摘要
目的探讨伊立替康化疗不良反应与尿苷二磷酸葡糖醛酸转移酶(UGT)1A1基因TATA盒区域基因多态性的关系。方法 32例恶性肿瘤患者在使用伊立替康治疗前采集外周血1 m L,提取外周血的基因组DNA,测定UGT1A1基因启动子区TATA盒区域中TA序列重复出现的频率;观察患者使用伊立替康治疗后的不良反应,并统计分析TA6/TA6、TA6/TA7、TA7/TA7基因型出现的频率及其与伊立替康相关不良反应之间的关系。结果 32例患者中共检测到UGT1A1纯合子TA6/TA6 23例(71.88%),杂合突变型TA6/TA7 9例(28.12%),未发现纯合子TA7/TA7型患者。TA6/TA6和TA6/TA7基因型患者出现Ⅲ度以上延迟性腹泻、血小板减少、白细胞减少及呕吐等不良反应的发生率均明显低于0-Ⅱ度患者(均P<0.05);TA6/TA7Ⅲ-Ⅳ度患者延迟性腹泻、白细胞减少、血小板减少及呕吐的发生率均高于纯合子TA6/TA6的Ⅲ-Ⅳ度患者(均P<0.05)。结论在应用伊立替康进行化疗前行UGTIA1基因多态性的检测可以筛查高危人群,预测伊立替康的严重不良反应,以便指导临床用药。
Objective To investigate the relationship between irinotecan-associated adverse effects and uridine diphosphate glucuronosyl transferase 1A1 （UGT1A1） gene polymorphism.Methods Perip-heral blood samples （1 mL） were taken from 32 patients with malignant tumors before irinotecan treatment.Genome DNA was extracted from peripheral blood to examine the frequency of UGT1A1 TATA box thymine-adenine （TA） repeats.Irinotecan-related adverse events were observed. In addition, the relationship between frequencies of TA6/TA6, TA6/TA7 and TA7/TA7 and irinotecan-associated adverse effects was analyzed.Results Among the 32 patients, 23 had （71.88%） TA6/TA6 genotype and 9 had TA6/TA7 genotype （28.12%）. No TA7/TA7 genotype was found in all patients.Grade 3 and above adverse reactions,including delayed diarrhea,thombocytopenia,leucopenia and vomiting,occurred obviously less often than grade 0 to 2 adverse reactions in patients with either genotype TA6/TA6 or genotype TA6/TA7 （P〈0.05）.Graed 3 and 4 adverse reactions （delayed diarrhea,leucopenia,thrombocy-topenia and vomiting） occurred more often in patients with genotype TA6/TA7 than patients with genotype TA6/TA6 （P〈0.05）.Conclusion The detection of UGT1A1 gene polymorphism prior to chemotherapy with irinotecan can screen the high risk population, predict the irinotecan-related adverse events and serve as a guide to clinical medication.
出处
《实用临床医学（江西）》
CAS
2014年第11期1-3,共3页
Practical Clinical Medicine
