中国西安汉族人群脑胶质瘤及其亚型遗传易感性关联研究

发布时间：2018-03-19 02:12

本文选题：脑胶质瘤　切入点：病例-对照研究　出处：《西北大学》2015年硕士论文　论文类型：学位论文

【摘要】：背景：胶质瘤是最具侵略性的肿瘤之一。目前的证据表明,大部分的遗传风险对胶质瘤易感性起主要作用,而且胶质瘤是由多个低风险的突变共同遗传的。这些突变已经被确定,通过相关的研究,诸如全基因组关联研究。这就逐步引导脑胶质瘤流行病学研究人员专注于找寻相关胶质瘤的潜在致病因素。方法：我们采用病例-对照的研究策略,选取2010年12月至2014年4月期间来自唐都医院423例胶质瘤患者和302例健康对照,对54个基因上的78个单核苷酸多态性位点进行了脑胶质瘤与遗传因素的关联分析研究。我们使用Sequenom MassARRAY RS1000基因分型技术进行SNP分析。我们利用exact test方法对对照组进行Hardy-Weinberg平衡检验；无条件Logistics回归方法计算风险等位基因的相对优势比odds ratios和95%的置信区间,衡量这些突变等位基因与胶质瘤的相关效应。利用Haploview和SNPstats分析位于同一个基因上若干个位点的连锁程度及单体型效应。结果：在等位基因模型下,TERTrs2853676, FGFRrs730437,rs11506105和rs1468727, GSTPlrs1695, SHANK2rs7124728与脑胶质瘤患病风险强烈相关(p0.05);IL4rs2243248, TERTrs2853676, EGFRrs730437, rs11506105 和 rs1468727, CCDC26 rs6470745, SHANKK2rs7124728, PLCB2rs 12439272与星形胶质瘤患病风险强烈相关(p0.05)；RPA3rs4140805位点与胶质母细胞瘤患病风险强烈相关。逻辑回归分析发现,在Log-additive模型下,EGFRrs730437、rs11506105、rs845552增加胶质瘤的患病风险。在隐性模型下,EGFRrs1468727CC基因型增加胶质瘤的发病风险。在Log-additive遗传模式下,EGFRrs730437、rs11506105增加星型细胞瘤的患病风险。在隐性模型下,EGFRrs1468727CC基因型增加星型细胞瘤的患病风险。隐性模型下,TP53rs1042522CC基因型提高了脑胶质瘤的患病风险。显性模型下,GSTPlrs1695AG-GG基因型个体与携带AA者比较,其患胶质瘤的风险降低了30%。在隐性模型下,CCDC26rs6470745GG降低了星型细胞瘤的发生风险；在显性模型下,CCDC26 rs891835增加了胶质母细胞瘤患病风险。IL4Rrs1801275的突变等位基因降低了胶质瘤和胶质母细胞瘤的风险；TERT rs2853676增加了脑胶质瘤和星型细胞瘤的发生风险。在显性模型下,RPA3rs2160138和rs4140805增加胶质母细胞瘤的发病风险；在Log-additive模型下,YRCC5rs9288516位点的突变降低了胶质母细胞瘤的发病风险。逻辑回归分析显示EGFR单体型CGT增加脑胶质瘤和星形细胞瘤的发生风险。结论：我们的研究结果结合先前的研究表明, EGFR, TERT, CCDC26, RPA3, XRCC5, GSTP1, IL4R, TP53这些基因可能跟脑胶质瘤或星型细胞瘤或胶质母细胞瘤的发病风险有关,但结果仍需进一步验证。
[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.
【学位授予单位】：西北大学
【学位级别】：硕士
【学位授予年份】：2015
【分类号】：R739.4

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