differences of serious adverse reactions between different genotypes were compared.Results:The incidence of grade 3/4thrombocytopenia(P=0.09)and delayed diarrhea(P=0.041)in the patients carrying UGT1A1*28was higher than in those of wild genotype,while neutropenia showed no significant difference(P>0.05).UGT1A1*6polymorphism was associated with the general toxicity of hematology(P=0.036)and grade 3/4neutropenia(P=0.034).It seems that there was no significant effect on hemoglobin and platelet(P>0.05),and does not increase the risk of severe diarrhea(P =0.848).Comprehensive analysis indicated that UGT1A1 mutations(UGT1A1*6/*28,*28/*28or*6/*6)significantly increased the risk of both hematological toxicity and delayed diarrhea.Conclusion:The UGT1A1 polymorphisms significantly associates with irinotecan induced hematologic toxicity and delayed diarrhea.更多还原