摘要
目的:探讨ABCB1基因多态性与紫杉醇类药物致乳腺癌患者骨髓抑制的相关性。方法:回顾性分析2019年10月至2022年12月该院收治的160例乳腺癌患者的病例资料。患者采用以紫杉醇类药物为基础的治疗方案。采用单因素和Logistic回归分析ABCB1基因型等影响因素与患者应用紫杉醇类药物发生骨髓抑制的相关性。采用基因型分层分析其相关性。采用SHEsis在线软件分析ABCB1基因型的连锁不平衡效应。结果:体重指数、ABCB1 G2677T基因型和分子亚型对骨髓抑制有影响(P<0.05)。与应用注射用紫杉醇(白蛋白结合型)的患者相比,应用注射用紫杉醇脂质体的患者致中重度骨髓抑制(P=0.03)、中重度白细胞减少(P=0.01)和中重度中性粒细胞减少(P<0.05)的发生率较低;ABCB12677TT基因型患者应用多西他赛注射液致骨髓抑制的发生率高于GT和GG基因型者(P<0.05),差异均有统计学意义。ABCB1基因位点之间存在连锁不平衡,但ABCB1单倍型与患者发生骨髓抑制不良反应之间的差异无统计学意义(P>0.05)。结论:对于乳腺癌患者,临床上评估紫杉醇类药物不良反应时,除考虑体重指数、分子亚型和紫杉醇类药物的类型外,还需要综合考虑患者的基因型及基因-基因交互作用。
OBJECTIVE:To explore the correlation of ABCB1 gene polymorphism and myelosuppression with taxanes application in breast cancer patients.METHODS:From Oct.2019 to Dec.2022,a total of 160 patients diagnosed with breast cancer in Affiliated Taian Central Hospital of Qingdao University were retrospectively analyzed.All patients were treated with a taxanes drug-based regimen.Univariate and Logistic regression were used to analyze the correlation with myelosuppression such as ABCB1 genotype.The correlation was analyzed by using gene stratification.Linkage disequilibrium effect of ABCB1 genotype was analyzed by SHEsis online software.RESULTS:Body mass index,ABCB1 G2677T genotype and molecular subtype had an effect on myelosuppression with significant difference(P<0.05).Compared with patients receiving taxanes for injection(albumin-bound),the incidences of moderate-to-severe myelosuppression(P=0.03),moderate-to-severe leukopenia(P=0.01)and moderate-to-severe neutrophilia(P<0.05)were lower in liposomes of taxanes for injection;the incidence of myelosuppression in patients with ABCB12677TT genotype was higher than those with GT and GG genotypes(P<0.05),with statistically significant differences.There was linkage disequilibrium in ABCB1 loci,yet the difference between ABCB1 haplotypes and the occurrence of myelosuppressive in patients was not statistically significant(P>0.05).CONCLUSIONS:In patients with breast cancer,clinical assessment of adverse drug reactions of taxanes requires a comprehensive consideration of the patients’genotype and gene-gene interactions,in addition to body mass index,molecular subtype,and type of taxanes.
作者
张恕芳
耿晓宁
邰晓鹏
张林
刘伦
刘富垒
ZHANG Shufang;GENG Xiaoning;TAI Xiaopeng;ZHANG Lin;LIU Lun;LIU Fulei(Dept.of Pharmacy,Affiliated Taian Central Hospital of Qingdao University,Shandong Taian 271000,China;Dept.of Breast Diseases,Affiliated Taian Central Hospital of Qingdao University,Shandong Taian 271000,China;Dept.of Scientific Research,Affiliated Taian Central Hospital of Qingdao University,Shandong Taian 271000,China)
出处
《中国医院用药评价与分析》
2024年第7期827-832,共6页
Evaluation and Analysis of Drug-use in Hospitals of China
基金
山东省药品不良反应监测中心委托项目(No.药化-2022SDADRKY11)
山东省医学会治疗药物监测科研基金项目(No.YXH2020ZX060)
泰安市科技创新发展计划项目(No.2021NS340)。
关键词
乳腺癌
紫杉醇
多西他赛
不良反应
基因型
Breast cancer
Taxanes
Docetaxel
Adverse drug reactions
Genotype
