UDP-葡萄糖醛酸转移酶1A1基因多态性及其与伊立替康化疗不良反应的关系

目的 研究中国进展期胃肠道肿瘤患者UDP-葡萄糖醛酸转移酶1A1（UGT1A1）的基因多态性及其与伊立替康化疗不良反应的发生率和严重程度的关系.方法 利用聚合酶链反应-连接酶检测反应（PCR-LDR）等方法对202例进展期胃肠道肿瘤患者进行UGT1A1基因多态性检测.所有患者均采用含伊立替康方案化疗,观察并记录化疗中出现的不良反应情况,比较不同基因型患者使用伊立替康后不良反应发生率的差异.结果 202例患者中UGT1A1野生型TA6/TA6 156例（77.2％）；杂合突变型TA6/TA744例（21.8％）,纯合突变型TA7/TA7 2例（1.0％）.3～4度不良反应的情况：腹泻27例（13.4％）、白细胞减少19例（9.4％）,TA6/TA6与TA6/TA7基因型患者出现3级以上腹泻、白细胞减少与1～2级之间差异无统计学意义（P＞0.05）.TA7/TA7基因型患者出现3级以上腹泻100％,白细胞减少50％.结论 用伊立替康化疗前行UGT1A1基因多态性检测可以筛查高危人群,预测伊立替康的严重不良反应,以指导临床用药.

Relationship between UGT1A1 gene polymorphisms and toxicity of irinotecan

Objective To study the relationship between the UDP-glucuronic acid transferrase-1 A1 （UGT1A1）gene polymorphisms and the incidence and severity of toxicity of Irinotecan in Chinese patients with advanced gastrointestinal tumors.Methods Polymorphisms of UGT1A1 were detected by polymerase chain reaction-ligation detection reaction from 202 patients with advanced gastrointestinal tumors treated with irinotecan.The adverse events were recorded and the difference in adverse events among various genotypes was compared.Results Of all cases,the frequencies of the wildtype TA6/TA6,heterozygote mutant TA6/TA7 and homozygote mutant TA7/TA7 genotypes were 77.2％ （n=156）,21.8％ （n=44） and 1.0％ （n=2）,respectively.The incidence of grade 3 and 4 adverse events included severe diarrhea （13.4％,27/202） and severe neutropenia （9.4％,19/202）.There was no significant difference in the incidence of between grade 3 or 4 and grade 1 or 2 diarrhea and neutropenia in the UGT1A1 TA6/TA6 and TA6/TA7 genotypes （both P＞0.05）.Severe diarrhea was reported in two cases （100％） and severe neutropenia in a single case （50％） in patients with TA7/TA7 genotypes.Conclusion The detection of UGT1A1 gene polymorphisms prior to chemotherapy with Irinotecan helps screen the high-risk population and forecast the serious adverse events,thus steering rational use of medications.