RAD23B基因rs10759225位点多态性与含铂类方案治疗非小细胞肺癌疗效和血液学毒性的关系  

Association between RAD23B gene rs10759225 polymorphism and clinical outcomes of non-small cell lung cancer patients treated with platinum-based chemotherapy

作　　者：谢晓楠 文贻勇 凌琼颖 黄文锋[4] 覃芳卉[1] 王洪学[1] 周文献[1] 陆永奎[1] 谢裕安[1] 谢伟敏[1] XIE Xiaonan;WEN Yiyong;LING Qiongying;HUANG Wenfeng;QIN Fanghui;WANG Hongxue;ZHOU Wenxian;LU Yongkui;XIE Yuan;XIE Weimin(Department of Chemotherapy,the Affiliated Cancer Hospital of Guangxi Medical University,Nanning 530021,China;Guangxi Medical University Graduate School, Nanning 530021 , China;The First People Hospital of Changde City, Changde54100, China;Department of Oncology, the Second Affiliated Hospital of Guangxi Medical University, Nanning 530021 , China)

机构地区：[1]广西医科大学附属肿瘤医院化疗科,南宁530021 [2]广西医科大学研究生院,南宁530021 [3]常德市第一人民医院全科医学科,常德451000 [4]广西医科大学第二附属医院肿瘤内科,南宁530007

出　　处：《中国癌症防治杂志》2019年第2期151-157,共7页CHINESE JOURNAL OF ONCOLOGY PREVENTION AND TREATMENT

基　　金：国家自然科学基金项目(30960436);广西自然科学基金项目(桂科自0832234)

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。Objective To investigate the relationship between the rs10759225 polymorphism of the RAD23B 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(mPFS) 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/Ⅳ of 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 RAD23B 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.

关 键 词：非小细胞肺癌 化学治疗 铂类 RAD23B基因 单核苷酸多态性 基因型 

分 类 号：R734.2[医药卫生—肿瘤]