發(fā)布時間：2018-10-09 21:11

【摘要】：背景:胃癌的發(fā)病率和死亡率高居全球第二位,在我國,胃癌更是以每年新發(fā)病例近百萬的速度增加。大量研究表明,腸化生、細(xì)胞異型增生為胃癌的癌前病變。Toll樣受體1(TLR1)基因多態(tài)性與多種疾病的發(fā)生相關(guān),但與胃癌癌前病變關(guān)系的研究少見。目的:探討TLR1基因rs4833095位點多態(tài)性與胃癌癌前病變的相關(guān)性,以期為闡明胃癌癌前病變的遺傳機(jī)制提供依據(jù)。方法:選取2008年12月—2014年12月青島市市立醫(yī)院432例胃癌癌前病變患者(包括上皮內(nèi)瘤變者84例、腸上皮化生者348例),同時以540名健康志愿者作為對照。采用DNA測序法檢測TLR1基因rs4833095位點基因型,評估幽門螺桿菌(H.Pylori)感染狀態(tài)。以多因素logistic回歸模型調(diào)整年齡、性別、H.Pylori感染及吸煙因素后,分析TLR1基因多態(tài)性與胃癌癌前病變的關(guān)系。結(jié)果:病例組TLR1基因rs4833095位點GG、GA、AA基因型頻率在病例組與對照組相比差異有統(tǒng)計學(xué)意義(χ2=19.966,P=O.000);病例組AA基因型頻率明顯高于對照組(17.6%比8.9%,χ2=16.336,P=0.000)。多因素logistic回歸顯示,以GG基因型為參照,攜帶AA基因型者胃癌的發(fā)病風(fēng)險明顯增加(OR=1.329,95%CI:1.002—1.762)。與GG+GA基因型且未感染H.Pylori的患者相比,攜帶AA基因型并感染H.Pylori者發(fā)生胃癌癌前病變的風(fēng)險明顯增加(OR=3.617,95%CI:2.147-6.092)。結(jié)論:TLR1 rs4833095基因多態(tài)性與胃癌癌前病變發(fā)病風(fēng)險正相關(guān)。
[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.
【學(xué)位授予單位】：青島大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2016
【分類號】：R735.2

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