中国汉族癌症患者紫杉醇相关外周感觉神经病变的单核苷酸基因多态性  

Single Nucleotide Polymorphisms of Paclitaxel-induced Peripheral Sensory Neuropathy in Chinese Han Population

作　　者：窦雪琳 麦毓麟[2] 孙昭 王颖轶 邵亚娟 程月娟 周娜 骆飞 张彪[3] 白春梅 马水清[4] 

机构地区：[1]中国医学科学院北京协和医学院北京协和医院肿瘤内科,北京100052 [2]中国医学科学院北京协和医学院北京协和医院内科,北京100730 [3]中国医学科学院基础医学研究所北京协和医学院基础学院流行病与卫生统计系,北京100005 [4]中国医学科学院北京协和医学院北京协和医院妇产科,北京100730

出　　处：《中国医学科学院学报》2017年第5期593-601,共9页Acta Academiae Medicinae Sinicae

基　　金：国家自然科学基金(81472785;61435001);北京协和医学院研究生创新基金~~

摘　　要：目的在中国汉族人群中研究与2/3级紫杉醇介导的外周感觉神经病变(PSN)相关的单核苷酸基因多态性(SNP)位点及临床特点。方法以2014年5月至2016年12月在北京协和医院接受紫杉醇方案化疗的216例患者为研究对象,提取外周血DNA,选取8个候选SNP位点,采用Sequenom Mass ARRARYi PLEX平台测定基因型。依据美国国家癌症研究院-不良反应常见术语评定标准,由受训的临床医生完成患者随访及PSN分级。结果共有209例患者最终纳入分析。在候选SNP位点中,仅rs4141404∶A>C(LIMK2)与2/3级PSN显著相关(OR:4.32,95%CI:2.37~7.89,P<0.0001)。多因素Logistic回归分析结果显示,rs4141404∶A>C(LIMK2)多态性及既往使用铂类制剂(OR:2.70,95%CI:1.32~5.51,P=0.007)与2/3级PSN发生风险相关。结论 rs4141404∶A>C(LIMK2)多态性可能是中国汉族人群发生紫杉醇介导的2/3级PSN的风险因素。Objective To study the single nucleotide polymorphisms( SNPs) that predict a patient'srisk of grade 2-3 paclitaxel-induced peripheral sensory neuropathy( PSN) in Chinese Han populations. Methods Totally 216 patients received paclitaxel in Peking Union Medical College Hospital from May 2014 to December2016 were enrolled. DNA was isolated from peripheral blood. Genotyping for eight candidate SNPs was performed on Sequenom-Mass ARRARYi PLEX platform. Patients were followed up and PSN was assessed by trained physicians according to National Cancer Institute-Common Terminology Criteria for Adverse Events v4. 03. Results A total of 209 patients entered the final analysis. Among the candidate SNPs,only rs4141404∶ A > C( LIMK2) was significantly associated with grade 2/3 PSN( OR: 4. 32,95% CI: 2. 37-7. 89,P < 0. 0001). In multivariate logistic regression analysis,both rs4141404∶ A > C( LIMK2) and history of receiving platinum compound( OR:2. 70,95% CI: 1. 32-5. 51,P = 0. 007) were associated with grade 2/3 PSN. Conclusion rs4141404 ∶ A > C( LIMK2) may be the markers of risk of grade 2/3 PSN.

关 键 词：紫杉醇 外周感觉神经病变 化疗不良反应 中国汉族人群 

分 类 号：R730.53[医药卫生—肿瘤]