CYP1B1基因多态性与紫杉醇不良反应的相关性研究(1)
[摘要] 目的 探讨肿瘤患者CYP1B1基因多态性与紫杉醇不良反应的关系。 方法 选择我院2016年1月～2018年5月接受紫杉醇化疗的肿瘤患者52例作为研究对象，检测其CYP1B1基因型，并观察、收集、记录其不良反应发生情况，分析患者的不良反应发生和基因多态性的相关性。 结果 本研究共检测了27个基因位点，仅11个基因位点发生突变，其余16个基因位点均为野生型。其中，在CYP1B1*2/*5/*6/*7(142 C>G)和CYP1B1*2/*6/*7(355 G>T)基因多态性中，野生型基因患者的白细胞减少不良反应发生率高于突变型基因，差异有统计学意义(P<0.05);其余不良反应发生率比较，差异无统计学意义(P>0.05)。 结论 CYP1B1基因多态性与紫杉醇的不良反应具有一定的相关性。
[关键词] 紫杉醇;基因多态性;CYP1B1;不良反应
[中图分类号] R969 [文献标识码] A [文章编号] 1673-9701(2019)15-0039-04
Study on the correlation between CYP1B1 gene polymorphism and adverse reactions of paclitaxel
XU Qiuxia1 YE Lei2 ZHOU Xiping3 CHEN Wenfa1 CHEN Jincheng1 GAO Yali1
1.Department of Pharmacy， the Second Affiliated Hospital of Fujian Medical University， Quanzhou 362000， China; 2.Department of TCM， the Second Affiliated Hospital of Fujian Medical University， Quanzhou 362000， China; 3.Department of Pharmacy， Hospital of Quanzhou Taiwanese Investment Zone， Quanzhou 362700， China
[Abstract] Objective To investigate the correlation between CYP1B1 gene polymorphism and adverse reactions of paclitaxel. Methods A total of 52 patients with tumor who were given chemotherapy with paclitaxel from January 2016 to May 2018 were selected as the study subjects. The CYP1B1 gene type was detected， and adverse reactions were observed， collected and recorded. The correlation between gene polymorphism and adverse reactions was analyzed. Results A total of 27 gene sites were detected in the study. Only 11 gene sites were mutated， and the other 16 gene sites were wild type. Among the gene polymorphism of CYP1B1*2/*5/*6/*7 (142 C>G) and CYP1B1*2/*6/*7(355 G>T)， the incidence rate of adverse reaction of leukopenia in the patients with wild type gene was higher than that in the patients with mutated gene， and the difference was statistically significant(P<0.05); the differences in the incidence rates of other adverse reactions were not statistically significant(P>0.05). Conclusion There is a certain correlation between CYP1B1 gene polymorphism and adverse reactions of paclitaxel.
[Key words] Paclitaxel; Gene polymorphism; CYP1B1; Adverse reactions
隨着个体化治疗学理念的不断完善，个体药物基因多态性与不良反应相关性的研究越来越受重视，许多成果被应用于临床上，以指导临床合理规范用药。细胞色素酶P450 1B1(cytochrome P450 1B1，CYP1B1)为细胞色素酶P450超家族成员之一，是一种血红素-硫醇盐单加氧酶，主要催化17-β-雌二醇(E2)的羟化作用，参与多种恶性肿瘤的发病过程[1]。CYP1B1基因多态性的改变可能影响癌症的易感和预后，有研究发现CYP1B1基因多态性与紫杉醇的代谢有一定的关系[2]。在临床中，紫杉醇是治疗癌症的基本药物，与其他抗肿瘤药物相似，具有治疗窗窄、毒副作用大的特点。紫杉醇引起的不良反应主要表现为过敏反应、骨髓抑制、神经毒性、消化系统反应、肌肉或关节疼痛反应、心脏毒性、脱发、皮肤毒性反应、液体潴留和血管性水肿等[3]，由于紫杉醇不良反应个体差异的存在，在一定程度上限制了其应用[4]。有文献认为，紫杉醇发生的不良反应与药物代谢酶与转运酶的基因多态性相关[5]。因此，为了减少紫杉醇不良反应的发生，提高其疗效，开展紫杉醇药物基因组学及其应用是有必要的。本文主要研究肿瘤患者CYP1B1基因多态性对紫杉醇不良反应的影响，为临床合理使用紫杉醇提供依据。, 百拇医药(许秋霞 叶磊 周细萍 陈文发 陈金成 高雅莉)
