本文選題：腦膠質(zhì)瘤　切入點：病例-對照研究　出處：《西北大學》2015年碩士論文　論文類型：學位論文

【摘要】：背景：膠質(zhì)瘤是最具侵略性的腫瘤之一。目前的證據(jù)表明,大部分的遺傳風險對膠質(zhì)瘤易感性起主要作用,而且膠質(zhì)瘤是由多個低風險的突變共同遺傳的。這些突變已經(jīng)被確定,通過相關的研究,諸如全基因組關聯(lián)研究。這就逐步引導腦膠質(zhì)瘤流行病學研究人員專注于找尋相關膠質(zhì)瘤的潛在致病因素。方法：我們采用病例-對照的研究策略,選取2010年12月至2014年4月期間來自唐都醫(yī)院423例膠質(zhì)瘤患者和302例健康對照,對54個基因上的78個單核苷酸多態(tài)性位點進行了腦膠質(zhì)瘤與遺傳因素的關聯(lián)分析研究。我們使用Sequenom MassARRAY RS1000基因分型技術進行SNP分析。我們利用exact test方法對對照組進行Hardy-Weinberg平衡檢驗；無條件Logistics回歸方法計算風險等位基因的相對優(yōu)勢比odds ratios和95%的置信區(qū)間,衡量這些突變等位基因與膠質(zhì)瘤的相關效應。利用Haploview和SNPstats分析位于同一個基因上若干個位點的連鎖程度及單體型效應。結果：在等位基因模型下,TERTrs2853676, FGFRrs730437,rs11506105和rs1468727, GSTPlrs1695, SHANK2rs7124728與腦膠質(zhì)瘤患病風險強烈相關(p0.05);IL4rs2243248, TERTrs2853676, EGFRrs730437, rs11506105 和 rs1468727, CCDC26 rs6470745, SHANKK2rs7124728, PLCB2rs 12439272與星形膠質(zhì)瘤患病風險強烈相關(p0.05)；RPA3rs4140805位點與膠質(zhì)母細胞瘤患病風險強烈相關。邏輯回歸分析發(fā)現(xiàn),在Log-additive模型下,EGFRrs730437、rs11506105、rs845552增加膠質(zhì)瘤的患病風險。在隱性模型下,EGFRrs1468727CC基因型增加膠質(zhì)瘤的發(fā)病風險。在Log-additive遺傳模式下,EGFRrs730437、rs11506105增加星型細胞瘤的患病風險。在隱性模型下,EGFRrs1468727CC基因型增加星型細胞瘤的患病風險。隱性模型下,TP53rs1042522CC基因型提高了腦膠質(zhì)瘤的患病風險。顯性模型下,GSTPlrs1695AG-GG基因型個體與攜帶AA者比較,其患膠質(zhì)瘤的風險降低了30%。在隱性模型下,CCDC26rs6470745GG降低了星型細胞瘤的發(fā)生風險；在顯性模型下,CCDC26 rs891835增加了膠質(zhì)母細胞瘤患病風險。IL4Rrs1801275的突變等位基因降低了膠質(zhì)瘤和膠質(zhì)母細胞瘤的風險；TERT rs2853676增加了腦膠質(zhì)瘤和星型細胞瘤的發(fā)生風險。在顯性模型下,RPA3rs2160138和rs4140805增加膠質(zhì)母細胞瘤的發(fā)病風險；在Log-additive模型下,YRCC5rs9288516位點的突變降低了膠質(zhì)母細胞瘤的發(fā)病風險。邏輯回歸分析顯示EGFR單體型CGT增加腦膠質(zhì)瘤和星形細胞瘤的發(fā)生風險。結論：我們的研究結果結合先前的研究表明, EGFR, TERT, CCDC26, RPA3, XRCC5, GSTP1, IL4R, TP53這些基因可能跟腦膠質(zhì)瘤或星型細胞瘤或膠質(zhì)母細胞瘤的發(fā)病風險有關,但結果仍需進一步驗證。
[Abstract]:Background: glioma is one of the most aggressive tumors. Current evidence suggests that most genetic risks play a major role in glioma susceptibility. And gliomas are inherited by multiple, low-risk mutations. These mutations have been identified, and have been studied. For example, genome-wide association studies. This gradually leads glioma epidemiologists to focus on identifying potential risk factors for glioma. Methods: we use a case-control study strategy. From December 2010 to April 2014, 423 glioma patients from Tangdu Hospital and 302 healthy controls were selected. 78 single nucleotide polymorphisms (SNP) loci of 54 genes were analyzed by correlation analysis between glioma and genetic factors. We used Sequenom MassARRAY RS1000 genotyping technique for SNP analysis. Exact test method was used to test Hardy-Weinberg balance in control group. The relative advantage of risk alleles calculated by unconditional Logistics regression method was higher than that of odds ratios and 95% confidence intervals. Haploview and SNPstats were used to analyze the linkage degree and haplotype effect of several loci in the same gene. Results: in allelic model, Haploview rs730437rs11506105 and rs1468727, GST plrs1695, SHANK2rs7124728 and GST plrs1695 were used to analyze the relationship between these alleles and glioma. Results: in allelic model, the alleles were identified as tertrs2853676, FGFRrs730437rs11506105 and rs1468727. The risk of glioma was strongly associated with p0.05rs2243248, TERTrs2853676, EGFRrs730437, rs11506105 and rs1468727, CCDC26 rs6470745, SHANKK2rs7124728, PLCB2rs 12439272 and glioma risk. EGFRrs730437 rs1150610552 increased the risk of glioma. In recessive model, EGFRrs1468727CC increased the risk of glioma. EGFRRs730437rs11506105 increased the risk of astrocytoma in recessive model. TP53rs1042522CC genotype increased the risk of glioma. The individuals with GSTPlrs1695AG-GG genotype in dominant model were compared with those with AA. CCDC26rs6470745GG decreased the risk of astrocytoma. In dominant model, CCDC26 rs891835 increased the risk of glioblastoma. IL4Rrs1801275 allele decreased the risk of glioma and glioblastoma. TERT rs2853676 increased the risk of glioma and astrocytoma. RPA3rs2160138 and rs4140805 increased the risk of glioblastoma. The mutation of YRCC5rs9288516 in Log-additive model reduced the risk of glioblastoma. Logical regression analysis showed that EGFR haplotype CGT increased the risk of glioma and astrocytoma. Previous studies have shown that EGFR, TERT, CCDC26, RPA3, XRCC5, GSTP1, IL4R, TP53 may be associated with the risk of glioma or astrocytoma or glioblastoma. However, the results still need to be further verified.
【學位授予單位】：西北大學
【學位級別】：碩士
【學位授予年份】：2015
【分類號】：R739.4

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