【作者】 张丽；

【导师】 魏莎莉； 刘纯杰；

【作者基本信息】 重庆医科大学 ， 遗传学， 2011， 硕士

【摘要】 目的:探讨中国汉族人群基因单核苷酸多态性与H.pylori感染引起胃癌发生的关联性。方法:采用病例对照研究的方法,收集了296例胃癌患者(病例组)和160例胃炎患者(对照组)。采用酶联免疫吸附实验检测血清中的抗H.pylori IgG抗体来确定受试者的H.pylori感染情况。使用Sequenom MassArray系统对PTPN11、NOD1、NOD2、CD14、TLR4、TLR9基因的TagSNPs进行基因分型。采用PCR-RFLP的方法,对中国汉族的268例胃癌(病例组)、190例慢性胃炎(对照组)患者的P53Arg72Pro和MDM2 SNP T309G的基因多态性位点进行了基因分型。结果:中国汉族人群单核苷酸多态性与胃癌发生的相关性1. P53 Arg72Pro和MDM2 SNPT309G与胃癌发生风险不具有相关性。2. PTPN11基因第3内含子rs2301756位点SNP与胃癌的发病风险无关联性,该位点的多态性与H. pylori感染阳性胃癌的发生风险无相关性。3.NOD1和NOD2基因多态性与胃癌发生的相关性3.1. NOD1 rs2907749 GG基因型能降低胃癌的发生风险(调整后的OR0.50; 95% CI 0.26-0.95)而rs7789045 TT基因型能增加胃癌的风险(OR 2.14; 95%CI 1.20-3.82)。3.2在H.pylori感染阳性的人群中,NOD1 rs7789045 TT能增加胃癌的发生风险(OR 2.05; 95%CI 1.07-3.94),并且NOD2 rs7205423 GC基因型(调整后OR 2.52; 95%CI 1.05-6.04)也能增加胃癌的发生风险。3.3单体型分析显示,NOD1基因的AGT单体型(由顺序排列的rs2907749, rs2075820和rs7789045构成)在病例组和对照组中的分布有显著性的差别(校正后P: 0.04)。4.TLR4基因多态性与胃癌发生的相关性TLR4的rs2149356等位基因多态性位点的杂合子基因型显著性的增加了胃癌的发生风险(经过调整后OR,1.55; 95%CI, 1.02-2.36; P= 0.042)。rs7873784位点的隐性模型(CCvs. CG+GG)也显著性的增加了胃癌的发生风险(经过调整后OR分别为: OR,1.85; 95%CI, 1.01-3.37; P= 0.046和OR, 1.88; 95%CI, 1.03-3.43; P= 0.039)。5.CD14基因多态性与胃癌发生的相关性5.1 CD14的rs2569190 GA显性模型( GG+GA vs. AA)显著性降低了胃癌的发生风险(调整后分别为OR,0.64; 95%CI, 0.42-0.98 P=0.041;OR,0.64; 95%CI, 0.43-0.96 P=0.032)。5.2 CD14基因的rs2563298,rs2569190,rs5744441构成3个单体型(CAC、CGT、AGC)。最常见的单体型是CAC,其在病例组和对照组人群有显著性的分布差异(P=0.048)。结论:中国汉族人群P53 Arg 72Pro、MDM2 SNPT309G、PTPN11基因第3内含子rs2301756位点SNP不能影响胃癌的发病风险,这些位点的多态性与H. pylori感染阳性胃癌的发生风险无相关性。NOD1、NOD2、TLR4、CD14基因多态性可能与H.pylori相互作用,并且在中国汉族人群胃癌的发生中起着重要的作用。更多还原

【Abstract】 Background:This study examined single nucleotide polymorphisms and their associations with the risk of developing gastric cancer in relation to Helicobacter pylori infection in Chinese han population.Methods:We conducted a hospital-based case–control study including 296 incident gastric cancer patients and 160 gastritis controls. TagSNPs in PTPN11,NOD1,NOD2,CD14,TLR4,TLR9 genes were genotyped by using Sequenom MassArray system. Serum levels of anti-H.pylori IgG were measured by enzyme-linked immunosorbent assay to indicate H.pylori infection. PCR-RFLP was also applied in genotyping P53Arg72Pro and MDM2 SNP T309G in 268 patients with gastric cancer , and 190 gender-age-matched chronic gastritis patients served as controls.Results:1. P53 Arg 72Pro and MDM2 SNPT309G are not associated the risk of gastric cancer.2. PTPN11 G/A polymorphism at intron 3 could not infect the risk of gastric cancer. PTPN11 polymorphism was not associated with H.Pylori infection states in both cancer patients and controls.3. The association of NOD1 and NOD2 polymorphisms and gastric cancer3.1 NOD1 rs2907749 GG genotype gene showed a decreased risk for gastric cancer [adjusted odds ratio (OR) 0.50; 95% confidence interval (CI) 0.26-0.95] while rs7789045 TT genotype showed an increased risk for gastric cancer (OR 2.14; 95%CI 1.20-3.82).3.2 An elevated risk of gastric cancer was observed in subjects with H.pylori infection and NOD1 rs7789045 TT genotype (OR 2.05; 95%CI 1.07-3.94) or NOD2 rs7205423 GC genotype (OR 2.52; 95%CI 1.05-6.04).3.3 Haplotype analysis suggested that the distribution of AGT (indicated as in the order of rs2907749, rs2075820 and rs7789045) in NOD1 between cases and control groups was significantly different (Pcorrected: 0.04).4. the association of TLR4 polymorphisms and gastric cancerTLR4 rs2149356 AC heterozygote genotype showed an elevated risk for gastric cancer (adjusted OR,1.55; 95%CI, 1.02-2.36; P= 0.042).An elevated risk for gastric cancer also was observed in subjects with rs7873784 CG heterozygote genotype and the recessive model (genotype CCvs. CG+GG) (adjusted OR,1.85; 95%CI, 1.01-3.37; P= 0.046 and OR, 1.88; 95%CI, 1.03-3.43; P= 0.039,respectively).5. the association of CD14 polymorphisms and gastric cancer5.1 CD14 rs2569190 the dominant model (GG+GA vs. AA)significantly decreased the risk of gastric cancer (adjusted OR,0.64; 95%CI,0.42-0.98 P=0.041;OR,0.64; 95%CI, 0.43-0.96 P=0.032,respectively).5.2 rs2563298,rs2569190,rs5744441 in CD14 constructed three haplotypes(CAC、CGT、AGC),The most common haplotype was CAC and the distribution was significantly different between cases and controls (P=0.048).Conclusions: P53 Arg 72Pro,MDM2 SNPT309G and PTPN11 G/A polymorphism at intron 3 could not infect the risk of gastric cancer. PTPN11 polymorphism was not associated with H.Pylori infection states in both cancer patients and controls.Genetic polymorphisms in NOD1,NOD2,TLR4,CD14 may interaction with H.pylori infection and may play important roles in developing gastric cancer in the Chinese population.更多还原