遗传多态性对接受紫杉烷与铂类联合治疗上皮性卵巢癌患者临床结果的影响

Effects of Genetic Polymorphisms on Clinical Outcomes of Patients with Epithelial Ovarian Cancer Treated with Taxanes and Platinum

通过测定接受紫杉烷与铂类联合治疗的上皮性卵巢癌患者的药物反应、毒性和生存数,评估遗传多态性对上皮性卵巢癌(EOC)患者治疗临床结果的影响。对2006年3月至2010年11月的118例患者的临床资料进行分析,患者接受了剖腹诊断肿瘤分期手术,并使用紫杉烷与铂类联合辅助化疗。使用单碱基引物测定法研究了ERCC1 N118N、ERCC18092C>A、ERCC2 K751Q、XRCC1 R399Q、XRCC1 R194W、ABCB13435C>T、ABCB12677G>T/A、GSTP1 I105V、GSTM1和GSTT1的多态性。多元Logistic回归分析法表明:GSTT1多态性的非空白基因型是对预后不良因素的总响应(校正后OR,0.29;95%CI,0.17~0.67),GSTP1 I105V多态性的A/A基因型及ABCB12677G>T/A多态性的T/T、T/A或A/A基因型是3级或4级血液学毒性(校正后OR,3.08;95%CI,1.12~8.43)和消化道毒性(校正后OR,9.74;95%CI,1.59~15.85)的重要影响因素。此外,多元Cox比例风险回归分析表明,ERCC18092C>A多态性的C/A或A/A基因型与GSTT1多态性的非空白基因型是低无进展生存期(校正后HR,1.94;95%CI,1.07~3.51)和低生存数(校正后HR,1.65;95%CI,1.79~3.42)的预后因子。ERCC18092C>A、ABCB12677G>T/A、GSTP1 I105V和GSTT1的遗传多态性对接受紫杉烷与铂类联合治疗的上皮性卵巢癌患者的药物反应、毒性和生存数有影响。但是,仍需要大规模的前瞻性临床研究来深入评估遗传多态性的影响。

To assess the effect of genetic polymorphism on the clinical outcome of epithelial ovarian cancer(EOC)patients,the drug response,toxicity and survival of epithelial ovarian cancer patients treated with paclitaxane and platinum were measured.The clinical data of 118 patients from March 2006 to November 2010 were analyzed.The patients underwent laparotomy for staging of tumors and used taxanes and platinum for adjuvant chemotherapy.Single nucleotide primer assays were used to investigate the polymorphisms of ERCC1 N118 N,ERCC18092 C>A,ERCC2 K751 Q,XRCC1 R399 Q,XRCC1 R194W,ABCB13435 C>T,ABCB12677 G>T/A,GSTP11105 V,GSTM1 and GSTT1.Multivariate logistic regression analysis showed that the nonwhite genotype of the GSTT1 polymorphism was the overall response to poor prognostic factors(adjusted OR,0.29;95%CI,0.17-0.67).A/A genotype of GSTP1 I105 V polymorphism and T/T,T/A,or A/A genotypes of ABCB12677 G>T/A polymorphism were important influencing factors of grade 3 or grade 4 hematologic toxicity(adjusted OR,3.08;95%CI,1.12~8.43)and digestive tract toxicity(adjusted OR,9.74;95%CI,1.59~15.85).In addition,multivariate Cox proportional hazards regression analysis showed that the C/A or A/A genotype of the ERCC18092 C>A polymorphism and the non-white genotype of the GSTT1 polymorphism were low progressionfree survival(adjusted HR,1.94;95%CI,1.07-3.51)and low survival(adjusted HR,1.65;95%CI,1.79-3.42)prognostic factors.Genetic polymorphisms of ERCC18092 C>A,ABCB12677 G>T/A,GSTP1 I105 V and GSTT1 affect the drug response,toxicity and survival of patients with epithelial ovarian cancer treated with taxane and platinum.However,large-scale prospective clinical studies are still needed to thoroughly assess the impact of genetic polymorphisms.