Xu Q P, Xiao R D, Xiong W M, He F, Cai L
Department of Epidemiology and Health Statistics, School of Public Health, Fujian Medical University, Fuzhou 350108, China.
Zhonghua Yu Fang Yi Xue Za Zhi. 2018 Mar 6;52(3):243-252. doi: 10.3760/cma.j.issn.0253-9624.2018.03.006.
To analyze the relationship between single nucleotide polymorphisms (SNP) of Notch signaling pathway and susceptibility to lung cancer. 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 χ(2) and logistic regression model. The average age of cases and controls was (58.70±10.73) and (58.98±10.85) years old. The for genotype AC carriers of HEY1 rs1046472 was 0.80 (95% 0.66-0.97) when comparing with genotype CC. The for genotype AC+AA carriers of HEY1 rs1046472 was 0.81 (95% 0.67-0.98) when comparing with genotype CC. The for genotype AC carriers of HEY2 rs3734637 was 0.82 (95% 0.67-0.99) when comparing with genotype AA. In the stratified analysis, Notch3 rs3815188, DLL1 rs1033583, JAG1 rs8708, JAG2 rs9972231, HEY1 rs1046472, HEY2 rs3734637, HES2 rs11364 were associatied with the risk of lung cancer, 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 JAG1 rs8708 and family history, JAG2 rs9972231 and BMI had interaction in the study, were 2.07 (95% 1.21-3.52) and 1.73 (95% 1.21-2.47), respectively. Notch3 rs3815188, DLL1 rs1033583, JAG1 rs8708, JAG2 rs9972231, HEY1 rs1046472, HEY2 rs3734637 and HES2 rs11364 were significantly associated with susceptibility to lung cancer.
分析Notch信号通路单核苷酸多态性(SNP)与肺癌易感性之间的关系。本研究是以医院为基础的病例对照研究。选取2006年1月至2012年12月间福建和南京三家医院经组织病理学确诊的1121例肺癌患者作为病例组。同时,选取来自医院其他科室就诊患者或社区的1121名健康人群作为对照组,排除患有肿瘤、慢性病以及肺癌直系亲属的人群。采用统一问卷收集一般信息。运用基质辅助激光解吸电离飞行时间质谱(MALDI-TOF-MS)技术对1121例肺癌患者和1121名健康对照者的9个SNP(Notch3 rs3815188、Notch4 rs915894、Notch4 rs520692、DLL1 rs1033583、JAG1 rs8708、JAG2 rs9972231、HEY1 rs1046472、HEY2 rs3734637、HES2 rs11364)进行基因分型。通过χ²检验和logistic回归模型分析SNP与肺癌的关联。病例组和对照组的平均年龄分别为(58.70±10.73)岁和(58.98±10.85)岁。与CC基因型相比,HEY1 rs1046472基因型AC携带者的比值比为0.80(95%置信区间0.66 - 0.97)。与CC基因型相比,HEY1 rs1046472基因型AC + AA携带者的比值比为0.81(95%置信区间0.67 - 0.98)。与AA基因型相比,HEY2 rs3734637基因型AC携带者的比值比为0.82(95%置信区间0.67 - 0.99)。在分层分析中,Notch3 rs3815188、DLL1 rs1033583、JAG1 rs8708、JAG2 rs9972231、HEY1 rs1046472、HEY2 rs3734637、HES2 rs11364与肺癌风险相关,比值比分别为0.041、0.030、0.043、0.003、0.004、0.0