UGT1A1基因多态性与伊立替康治疗广泛期小细胞肺癌疗效和不良反应的关系  

Relationship between UGT1A1 Gene Polymorphism and Irinotecan Efficacy and Adverse Reactions of Irinotecan in the Treatment of Small Cell Lung Cancer at Extensive Stage

作　　者：肖晓光[1] 夏曙[1] 邹曼[1] 王淑静[1] 陈元[1] 

机构地区：[1]华中科技大学同济医学院附属同济医院肿瘤科,武汉430030

出　　处：《中国药师》2015年第10期1661-1666,共6页China Pharmacist

摘　　要：目的：探讨UGT1A1基因多态性在中国汉族广泛期小细胞肺癌患者人群中的分布情况,并探索UGT1A1基因多态性与CPT-11治疗广泛期小细胞肺癌的疗效和不良反应之间的关系。方法：外周血提取基因组DNA,采用PCR手段扩增目的基因片段,直接测序法分析2011年6月-2013年1月我院收治的67例广泛期小细胞肺癌患者UGT1A1＊28和UGT1A1＊6多态性分布,并对所有67例接受CPT-11为基础化疗方案的患者出现的不良反应;ORR,PFS和OS进行记录,并对不同基因型的患者进行比较。结果：67例患者中,UGT1A1＊28位点野生型TA6/6有56例（83.6%）,杂合突变型TA6/7有11例（16.4%）;UGT1A1＊6位点野生型G/G有45例（67.2%）,杂合突变型G/A有22例（32.8%）。各基因型间的ORR,PFS和OS比较无显著差异。UGT1A1＊6杂合突变型（G/A）可以增加患者发生3-4度以上腹泻（36.4%vs.6.6%,P〈0.05）和中性粒细胞下降（27.2%vs.4.4%,P〈0.05）的风险,UGT1A1＊28突变型（TA6/7）可以增加患者发生3-4度以上血小板下降（27.2%vs.1.8%,P〈0.05）的风险;将不同组合基因型之间的不良反应进行对比发现,同时出现TA6/7和G/A的双位点杂合变异的患者出现3-4级以上腹泻和中性粒细胞下降的风险显著增加（P〈0.05）。结论：UGT1A1基因多态性可以预测CPT-11对小细胞肺癌化疗的不良反应,但似无法预测其疗效。Objective：To analyze the distribution of UGT1A1 gene polymorphisms in Chinese Han patients with extensive-disease small cell lung cancer（ED-SCLC）,and evaluate the correlation between UGT1A1 gene polymorphisms and toxicity and efficacy of irino-tecan（CPT-11） based regimen in the patients with ED-SCLC. Methods： The analysis of UGT1A1＊28 and UGT1A1？6 gene poly-morphisms was performed in 67 patients with ED-SCLC admitted in our hospital from June 2011 to January 2013. The 67 cases with ED-SCLC treated with irinotecan（CPT-11） based regimen were enrolled to observe the adverse events and efficacy during the chemo-therapy, including objective responserate rate （ ORR） , progression free survival （ PFS） and overall survival （ OS） . The incidence of different genotypes was compared. Results：The distribution of UGT1A1 genotypes in the 67 patients was follows：UGT1A1？28 wild-type （WT） genotype TA6/6 （56, 83. 6%）, heterozygous genotype TA6/7 （11, 16. 4%）;UGT1A1＊6 wild-type （WT） genotype G/G （45,67. 2%）, heterozygous genotype G/A （22,32. 8%）. No significant difference of PFS and OS was observed between the differ-ent genotypes. The incidence of grade 3 and 4 delayed diarrhea and neutropenia in the patients carrying UGT1A1？6 G/A was higher than that in those with WT genotype （36. 4% vs. 6. 6%, P〈0. 05;27. 2% vs. 4. 4%, P〈0. 05, respectively）. The incidence of grade 3 and 4 thrombocytopenia in the patients carrying UGT1A1＊28 TA6/7 was higher than that in those with WT genotype （27. 2%vs. 1. 8%, P〈0. 05）. The patients simultaneously carrying UGT1A1＊28 TA6/7 and UGT1A1？6 G/A were prone to suffering 3 and 4 delayed diarrhea and neutropenia. Conclusion： UGT1A1 polymorphisms may predict the adverse events of CPT-11 in ED-SCLC, while can not predict the efficacy of CPT-11.

关 键 词：小细胞肺癌 伊立替康 预后 基因多态性 疗效 

分 类 号：R968[医药卫生—药理学]