WISP1基因多态性与肺癌易感性及铂类药物化疗敏感性的关系  

Association of WISP1 Polymorphisms with Lung Cancer Susceptibility and Platinum-based Chemotherapy Sensitivity

作　　者：陈娟[1] 尹继业[1] 王瑛[1] 李湘平[1] 郑艺[1] 钱晨月[1] 刘昭前[1] 

机构地区：[1]中南大学临床药理研究所遗传药理学湖南省重点实验室,湖南长沙410078

出　　处：《肿瘤药学》2013年第6期479-479,共1页Anti-Tumor Pharmacy

摘　　要：wnt诱导信号通路蛋白1（wntinduciblesignalingpathwayprotein1，WISPl）是生长因子CCN家族的成员。前期研究发现WISPl基因多态性与多种肺疾病的发生发展相关，包括哮喘、急性肺损伤等。本研究旨在探索WISPl基因多态性是否与肺癌易感性及肺癌铂类药物化疗敏感性相关。我们在中南大学湘雅医院收集了325例肺癌患者及254例健康对照血样。根据实体瘤化疗敏感性评价指南（RECIST）筛选出118例化疗敏感和174例化疗耐药的患者。所有血液样本均用Promega公司生产的基因组DNA纯化试剂盒提取基因组DNA。我们根据以下原则挑选了47个候选单核苷酸多态性位点（singlenucleotidePolymorphism，SNP）：（1）在中国人群中最小等位基因频率（MinorAlleleFrequency，MAF）不小于5％；（2）2基因区域的标签SNP；（3）位于启动子、3’非翻译区（UTR）和外显子区的SNPs。基因区域的标签SNPs（r^2≥0．8）运用Haploview4．2软件来挑选，所有SNPs都通过飞行质谱（sequenom）方法进行分型。所有SNP位点都进行Hardy—Weinberg平衡检验，并通过非条件Logistic回归计算OR值来评价多态与肺癌易感性及化疗敏感性的关系。OR值的计算校正了以下因素：年龄、性别、吸烟状况、肿瘤病理类型、肿瘤分级和化疗方案，并且运用Bonferroni校正法进行多重检验校正。所有统计分析采用SPSS130和PLINK1．07软件完成。经统计学分析，我们发现rs2977549与非小细胞肺癌患者化疗敏感性显著相关（P≤0．001），并且与小细胞肺癌患者化疗敏感性（P=0．017）及肺癌易感性（P=0．026）也具有相关性，但后两者经校正后差异无统计学意义。因此，我们认为WISPrs2977549有可能是非小细胞肺癌铂类药物化疗敏感性的一个诊断标志物。Wnt inducible signaling pathway protein 1 （＇WISP1） belongs to the CCN family of growth factors. It was reported that its polymorphisms correlated to several lung diseases including asthma and ventilator-induced lung injury. In this study, we aimed to test the hypothesis that WISP1 polymorphisms may be a^ssociated with lung cancer susceptibiliW and platinum-based chemotherapy response in Chinese population. DNA samples of 325 lung cancer patients and 254 health controls were collected from Xiangya Hospital of Central South University. Revised RECIST Guideline was used to define the chemotherapy response, we identified 118 chemotherapy sensitivity and 174 chemotherapy resist- ant patients. The genomic DNA of all recruited subjects was extracted using Promega Wizard Genomic DNA Purification kit. 47 SNPs were selected by the following criteria： （1） minor allele frequency （MAF） was larger than 5 % in Chinese population; （2） they were haplotype tag- ger SNPs along WISP1 gene region; （3） if they were not tagger SNPs, they were SNPs located in promoter region, 3＇ UT1K, or exon region, either missence mutation or nonsense mutation. Haplotype tagger SNPs were selected using pair-wised tagging with default setting （pair- wise r2 threshold 0.80）. It was performed by Haploview 4.2. All SNPs were genotyped by Sequenom MassARICAY. For statistical analysis, the observed genotype frequencies in patients and controls compared with expected frequencies under Hardy - Weinberg equilibrium were evaluated by the X 2 test. Unconditional logistic regression was used to estimate the association of lung cancer risk and chemotherapeutic re- sponse by calculating odds ratios （OR）. The O1K of drug response was adjusted according to age, sex, smoking status, tumour histology, stage and therapeutic reginaens. Bonferroni Correction was used to correct multiple comparisons. All statistical analysis was perfomled using either SPSS 13.0 or PLINK 1.07 software. We found that rs2977549 was significantly associated wi

关 键 词：化疗敏感性 肺癌易感性 基因多态性 铂类药物 条件LOGISTIC 单核苷酸多态性位点 非小细胞肺癌 中南大学湘雅医院 

分 类 号：R734.2[医药卫生—肿瘤]