CYP1B1*3药物基因检测在紫杉醇个体化用药中的应用研究

Application of CYP1B1*3 pharmacogene detection in individualized drug use of paclitaxel

目的探究肿瘤患者CYP1B1*3基因多态性与紫杉醇不良反应的相关性,同时检验该基因指导安全用药的效果,为紫杉醇在临床精准使用提供科学依据。方法本研究共分为两个部分:①选取我院2019年8月~2021年12月接受紫杉醇化疗的肿瘤患者104例作为研究对象,采用荧光原位杂交技术(FISH)检测CYP1B1*3(1294 C>G)基因型,观察、收集、记录其药物不良反应(ADR)发生情况,通过药品关联性评价找出紫杉醇导致的ADR,分析ADR和CYP1B1*3基因多态性的相关性;②选取我院2022年1~4月接受紫杉醇化疗的60例肿瘤患者为研究对象,随机分为个体化给药组和常规治疗组,各30例,个体化给药组行CYP1B1*3(1294 C>G)基因检测并根据基因结果及患者个体情况调整给药剂量,常规治疗组无基因筛查,直接按照标准剂量给药,比较两组不良反应发生情况。结果基因相关性研究中,CYP1B1*3野生型基因的肿瘤患者骨髓抑制、胃肠道反应发生率明显高于突变型基因患者,差异有统计学意义(P<0.05);个体化给药研究中,个体化给药组紫杉醇不良反应发生率明显低于常规治疗组,差异有统计学意义(P<0.05)。结论CYP1B1*3基因多态性与紫杉醇不良反应具有关联性,CYP1B1*3基因检测可提升肿瘤患者紫杉醇的用药安全性。

Objective To explore the correlation between CYP1B1*3 gene polymorphism and adverse reactions of Paclitaxel in tumor patients,and to test the effect of this gene in guiding safe medication,so as to provide scientific basis for the precise use of paclitaxel in clinic.Methods This study was divided into two parts:①Selected 104 tumor patients who received paclitaxel chemotherapy in our hospital from Aug 2019 to Dec 2021 as the research objects,and used fluorescence in situ hybridization(FISH)to detect the CYP1B1*3(1294 C>G)genotype.Observed,collected and recorded the occurrence of adverse drug reactions(ADR),finded out the ADR caused by paclitaxel through drug association evaluation,and analyzed the correlation between ADR and CYP1B1*3 gene polymorphisms;②Selected 60 tumor patients who received paclitaxel chemotherapy from Jan to Apr 2022 were randomly divided into individualized medication group(30 cases)and routine treatment group(30 cases).The individualized medication group underewent CYP1B1*3(1294 C>G)gene testing and adjusted the dosage besed on the genetic results and individual patient conditions.The routine treatment group without genetic screening was administered according to the standard dosage,and the incidence of adverse reactions were compared between the two groups.Results In the gene correlation study,the incidence of myelosuppression,gastrointestinal reactions in patients with CYP1B1*3 wild-type gene were significantly higher than those with mutant gene,and the differences were statistically significant(P<0.05).In the individualized medication study,the incidence of adverse reactions of paclitaxel in the individualized medication group was significantly lower than that in the routine treatment group,and the difference was statistically significant(P<0.05).Conclusion The CYP1B1*3 gene polymorphism is associated with the adverse reactions of paclitaxel.The detection of CYP1B1*3 gene can improve the safety of paclitaxel in tumor patients.