TOLL样受体基因多态性与胃癌及EBV相关胃癌易感性的研究

发布时间：2018-03-04 07:23

本文选题：胃癌　切入点：EBV　出处：《青岛大学》2016年硕士论文　论文类型：学位论文

【摘要】：目的:探讨TLR2(rs3804099、rs3804100),TLR4(rs11536889、rs10759932)和TLR9(TLR9-1486、TLR9-2848)基因多态性与胃癌和EBV相关胃癌(Epstein Barr virus-associated GC,EBVa GC)易感性的关系。方法:选用青岛地区EBV阴性的胃癌(EBVn GC)组织、EBVa GC组织及正常健康人群外周血标本作为研究对象,采用PCR结合RFLP的技术检测TLR2(rs3804099、rs3804100),TLR4(rs11536889、rs10759932)和TLR9(TLR9-1486、TLR9-2848)基因的多态性;对部分PCR产物进行测序,DNAStar软件对序列进行对比分析,验证PCR-RFLP基因分型结果;对实验结果进行统计处理,比较分析胃癌患者和健康对照组、EBVa GC组织和EBVn GC组织的基因型和等位基因频率。结果:(1)TLR2 rs3804099的基因型和等位基因频率在胃癌组与健康对照组间有显著性差异(χ2=5.617,p=0.018;χ2=6.467,p=0.011),胃癌组C等位的基因频率及C等位的基因携带者频率均显著高于正常健康对照组(χ2=6.467,p=0.011;χ2=4.444,p=0.035),并且与野生TT型相比,CC基因型可明显增加胃癌的发病率(OR=3.554,95%CI=1.179-10.715)。(2)TLR2rs3804100位点各基因型的频率、C等位基因及C等位基因携带者频率在胃癌组和正常健康对照组之间无明显差异(p0.05)。(3)TLR4(rs10759932)基因的多态性与青岛地区胃癌的发病率有明显相关性,携带TC和CC基因型可以减少胃癌的易感性(OR=0.483,95%CI=0.289-0.807),C等位基因可能是胃癌的保护基因,携带C等位基因可以显著降低胃癌的罹患风险。(4)TLR4(rs11536889)基因型、等位基因的频率、携带者的频率在胃癌组和健康对照组间均无显著差异(P0.05)。(5)胃癌组TLR9(1486T/C)和TLR9(C2848T)基因的多态性与对照组比较均无显著差异(P0.05)。(6)TLR2rs3804099、rs3804100;TLR4rs11536889、rs10759932;TLR9-1486、TLR9-2848基因多态性在EBVn GC与EBVa GC组间均无显著差异(P0.05)。结论:(1)TLR2 rs3804099基因的多态性可能与胃癌的发病率有关,C等位基因可能为胃癌的高危基因,携带C等位基因可能会增加胃癌的罹患率。(2)TLR4 rs10759932基因的多态性可能与胃癌的发病率有关,C等位基因可能为胃癌的保护基因,携带C等位基因可能会降低胃癌的罹患率。(3)TLR2(rs3804099、rs3804100);TLR4(rs11536889、rs10759932);TLR9-1486和TLR9-2848基因多态性与EBV的感染没有协同作用,与EBVa GC的易感性没有相关性。
[Abstract]:Objective: to investigate the relationship between the polymorphism of TLR2 rs3804099 rs3804100 (TLR4 rs11536889 rs10759932) and TLR9-1486 (TLR9-2848) gene polymorphism and the susceptibility to Epstein Barr virus-associated GCV-a GC of gastric cancer and EBV associated gastric cancer. PCR combined with RFLP was used to detect the polymorphism of TLR2 rs3804099 / rs3804100) and TLR9rs11536889 (rs10759932) and TLR9 / TLR9-1486 (TLR9-2848) respectively, and some PCR products were sequenced by DNAStar software to verify the results of PCR-RFLP genotyping. The genotypes and allelic frequencies of TLR2 rs3804099 in gastric cancer patients and healthy controls were compared and analyzed. Results there were significant differences in genotype and allele frequencies of TLR2 rs3804099 between gastric cancer patients and healthy controls (蠂 2 5.617 p0. 018, 蠂 2 6.467, p0.011, P 0. 011, P 0. 011, P 0. 011, P 0. 011, P 0. 011, P 0. 011, P 0. 011, P 0. 011). The frequency of C allele and C allele carrier in group C were significantly higher than those in normal control group (蠂 2 / 6.467), 蠂 ~ (2 +) = 4.444 / (P = 0.035), and compared with wild TT genotype, the frequency of CC genotype was significantly higher than that of wild TT genotype. The incidence of gastric cancer was significantly higher than that of control group (P < 0.05), and the frequency of genotype C of each genotype of TLR2rs3804100 was significantly higher than that of wild-type TT genotype (P < 0.05), which was higher than that of control group (蠂 ~ 2 = 6.467715.2TLR2rs3804100). There was no significant difference in the frequency of locus gene and C allele carrier between gastric cancer group and normal control group. The polymorphism of TLR4 rs10759932) gene was significantly correlated with the incidence of gastric cancer in Qingdao area. Carrying TC and CC genotypes can reduce the susceptibility of gastric cancer. The allele C may be a protective gene for gastric cancer. Carrying C allele can significantly reduce the risk of gastric cancer. There was no significant difference in the frequency of TLR9rs3809rs3809rs3809rs3804100TLR4rs11536889rs1075999rs1075999TLR9-1486TLR9-2848 gene polymorphism between the EBVn GC group and the EBVa GC group. There was no significant difference in the polymorphism of TLR9-1486TLR9-2848 gene between the EBVn GC group and the EBVa GC group (P0.05P > 0.05), and there was no significant difference in the polymorphism of TLR9-1486TLR9-2848 gene between the EBVn GC group and the EBVa GC group. The polymorphism of TLR2 rs3804099 gene may be related to the incidence of gastric cancer. The allele C may be a high risk gene for gastric cancer. Carrying C allele may increase the risk of gastric cancer. The polymorphism of TLR4 rs10759932 gene may be related to the incidence of gastric cancer. Carrying the C allele may reduce the attack rate of gastric cancer. TLR2TLR2ORs3804099 rs3804100 TLR4 rs11536889 rs10759932hp polymorphism and TLR9-2848 gene polymorphisms have no synergistic effect on EBV infection, and there is no correlation between TLR9-1486 polymorphism and susceptibility to EBVa GCC.There is no association between TLR9-1486 and TLR9-1486 gene polymorphisms, but no association between TLR9-1486 and TLR9-1486 gene polymorphism.
【学位授予单位】：青岛大学
【学位级别】：硕士
【学位授予年份】：2016
【分类号】：R735.2

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