Notch信号通路相关基因多态性与肺癌易感性的关联研究  

Association between polymorphism in notch signaling pathway and lung cancer risk

作　　者：徐秋萍[1] 肖仁栋 熊为旻 何斐[1] 蔡琳[1] 

机构地区：[1]福建医科大学公共卫生学院流行病与卫生统计学系,福州350108 [2]福建医科大学公共卫生学院附属第一医院胸外科,福州350108

出　　处：《中华预防医学杂志》2018年第3期243-252,共10页Chinese Journal of Preventive Medicine

基　　金：国家自然科学基金（81402738）;福建省环保科技计划项目（2015R012）;福建省自然科学基金面上项目（2016J01355）

摘　　要：目的分析Notch信号通路相关基因单核苷酸多态性（SNP）与肺癌易感性的关系。方法采用以医院为基础的病例．对照设计，选择2006年1月至2012年12月收集在福建、南京三所医院中，经组织病理学诊断的新发原发性肺癌患者1121例；选取同期在医院其他科室的健康探视人群（排除肿瘤患者及其直系亲属和慢性病住院患者）和社区健康人群1121名，采用统一的调查表收集研究对象基本信息。应用基质辅助激光解析电离时间飞行质谱技术（MALDI-TOF．Ms）检测9个SNP位点（Notch3rs3815188、Notch4rs915894、Notch4rs520692、DLLlrsl033583、JAGlrs8708、JAG2rs9972231、HEYlrsl046472、HEY2rs3734637、I-IES2rsll364）的基因分型。采用X^2检验、非条件logistic回归模型分析各SNP位点多态性与肺癌的关联。结果病例组和对照组的年龄分别为（58．70±10．73）、（58．98＋10．85）岁。与HEYlrsl046472CC型基因型者相比，AC基因型携带者患肺癌OR=O．80，95％Ch0．66～0．97；与CC型相比，AC＋AA基因型携带者患肺癌风险OR=O．81，95％CI：0．67-0．98。与携带HEY2rs3734637AA相比，AC基因型发生肺癌的OR=O．82，95％CI：0．67-0．99。分层分析中，Notch3rs3815188、DLLlrsl033583、JAGlrs8708、JAG2rs997223l、liEYlrsl046472、HEY2rs3734637、HES2rsll364与肺癌发病风险存在关联（P值分别为0．041、0．030、0．043、0．003、0．004、0．026、0．038）。logistic回归模型相乘交互作用发现，JAGlrs8708与肿瘤家族史、JAG2rs9972231与BMI存在交互作用，OR值分别为2．07（95％CI：1．21～3．52）、1．73（95％CI：I．21～2．47）。结论Notch3rs3815188，DLLlrsl033583、JAGlrs8708、JAG2rs997223l、HEYlrsl0464727HEY2rs3734637友HES2rsl1364均与肺癌的易感性相关。Objective To analyze the relationship between single nucleotide polymorphisms （SNP） of Notch signaling pathway and susceptibility to lung cancer. Methods The present study was a hospital-based case-control study. All 1 121 patients of lung cancer diagnosed by histopathology three hospitals in Fujian and Nanjing were selected as cases from January 2006 to December 2012. At the same time, 1 121 healthy population from other departments of the hospital to visit patients or community, excluding those with tumor, chronic disease, and immediate family members of lung cancer, were enrolled in control group. A uniform questionnaire was used to collect general information. Matrix-assisted laster desorption ionization time of flight mass spectrometry （MALDI-TOF-MS） was used to identify the polymorphisms of 9 SNP （Notch3 rs3815188, Notch4 rs915894, Notch4 rs520692, DLL1 rs1033583, JAG1 rs8708, JAG2 rs9972231, HEY1 rs1046472, HEY2 rs3734637, HES2 rs11364） in 1 121 lung cancer patients and 1 121 healthy controls. The association between SNP and lung cancer was analyzed by X2 and logistic regression model. Results The average age of cases and controls was （58.70± 10.73） and （58.98±10.85） years old. The OR for genotype AC carriers of HEY1 rs1046472 was 0.80 （95%Ch 0.66-0.97） when comparing with genotype CC. The OR for genotype AC＋AA carriers of HEY 1 rs1046472 was 0.8 [ （95% Ch 0.67-0.98） when comparing with genotype CC. The OR for genotype AC carriers of HEY2 rs3734637 was 0.82 （95%C1： 0.67-0.99） when comparing with genotype AA. In the stratified analysis, Notch3 rs3815188, DLLI rsl033583, JAG1 rs8708, JAG2 rs9972231, HEY1 rs1046472, HEY2 rs3734637, HES2 rs11364 were associatied with the risk of lung cancer, P were 0.041, 0.030, 0.043, 0.003, 0.004, 0.026 and 0.038, respectively.The interactions analysis done by logistic regression model showed JAGI rs8708 and family history, JAG2 rs9972231 and BMI had interaction in the study, OR were 2.07 （95%Chl.21-3.52） and 1.73 （95%Chl.21-2.47�

关 键 词：多态性 单核苷酸 肺肿瘤 NOTCH信号通路 易感性 

分 类 号：R734.2[医药卫生—肿瘤]