CAJ | 학술논문

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.
목적:탐토UGT1A1기인다태성재중국한족엄범기소세포폐암환자인군중적분포정황,병탐색UGT1A1기인다태성여CPT-11치료엄범기소세포폐암적료효화불량반응지간적관계. 방법:외주혈제취기인조DNA,채용PCR수단확증목적기인편단,직접측서법분석2011년6월~2013년1월아원수치적67례엄범기소세포폐암환자UGT1A1?28 화UGT1A1?6다태성분포,병대소유67례접수CPT-11위기출화료방안적환자출현적불량반응;ORR,PFS화OS진행기록,병대불동기인형적환자진행비교. 결과: 67 례환자중,UGT1A1?28 위점야생형 TA6/6 유 56 례(83.6%),잡합돌변형 TA6/7 유 11 례(16. 4%);UGT1A1?6위점야생형G/G유45례(67. 2%),잡합돌변형G/A유22례(32. 8%). 각기인형간적ORR,PFS화OS비교무현저차이. UGT1A1?6잡합돌변형(G/A)가이증가환자발생3~4도이상복사(36. 4% vs. 6. 6% ,P<0. 05)화중성립세포하강(27. 2% vs. 4. 4%, P<0. 05)적풍험,UGT1A1?28돌변형(TA6/7)가이증가환자발생3~4 도이상혈소판하강(27. 2% vs. 1. 8%,P<0. 05)적풍험;장불동조합기인형지간적불량반응진행대비발현,동시출현TA6/7화G/A적쌍위점잡합변이적환자출현3~4급이상복사화중성립세포하강적풍험현저증가(P<0. 05). 결론: UGT1A1 기인다태성가이예측CPT-11대소세포폐암화료적불량반응,단사무법예측기료효.
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.