“CYP2D6”基因多态性和NSCLC靶向治疗后肝损伤、皮疹及腹泻的相关性

Association between CYP2D6 gene polymorphism and liver injury,rash,and diarrhea after targetedtherapy inpatients with non⁃small cell lung cancer

目的比较非小细胞肺癌(non⁃small cell lung cancer,NSCLC)患者CYP2D6×10与CYP2D6×5基因多态性的差异与经靶向治疗(吉非替尼、厄洛替尼、克唑替尼)后出现肝损伤,皮疹,腹泻不良反应的相关性,探索靶向药物治疗常见不良反应与CYP2D6基因多态性的关联。方法选择新疆医科大学附属肿瘤医院2016年1月至2019年12月经靶向治疗(吉非替尼、厄洛替尼、克唑替尼)的NSCLC患者,采用限制性片段长度多态性聚合酶链反应(polymerase chain reaction⁃restriction fragment length polymorphism,PCR⁃RFLP)检测患者CYP2D6×10与CYP2D6×5基因型分布及等位基因频率。比较基因型分布差异和等位基因差异在出现肝损伤、腹泻、皮疹组与无患者组的差异。结果CYP2D6×10基因多态性及等位基因频率在发生肝损害组与无肝损害组差异有统计学意义(P<0.05),皮疹组和腹泻组均与CYP2D6×10基因多态性及等位基因频率差异无相关性。腹泻有关的唯一相关因素是否有化疗史(P=0.002),皮疹相关的因素是分期P=0.000。结论NSCLC靶向治疗药物性肝损伤的预测方面CYP2D6基因多态性可能是其中有效的指标之一,可指导NSCLC患者临床用药。

Objective To compare the differences between CYP2D6×10 and CYP2D6×5 gene polymorphisms in patients with non⁃small cell lung cancer(NSCLC)and the correlation between liver injury,skin rash and diarrhea adverse reactions after targeted therapy(geffitinib,erlotinib and crizotinib),and to explore the correlation between common adverse reactions after targeted drug therapy and CYP2D6 gene polymorphism.Methods NSCLC patients treated with targeted therapy(gifitinib,Erlotinib,crezoltini)from January 2016 to December 2019 were selected from the Affiliated Tumor Hospital of Xinjiang Medical University.The polymorphism of CYP2D6×10 and CYP2D6×5 genotypes and allelic frequencies were detected by using the restricted segment length polymorphism polymerase Chain reaction⁃restriction fragment Length polymorphism(PCR⁃RFLP).Genotype distribution differences and allelic differences in patients with liver injury,diarrhea,and rash were compared with those without.Results There were statistically significant differences in CYP2D6×10 gene polymorphism and allele frequency between the groups with and without liver damage(P<0.05),and there was no correlation between CYP2D6×10 gene polymorphism and allele frequency difference between the skin rash group and the diarrhea group.The only factor associated with diarrhea was a history of chemotherapy(P=0.002),and the factor associated with rash was staging(P=0.000).Conclusion CYP2D6 gene polymorphism may be one of the effective indicators for the prediction of drug⁃induced liver injury in TARGETED NSCLC therapy,which can guide the clinical medication of NSCLC patients.