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.

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.