Toll样受体1基因多态性与胃癌癌前病变的相关性研究

发布时间：2018-10-09 21:11

【摘要】：背景:胃癌的发病率和死亡率高居全球第二位,在我国,胃癌更是以每年新发病例近百万的速度增加。大量研究表明,肠化生、细胞异型增生为胃癌的癌前病变。Toll样受体1(TLR1)基因多态性与多种疾病的发生相关,但与胃癌癌前病变关系的研究少见。目的:探讨TLR1基因rs4833095位点多态性与胃癌癌前病变的相关性,以期为阐明胃癌癌前病变的遗传机制提供依据。方法:选取2008年12月—2014年12月青岛市市立医院432例胃癌癌前病变患者(包括上皮内瘤变者84例、肠上皮化生者348例),同时以540名健康志愿者作为对照。采用DNA测序法检测TLR1基因rs4833095位点基因型,评估幽门螺杆菌(H.Pylori)感染状态。以多因素logistic回归模型调整年龄、性别、H.Pylori感染及吸烟因素后,分析TLR1基因多态性与胃癌癌前病变的关系。结果:病例组TLR1基因rs4833095位点GG、GA、AA基因型频率在病例组与对照组相比差异有统计学意义(χ2=19.966,P=O.000);病例组AA基因型频率明显高于对照组(17.6%比8.9%,χ2=16.336,P=0.000)。多因素logistic回归显示,以GG基因型为参照,携带AA基因型者胃癌的发病风险明显增加(OR=1.329,95%CI:1.002—1.762)。与GG+GA基因型且未感染H.Pylori的患者相比,携带AA基因型并感染H.Pylori者发生胃癌癌前病变的风险明显增加(OR=3.617,95%CI:2.147-6.092)。结论:TLR1 rs4833095基因多态性与胃癌癌前病变发病风险正相关。
[Abstract]:Background: the incidence and mortality of gastric cancer is the second highest in the world. In China, gastric cancer is increasing at the rate of nearly one million new cases every year. A large number of studies have shown that the polymorphism of Toll-like receptor 1 (TLR1) gene in precancerous lesions of gastric cancer is associated with intestinal metaplasia and cell dysplasia, but there are few studies on the relationship between the polymorphisms of Toll-like receptor 1 (TLR1) gene and precancerous lesions of gastric cancer. Objective: to investigate the association between rs4833095 polymorphism of TLR1 gene and precancerous lesions of gastric cancer, and to provide evidence for elucidating the genetic mechanism of precancerous lesions of gastric cancer. Methods: 432 patients with precancerous lesions of gastric cancer (including 84 cases of intraepithelial neoplasia and 348 cases of intestinal metaplasia) were selected from Qingdao Municipal Hospital from December 2008 to December 2014, and 540 healthy volunteers were used as control. The rs4833095 genotype of TLR1 gene was detected by DNA sequencing to evaluate the status of Helicobacter pylori (H.Pylori) infection. Multivariate logistic regression model was used to analyze the relationship between TLR1 gene polymorphism and precancerous lesions of gastric cancer after adjusting for age, sex, H. Pylori infection and smoking. Results: the frequency of GG,GA,AA genotype at rs4833095 locus of TLR1 gene in the case group was significantly higher than that in the control group (蠂 2 + 19.966 P0. 000), and the frequency of AA genotype in the case group was significantly higher than that in the control group (17. 6% vs 8. 9%, 蠂 2 + 16. 336% P0. 000). Multivariate logistic regression showed that the risk of gastric cancer with AA genotype was significantly increased (OR=1.329,95%CI:1.002-1.762) compared with GG genotype. Compared with patients with GG GA genotype and no H.Pylori infection, patients with AA genotype and H.Pylori infection had a significantly higher risk of precancerous lesions (OR=3.617,95%CI:2.147-6.092). Conclusion the rs4833095 polymorphism of TLR1 gene is positively associated with the risk of precancerous lesions of gastric cancer.
【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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