胃肠间质瘤患者BIRC5基因多态性与伊马替尼疗效及骨髓抑制的相关性研究  

Association of polymorphisms in BIRC5 with the efficacy and myelosuppression of Imatinib in gastrointestinal stromal tumor patients.

作　　者：周晓君 邱海波[2] 庄玮[1] 张晓旭 周志伟[2] 黄民[1] 王雪丁[1] ZHOU Xiao-jun;QIU Hai-bo;ZHUANG Wei;ZHANG Xiao-xu;ZHOU Zhi-wei;HUANG Min;WANG Xue-ding(Institute of Clinical Pharmacology,School of Pharmaceutical Sciences,Sun Yat-sen University,Guangzhou510006,Guangdong Province,China;Department of Gastric Surgery Cancer Center,Sun Yat-sen University,Guangzhou 510060,Guangdong Province,China)

机构地区：[1]中山大学药学院临床药理研究所,广东广州510006 [2]中山大学肿瘤防治中心胃外科,广东广州510060

出　　处：《中国临床药理学杂志》2019年第23期2988-2991,共4页The Chinese Journal of Clinical Pharmacology

基　　金：国家自然科学基金资助项目(81473283,81173131)

摘　　要：目的探讨BIRC5常见单核苷酸多态性(rs2239680/rs11868371/rs1042542/rs9904341/rs1042489/rs4789551)与胃肠间质瘤(GIST)患者伊马替尼(IM)疗效及骨髓抑制的相关性。方法收集180例接受IM治疗的GIST患者的外周血,记录疗效[其中79例有完整无进展生存期(PFS)]及药物不良反应等临床信息;通过Sequenom iPLEXTM Mass Assay平台检测BIRC5基因多态性。结果rs2239680 TC+CC患者的PFS为61.00个月显著优于TT的51.54个月,差异有统计学意义(P<0.05)。rs11868371 GG+CC携带者比GC携带者更容易发生重度骨髓抑制(26.09%vs 2.86%,P<0.01);rs1042489 TT携带者比CT+CC携带者更容易发生重度骨髓抑制(33.93%vs 16.22%,P<0.01)。其他单核苷酸多态性未发现与疗效及骨髓抑制有关。结论BIRC5 rs2239680与IM的疗效有关,BIRC5 rs11868371和rs1042489与骨髓抑制的严重程度有关。Objective To investigate association of single nucleotide polymorphisms in BIRC5(rs2239680/rs11868371/rs1042542/rs9904341/rs1042489/rs4789551)with the efficacy and myelosuppression of Imatinib(IM)in gastrointestinal stromal tumor(GIST)patients.Methods Peripheral blood samples were obtained from GIST patients who received IM therapy(n=180),and clinical information including efficacy[79 cases with complete progression free survival(PFS)]and adverse reactions were recorded;Polymorphisms of BIRC5 were detected by Sequenom iPLEXTM Mass Assay platform.Results The PFS of rs2239680 TC+CC carriers was 61.00 months,which was significant better than 51.54 months of TT carriers,and the difference was statistically significant(P<0.05).rs11868371 GG+CC carriers were more prone to severe mye-losuppression than GC carriers(26.09%vs 2.86%,P<0.01);rs1042489 TT carriers were more susceptible to severe myelosuppression than CT+CC carriers(33.93%vs 16.22%,P<0.01).No other single nucleotide polymorphisms were found to be associated with efficacy or myelosuppression(P>0.05).Conclusion In GIST,the polymorphism of BIRC5 rs2239680 was related to the efficacy of Imatinib,while the polymorphisms of BIRC5 rs11868371 and rs1042489 were both related to the severity of Imatinib-induced myelosuppression.

关 键 词：伊马替尼 基因多态性 胃肠间质瘤 BIRC5 

分 类 号：R979.1[医药卫生—药品]