[关键词] 紫杉醇;基因多态性;CYP1B1;不良反应
[中图分类号] R969 [文献标识码] A [文章编号] 1673-9701(2019)15-0039-04
Study on the correlation between CYP1B1 gene polymorphism and adverse reactions of paclitaxel
XU Qiuxia1 YE Lei2 ZHOU Xiping3 CHEN Wenfa1 CHEN Jincheng1 GAO Yali1
1.Department of Pharmacy， the Second Affiliated Hospital of Fujian Medical University， Quanzhou 362000， China; 2.Department of TCM， the Second Affiliated Hospital of Fujian Medical University， Quanzhou 362000， China; 3.Department of Pharmacy， Hospital of Quanzhou Taiwanese Investment Zone， Quanzhou 362700， China
[Abstract] Objective To investigate the correlation between CYP1B1 gene polymorphism and adverse reactions of paclitaxel. Methods A total of 52 patients with tumor who were given chemotherapy with paclitaxel from January 2016 to May 2018 were selected as the study subjects. The CYP1B1 gene type was detected， and adverse reactions were observed， collected and recorded. The correlation between gene polymorphism and adverse reactions was analyzed. Results A total of 27 gene sites were detected in the study. Only 11 gene sites were mutated， and the other 16 gene sites were wild type. Among the gene polymorphism of CYP1B1*2/*5/*6/*7 (142 C>G) and CYP1B1*2/*6/*7(355 G>T)， the incidence rate of adverse reaction of leukopenia in the patients with wild type gene was higher than that in the patients with mutated gene， and the difference was statistically significant(P<0.05); the differences in the incidence rates of other adverse reactions were not statistically significant(P>0.05). Conclusion There is a certain correlation between CYP1B1 gene polymorphism and adverse reactions of paclitaxel.
[Key words] Paclitaxel; Gene polymorphism; CYP1B1; Adverse reactions
隨着个体化治疗学理念的不断完善，个体药物基因多态性与不良反应相关性的研究越来越受重视，许多成果被应用于临床上，以指导临床合理规范用药。细胞色素酶P450 1B1(cytochrome P450 1B1，CYP1B1)为细胞色素酶P450超家族成员之一，是一种血红素-硫醇盐单加氧酶，主要催化17-β-雌二醇(E2)的羟化作用，参与多种恶性肿瘤的发病过程[1]。CYP1B1基因多态性的改变可能影响癌症的易感和预后，有研究发现CYP1B1基因多态性与紫杉醇的代谢有一定的关系[2]。在临床中，紫杉醇是治疗癌症的基本药物，与其他抗肿瘤药物相似，具有治疗窗窄、毒副作用大的特点。紫杉醇引起的不良反应主要表现为过敏反应、骨髓抑制、神经毒性、消化系统反应、肌肉或关节疼痛反应、心脏毒性、脱发、皮肤毒性反应、液体潴留和血管性水肿等[3]，由于紫杉醇不良反应个体差异的存在，在一定程度上限制了其应用[4]。有文献认为，紫杉醇发生的不良反应与药物代谢酶与转运酶的基因多态性相关[5]。因此，为了减少紫杉醇不良反应的发生，提高其疗效，开展紫杉醇药物基因组学及其应用是有必要的。本文主要研究肿瘤患者CYP1B1基因多态性对紫杉醇不良反应的影响，为临床合理使用紫杉醇提供依据。, 百拇医药(许秋霞 叶磊 周细萍 陈文发 陈金成 高雅莉)