摘要
目的探讨尿苷二磷酸葡糖醛酸转移酶1A1(UGT1A1)基因多态性与伊立替康治疗小细胞肺癌(SCLC)疗效及预后的关系。方法根据化疗方法不同将60例SCLC患者分为观察组和对照组,各30例。观察组患者采用伊立替康联合顺铂治疗,对照组患者采用依托泊苷联合奈达铂治疗,比较两组患者的临床疗效、不良反应发生率和生存情况。检测观察组患者的UGT1A1基因多态性,统计其多态性分布。结果两组患者的客观缓解率(ORR)、不良反应发生率和无进展生存时间比较,差异均无统计学意义(P﹥0.05)。观察组中,UGT1A1*28基因型为基因启动子区TA序列呈6次重复的野生型(TA6/6)所占比例最高(76.67%),UGT1A1*6基因型为G/G野生型所占比例最高(60.00%)。观察组中,1例患者出现迟发性腹泻,其UGT1A1*28基因型为纯合突变型TA7/7,UGT1A1*6基因型为纯合突变型A/A;2例患者出现贫血,其UGT1A1*28基因型分别为杂合突变型TA6/7和纯合突变型TA7/7,UGT1A1*6基因型分别为杂合突变型G/A和纯合突变型A/A;2例患者出现消化道反应,其UGT1A1*28基因型均为纯合突变型TA7/7,UGT1A1*6基因型均为纯合突变型A/A;8例患者粒细胞减少,其UGT1A1*28基因型分别为4例野生型TA6/6、2例杂合突变型TA6/7、2例纯合突变型TA7/7,UGT1A1*6基因型分别为2例野生型G/G、4例杂合突变型G/A、2例纯合突变型A/A。结论临床使用伊立替康治疗SCLC时,配合UGT1A1基因多态性的检测,针对个体差异性设计适宜的治疗方案,合理指导临床用药,将有助于减少不良反应的发生。
Objective To investigate the relationship between the polymorphism of uridine diphosphoglucuronosyl transferase 1 A1(UGT1A1)gene and the efficacy of irinotecan in the treatment of small cell lung cancer(SCLC)as well as patients’prognosis.Method Sixty patients with SCLC receiving two different chemotherapy regimens were included as observation group or control group,with 30 cases in each.Patients in observation group were treated with irinotecan plus cisplatin,meanwhile those in control group were treated with etoposide plus nedaplatin.The clinical efficacy,incidence of adverse reactions and survival of the two groups were compared.The polymorphism of UGT1A1 gene was measured in observation group,besides the polymorphism distribution was statistically analyzed.Result The objective response rate(ORR),incidence of adverse reactions,and progression-free survival(PFS)were similar between the two groups(P>0.05).In observation group,the UGT1A1*28 genotype of wild type with 6 replicates of TA sequence of the gene promoter region(TA6/6)showed the highest proportion of 76.67%,and UGT1A1*6 genotype of G/G wild type was as high as 60.00%.In regard to the incidence of adverse reactions among patients in observation group,one patient had delayed diarrhea,the UGT1A1*28 genotype was homozygous mutation TA7/7,the UGT1A1*6 genotype was homozygous mutation A/A;two patients were anemia,the UGT1A1*28 genotypes were heterozygous mutation TA6/7 and homozygous mutation TA7/7,their UGT1A1*6 genotypes were heterozygous mutation G/A and homozygous mutation A/A respectively;two patients had digestive tract reaction,the UGT1A1*28 genotypes were both of homozygous mutation TA7/7 and the UGT1A1*6 genotypes were also both homozygous mutation A/A;eight patients developed granulocytopenia,among them,UGT1A1*28 genotypes of wild type TA6/6 were observed in 4 cases,heterozygous mutant TA6/7 were noted in 2 cases,while homozygous mutant TA7/7 were also observed in 2 cases,as to UGT1A1*6 genotypes,2 cases were with wild type G/G,4 cases were with heterozygous mutant G/A,and 2 cases were with homozygous mutant A/A.Conclusion During clinical practice,the clinical use of irinotecan,along with polymorphism detection of UGT1A1 gene,and appropriate design of regimen based on individual differences,would guide the clinical medication,thereby reducing adverse reactions.
作者
曹亮
姬泽萱
张长洪
刘建华
陈艳红
支学军
CAO Liang;JI Zexuan;ZHANG Changhong;LIU Jianhua;CHEN Yanhong;ZHI Xuejun(Department of Respiratory Medicine,the First Affiliated Hospital of Hebei North University,Zhangjiakou 075000,Hebei,China)
出处
《癌症进展》
2019年第20期2441-2444,共4页
Oncology Progress
基金
张家口市2018年度市级科技计划自筹经费项目(1821150H)
