脑胶质瘤发病风险相关遗传多态性的发掘和鉴定研究

发布时间：2018-04-22 08:32

本文选题：脑胶质瘤 + RAD52　；参考：《北京化工大学》2014年硕士论文

【摘要】：在中枢神经系统的癌症中脑胶质瘤占大约80%,预后较差。我们运用病例-对照研究方法,针对404例脑胶质瘤病人和经过筛选的性别年龄均匹配的820例正常对照,系统研究了RAD52基因和白细胞端粒长度相关遗传变异与脑胶质瘤遗传易感性的相关关系。针对DNA修复基因RAD52,我们对其基因座位中的5个单核苷酸多态性(single nucleotide polymorphism, SNP) (rs 1051669,rs10774474,rs1 1571378,rs7963551和rs6489769)进行了基因分型。进而,采用logistic回归分析计算比值比(Odds Ratios,OR值)和95%置信区间(Confidence Interval, CI),揭示了上述SNP与脑胶质瘤发病风险的关联。我们发现,只有RAD52rs7963551 SNP与脑胶质瘤的易感性显著相关。与携带有AA基因型的个体相比,携带rs7963551 AC或CC基因型个体的OR值分别为0.49(95%CI=0.37-0.65,P=9.29×10-6)或0.39(95%CI=0.18-0.81,P=0.012)。分层分析显示,rs7963551 SNP与星形细胞瘤(P=6.3×10-6)或少突星形细胞肿瘤(P=0.002)的发表风险显著相关。前人发现外周血白细胞端粒长度(leukocyte telomere length,LTL)较短与欧洲人群中的某些癌症发病风险呈现明显相关性。同时在欧洲人群中发现,14q21 rs398652以及1p34.2 rs621559两个SNP与LTL显著相关。我们的前期研究显示,在中国人群中LTL相关的两个SNP位点(14q2l rs398652和1p34.2 rs621559)和食管鳞状细胞癌的发病风险相关。基于此,本研究系统揭示了中国北方人群中rs621559和rs398652 SNP与脑胶质瘤遗传易感性的关系。我们以404例脑胶质瘤以及820例正常对照样本为研究对象,对14q2l rs398652和1p34.2 rs621559两个SNP进行基因分型。我们发现,具有1p34.2rs621559 AG或GG基因大]型的受试者其OR值为1.82(95%CI=1.07-3.09,P=0.026)或2.12(95%CI=1.26-3.56,P=0.005),与具有rs621559 AA基因型的受试者相比更易罹患脑胶质瘤。类似地,与14q21 rs398652 AA基因型相比,AG或GG基因型(OR=1.39,957石CI=1.07-1.80,P=0.012;OR=1.52,95%CI=1.04-2.20,P=0.029)显著增加脑胶质瘤患病风险。我们的研究结果首次鉴定了中国人群中脑胶质瘤发病风险相关的RAD52 rs7963551多态性以及LTL相关的两个遗传多态rs621559和rs398652。
[Abstract]:Gliomas account for about 80 percent of cancer in the central nervous system, with poor prognosis. We used a case-control study to study 404 glioma patients and 820 normal controls who were matched by sex and age. The relationship between genetic variation of RAD52 gene and leukocyte telomere length and genetic susceptibility to glioma was systematically studied. For the DNA repair gene RAD52, we genotyped five single nucleotide polymorphisms (SNPs) rs1051669, rs10774474, rs1 1571378, rs7963551 and rs64897669 in its locus. Furthermore, logistic regression analysis was used to calculate odds ratio odds ratio (OR) and 95% confidence interval (95% confidence interval), which revealed the association between the above SNP and the risk of glioma. We found that only RAD52rs7963551 SNP was significantly associated with glioma susceptibility. Compared with individuals with AA genotype, the OR values of individuals with rs7963551 AC or CC genotype were 0.4995, 0.37-0.65P9.29 脳 10 ~ (-6) or 0.3995% ~ 0.18-0.81C ~ (0.012), respectively. Stratified analysis showed that rs7963551 SNP was significantly associated with the published risk of astrocytoma (6. 3 脳 10-6) or oligodendroid astrocytoma (P0. 002). It was found that the shorter leukocyte telomere length in peripheral blood leukocytes was associated with the risk of some cancers in European population. At the same time, there was a significant correlation between SNP 14q21 rs398652 and 1p34.2 rs621559 and LTL in European population. Our previous study showed that two SNP loci associated with LTL were associated with the risk of esophageal squamous cell carcinoma in Chinese population (14q2l rs398652 and 1p34.2 rs621559). Based on these results, this study revealed the relationship between rs621559 and rs398652 SNP and genetic susceptibility to glioma in northern China. 14q2l rs398652 and 1p34.2 rs621559 were genotyped from 404 gliomas and 820 normal controls. We found that the OR of the subjects with 1p34.2rs621559 AG or GG gene] genotype was 1.82 ~ 95) or 2.12 ~ 95% ~ 1.26 ~ 3.09% P0. 026) or 2.12 ~ 95% CI = 1.26 ~ 56 ~ (6) P ~ (0.005), which was more likely to develop glioma than those with rs621559 AA genotype. Similarly, compared with the 14q21 rs398652 AA genotype, the AG or GG genotype OR1.39957 increased the risk of glioma significantly. Our results were the first to identify the RAD52 rs7963551 polymorphism associated with the risk of glioma in Chinese population, and two genetic polymorphisms associated with LTL, rs621559 and rs398652.
【学位授予单位】：北京化工大学
【学位级别】：硕士
【学位授予年份】：2014
【分类号】：R739.41

【参考文献】