UGT1A1*6基因多态性与IP方案治疗广泛期小细胞肺癌患者临床疗效和毒副反应的相关性分析  

Correlative Analysis of UGT1A1*6 Polymorphism with Toxity and Efficacy of IP Chemotherapy in the Treatment of ED-SCLC

作　　者：何奕[1] 赵瑾[1] 龚倩[1] 罗以[1] 袁志军[1] 杨烁[1] 

机构地区：[1]中南大学湘雅医学院附属肿瘤医院老干内科,湖南长沙410013

出　　处：《肿瘤药学》2014年第3期182-186,共5页Anti-Tumor Pharmacy

摘　　要：目的：探讨尿苷二磷酸葡萄糖醛酸转移酶1A1＊6（UGT1A1＊6）基因多态性与IP方案治疗的广泛期小细胞肺癌（ED-SCLC）患者临床疗效和毒副反应的相关性。方法选择2010年3月至2013年4月我院应用IP方案治疗的46例ED-SCLC患者，化疗前采全血提取基因组DNA，PCR法扩增目的基因片段，焦磷酸测序法测定UGT1A1＊6的基因多态性，化疗过程中观察并分析患者的临床疗效及不良反应的发生情况，探讨UGT1A1＊6基因多态性与不良反应和疗效之间的关系。结果46例患者中，UGT1A1＊6位点野生型G/G 34例（73％），杂合突变型G/A 8例（17％），纯合突变型A/A 4例（8％）。化疗期间，突变杂合型（G/A）及纯合突变型（A/A）患者3-4级腹泻和中性粒细胞减少的发生率明显高于UGT1A1野生型（G/G）（P〈0.05），UGT1A1＊6各种基因型之间血小板减少的发生率比较，差异无统计学意义（P〉0.05）。结论 UGT1A1＊6基因多态性与IP方案治疗ED-SCLC发生严重的腹泻和中性粒细胞减少有关，但与其临床疗效无关。Objective To investigate the correlation of UGT1A1＊6 gene polymorphisms and clinical efficacy and toxic-ity of patients with extensive disease small-cell lung cancer （ED-SCLC） treated by IP regimen. Methods 46 patients with ED-SCLC treated by IP regimen from March 2010 to April 2013 were selected. Before chemotherapy, the UGT1A1＊6 ge-netic polymorphism was analyzed by pyrosequencing method after blood genomic DNA extraction and PCR assay to amplify the target gene fragment. During the chemotherapy, the clinical efficacies and adverse reactions were observed and recorded to investigate the correlation of UGT1A1 gene polymorphisms with side effects and clinical efficacy. Results In 46 patients, there were 34 cases of UGT1A1＊6 wild-type G/G which accounted for 73%, 8 cases of heterozygous mutant-type G/A which accounted for 17%, and 4 cases of homozygous mutant-type A/A which accounted for 8%. During the chemotherapy, the incidence rates of Grade 3-4 diarrhea and neutropenia of patients with UGT1A1＊6 G/A and UGT1A1＊6 A/A mutant-type genotype were significantly higher than on those with UGT1A1＊6 A/A wild-type genotype （P〈0.05）, while no significant differences of curative effect were observed for different genotypes （P〉0.05）. Conclusion UGT1A1＊6 gene polymorphism was correlated with the incidence of severe diarrhea and neutropenia among the ED-SCLC patients treated by IP regimen, but had no correlation with the clinical efficacy of IP regimen.

关 键 词：尿苷二磷酸葡萄糖醛酸转移酶1A1＊6 基因多态性 伊立替康 广泛期小细胞肺癌 

分 类 号：R734.2[医药卫生—肿瘤]