转录偶联修复基因XAB2遗传变异与肺癌发病风险关系研究

发布时间：2019-05-12 17:53

【摘要】：目的XPA结合蛋白2(XAB2)可与转录偶联特异性修复蛋白CSA、CSB和RNA聚合酶II等相互作用共同完成机体对内外环境引起DNA损伤的核苷酸切除修复过程。XAB2在肿瘤发生发展过程中发挥重要作用。本研究旨在探讨XAB2标签遗传变异与非小细胞肺癌发病风险的关系,为探索非小细胞肺癌发病机制及筛选易感人群提供理论依据。方法采用以医院为基础的病例对照研究方法,分析XAB2标签遗传变异与非小细胞肺癌发病风险的关系。研究对象为2008年1月至2012年12月在唐山市工人医院就诊的470例肺癌患者和470例同时期健康体检者。根据Hapmap数据库提供的数据,采用Haploview 4.2软件分析了中国人群XAB2基因上的标签SNPs(tag SNPs)。使用i Plex Gold Genotyping Assay和Sequenom Mass Array基因分型技术对目标遗传变异进行基因分型。使用χ2检验比较病例组与对照组之间年龄、性别以及吸烟状况的差异;使用非条件Logistic回归方法计算调整性别、年龄、吸烟情况后的OR值(odds ratio,ORs)和95%置信区间(confidence interval,95%CI)分析XAB2基因多态与非小细胞肺癌易感性的关系。结果本研究分析了位于XAB2基因的5个tag SNPs(rs4134816,rs4134819,rs4134860,rs794078,rs794083),发现XAB2基因rs794078和rs4134816多态与非小细胞肺癌的发病风险相关。非条件Logistic回归分析显示,携带XAB2rs794078 AA基因型较GG基因型携带者非小细胞肺癌发病风险显著降低(OR=0.12;95%CI=0.03~0.54);和rs4134816 TT基因型携带者相比,至少携带一个C等位基因的个体非小细胞肺癌的发病风险显著降低(OR=0.46;95%CI=0.26~0.84)。本研究数据没有显示XAB2其他标签SNPs显著影响非小细胞肺癌的发病风险。性别分层分析显示,携带rs4134816 CC或CT基因型的个体在男性人群中显著降低非小细胞肺癌的发病风险,其OR值为0.39(95%CI=0.18~0.82,P=0.013),但在女性人群中则并不影响非小细胞肺癌发病风险,其OR值为0.68(95%CI=0.29~1.59,P=0.37)。在年龄分层分析中,我们发现年龄小于等于60岁的人群中,至少携带一个C等位基因的个体非小细胞肺癌的发病风险较低(OR=0.35;95%CI=0.17~0.74,P=0.006);但是在大于60岁的人群中并未发现这一差异(OR=0.98;95%CI=0.40~2.39,P=0.97)。吸烟分层分析结果显示,至少携带一个C等位基因者较TT基因型携带者非小细胞肺癌的发病风险在吸烟组和非吸烟组中均无改变,其OR值和95%CI分别为0.51(0.26~1.03)和0.47(0.19~1.20),差异均无统计学意义(P0.05)。未发现XAB2基因其他标签SNPs与性别、年龄和吸烟状况影响非小细胞肺癌发病风险。结论XAB2标签SNP(rs794078和rs4134816)影响非小细胞肺癌发病风险。进一步证实XAB2在非小细胞肺癌中起到至关重要的作用。
[Abstract]:Objective XPA binding protein 2 (XAB2) can be coupled with transcriptional specific repair protein CSA,. The interaction of CSB and RNA polymerase II completes the process of nucleotidyl resection and repair of DNA damage caused by internal and external environment. XAB2 plays an important role in tumorigenesis and development. The purpose of this study was to investigate the relationship between genetic variation of XAB2 tags and the risk of non-small cell lung cancer (NSCLC), and to provide theoretical basis for exploring the pathogenesis of NSCLC and screening susceptible population. Methods A hospital-based case-control study was used to analyze the relationship between genetic variation of XAB2 tags and the risk of non-small cell lung cancer (NSCLC). From January 2008 to December 2012, 470 patients with lung cancer and 470 patients with health examination in Tangshan Workers Hospital were enrolled in the study. According to the data provided by Hapmap database, the label SNPs (tag SNPs). On XAB2 gene in Chinese population was analyzed by Haploview 4.2 software. I Plex Gold Genotyping Assay and Sequenom Mass Array genotyping techniques were used to genotype the target genetic variation. The differences of age, sex and smoking status between the case group and the control group were compared by 蠂 2 test. Non-conditional Logistic regression method was used to calculate OR value (odds ratio,ORs) and 95% confidence interval (confidence interval,95%CI) after sex, age, smoking and 95% confidence interval (confidence interval,95%CI) to analyze the relationship between XAB2 gene polymorphism and susceptibility to non-small cell lung cancer (NSCLC). Results five tag SNPs (rs4134816,rs4134819,rs4134860,rs794078,rs794083 located in XAB2 gene were analyzed. It was found that rs794078 and rs4134816 polymorphism of XAB2 gene were associated with the risk of non-small cell lung cancer (NSCLC). Non-conditional Logistic regression analysis showed that the risk of non-small cell lung cancer (OR=0.12;95%CI=0.03~0.54) in carriers with XAB2rs794078 AA genotype was significantly lower than that in carriers with GG genotype (OR=0.12;95%CI=0.03~0.54). Compared with rs4134816 TT genotypic carriers, individuals carrying at least one C allele had a significantly lower risk of non-small cell lung cancer (OR=0.46;95%CI=0.26~0.84). The data of this study did not show that other XAB2 tags SNPs significantly affected the risk of non-small cell lung cancer. Sex stratification analysis showed that individuals with rs4134816 CC or CT genotype significantly reduced the risk of non-small cell lung cancer in male population, with OR value of 0.39 (95% CI 0.18 卤0.82, P 鈮，

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