發(fā)布時(shí)間：2019-05-12 17:53

【摘要】：目的XPA結(jié)合蛋白2(XAB2)可與轉(zhuǎn)錄偶聯(lián)特異性修復(fù)蛋白CSA、CSB和RNA聚合酶II等相互作用共同完成機(jī)體對(duì)內(nèi)外環(huán)境引起DNA損傷的核苷酸切除修復(fù)過程。XAB2在腫瘤發(fā)生發(fā)展過程中發(fā)揮重要作用。本研究旨在探討XAB2標(biāo)簽遺傳變異與非小細(xì)胞肺癌發(fā)病風(fēng)險(xiǎn)的關(guān)系,為探索非小細(xì)胞肺癌發(fā)病機(jī)制及篩選易感人群提供理論依據(jù)。方法采用以醫(yī)院為基礎(chǔ)的病例對(duì)照研究方法,分析XAB2標(biāo)簽遺傳變異與非小細(xì)胞肺癌發(fā)病風(fēng)險(xiǎn)的關(guān)系。研究對(duì)象為2008年1月至2012年12月在唐山市工人醫(yī)院就診的470例肺癌患者和470例同時(shí)期健康體檢者。根據(jù)Hapmap數(shù)據(jù)庫提供的數(shù)據(jù),采用Haploview 4.2軟件分析了中國人群XAB2基因上的標(biāo)簽SNPs(tag SNPs)。使用i Plex Gold Genotyping Assay和Sequenom Mass Array基因分型技術(shù)對(duì)目標(biāo)遺傳變異進(jìn)行基因分型。使用χ2檢驗(yàn)比較病例組與對(duì)照組之間年齡、性別以及吸煙狀況的差異;使用非條件Logistic回歸方法計(jì)算調(diào)整性別、年齡、吸煙情況后的OR值(odds ratio,ORs)和95%置信區(qū)間(confidence interval,95%CI)分析XAB2基因多態(tài)與非小細(xì)胞肺癌易感性的關(guān)系。結(jié)果本研究分析了位于XAB2基因的5個(gè)tag SNPs(rs4134816,rs4134819,rs4134860,rs794078,rs794083),發(fā)現(xiàn)XAB2基因rs794078和rs4134816多態(tài)與非小細(xì)胞肺癌的發(fā)病風(fēng)險(xiǎn)相關(guān)。非條件Logistic回歸分析顯示,攜帶XAB2rs794078 AA基因型較GG基因型攜帶者非小細(xì)胞肺癌發(fā)病風(fēng)險(xiǎn)顯著降低(OR=0.12;95%CI=0.03~0.54);和rs4134816 TT基因型攜帶者相比,至少攜帶一個(gè)C等位基因的個(gè)體非小細(xì)胞肺癌的發(fā)病風(fēng)險(xiǎn)顯著降低(OR=0.46;95%CI=0.26~0.84)。本研究數(shù)據(jù)沒有顯示XAB2其他標(biāo)簽SNPs顯著影響非小細(xì)胞肺癌的發(fā)病風(fēng)險(xiǎn)。性別分層分析顯示,攜帶rs4134816 CC或CT基因型的個(gè)體在男性人群中顯著降低非小細(xì)胞肺癌的發(fā)病風(fēng)險(xiǎn),其OR值為0.39(95%CI=0.18~0.82,P=0.013),但在女性人群中則并不影響非小細(xì)胞肺癌發(fā)病風(fēng)險(xiǎn),其OR值為0.68(95%CI=0.29~1.59,P=0.37)。在年齡分層分析中,我們發(fā)現(xiàn)年齡小于等于60歲的人群中,至少攜帶一個(gè)C等位基因的個(gè)體非小細(xì)胞肺癌的發(fā)病風(fēng)險(xiǎn)較低(OR=0.35;95%CI=0.17~0.74,P=0.006);但是在大于60歲的人群中并未發(fā)現(xiàn)這一差異(OR=0.98;95%CI=0.40~2.39,P=0.97)。吸煙分層分析結(jié)果顯示,至少攜帶一個(gè)C等位基因者較TT基因型攜帶者非小細(xì)胞肺癌的發(fā)病風(fēng)險(xiǎn)在吸煙組和非吸煙組中均無改變,其OR值和95%CI分別為0.51(0.26~1.03)和0.47(0.19~1.20),差異均無統(tǒng)計(jì)學(xué)意義(P0.05)。未發(fā)現(xiàn)XAB2基因其他標(biāo)簽SNPs與性別、年齡和吸煙狀況影響非小細(xì)胞肺癌發(fā)病風(fēng)險(xiǎn)。結(jié)論XAB2標(biāo)簽SNP(rs794078和rs4134816)影響非小細(xì)胞肺癌發(fā)病風(fēng)險(xiǎn)。進(jìn)一步證實(shí)XAB2在非小細(xì)胞肺癌中起到至關(guān)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 鹵0.82, P 鈮，

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