【摘要】 目的探讨RAD23B基因rs10759225位点多态性与含铂类方案一线治疗中晚期非小细胞肺癌(non-small cell lung cancer,NSCLC)的疗效及血液学毒性的关系。方法回顾性收集接受含铂类联合方案一线治疗的150例NSCLC患者的临床资料及外周血样本,采用改良多重高温连接酶检测反应技术对rs10759225进行基因分型,并分析其与患者疗效及血液学毒性的关系。结果 150例NSCLC患者的总有效率(ORR)为28.7%(43/150)。与携带G/G基因型患者比较,携带A等位基因型(G/A和A/A)患者接受含铂类方案治疗的ORR显著提高(OR校正=1.780,95%CI:1.110～2.884,P=0.042)。全组患者中位无进展生存期(mPFS)为5.6个月,各基因型患者的mPFS差异均无统计学意义(P>0.05)。以G/G基因型为参照,A/A基因型与患者化疗后发生Ⅲ/Ⅳ度白细胞减少的风险相关(OR校正=0.468,95%CI:0.204～0.711,P=0.008);A等位基因型分别与患者发生Ⅲ/Ⅳ度中性粒细胞减少(OR校正=0.502,95%CI:0.155～0.887,P=0.022)和≥Ⅰ度血小板减少的风险有关(OR校正=0.494,95%CI:0.101～0.833,P=0.047);而G/A基因型与患者发生Ⅱ/Ⅲ度贫血的风险有关(OR校正=0.504,95%CI:0.213～0.890,P=0.047)。结论 RAD23B基因rs10759225位点多态性与含铂类方案治疗NSCLC的疗效及血液学毒性有关,但与患者的预后无关。与携带G/G基因型患者比较,携带A等位基因型患者的疗效更好,但发生骨髓抑制的风险更高。更多还原

【Abstract】 Objective To investigate the relationship between the rs10759225 polymorphism of the RAD23 B gene and clinical outcomes of platinum-based chemotherapy as first-line treatment in patients with advanced non-small cell lung cancer(NSCLC).Methods The clinical data and peripheral blood samples of 150 NSCLC patients receiving first-line treatment with platinum-based combination regimen were retrospectively analyzed. The polymorphism of rs10759225 was genotyped by improved multiple ligase detection reaction(iMLDR)technology. Results The overall response rate(ORR)was 27.8%(43/150)of all group.Compared with G/G genotype carriers,A allele(included G/A genotype and A/A genotype)carriers had markedly higher response rate(ORadjusted=1.780,95%CI:1.110-2.884,P=0.042).The median progression-free survival(m PFS)of all patients was 5.6 months,and there was no significance of mPFS among difference genotype groups(P>0.05). Compared with G/G genotype(as a reference),A/A genotype increased the risk of grade Ⅲ/Ⅳof leukopenia(ORadjusted=0.468,95%CI:0.204-0.711,P=0.008),and an allele was each associated with grade Ⅲ/Ⅳ of neutropenia(ORadjusted= 0.502,95 % CI :0.155-0.887,P = 0.022) and grade ≥Ⅰ of thrombocytopenia(ORadjusted= 0.494,95 % CI :0.101-0.833,P=0.047),respectively.The risk of grade Ⅱ/Ⅲ anemia was significantly higher in patients with G/A genotype compared with G/G genotype carriers(ORadjusted=0.504,95%CI:0.213～0.890,P=0.047). Conclusions RAD23 B gene rs10759225 polymorphism is associated with response rate and hematological toxicity of NSCLC patients treated with platinum-based chemotherapy,but there is no relationship between the polymorphism and the PFS of patients.Compared with G/G genotype carriers,A allele carriers may have better efficacy,and,as well as have a higher risk of myelosuppression.更多还原