【作者】 肖献秋；

【导师】 龚伟达；

【作者基本信息】 江苏大学 ， 外科学， 2010， 硕士

【摘要】 研究目的:在江苏省宜兴市进行以人群为基础的分子流行病学病例-对照研究,筛选错配修复基因hMLH1和hMSH2有功能意义的4个SNPs,探讨hMLH1和hMSH2基因突变与我国胃癌发生风险的关联性。最终为阐明胃癌发病的分子遗传学机制,指导高危人群有针对性的预防和治疗提供依据。研究方法:以江苏省宜兴市554例胃癌患者和592例年龄(±5岁)、性别相匹配的非胃癌患者(对照组)作为研究对象,用TaqMan MGB探针对hMLH1基因-93G＞A、1219V和hMSH2基因-118T＞C、IVS12-6T＞C四个SNPs进行基因分型,χ2检验比较研究人群年龄、性别、吸烟、饮酒等因素频数分布差异,揭示胃癌发生与吸烟、饮酒等生活习惯之间的关系。非条件Logistic回归分析不同基因型与胃癌发生风险的关联性。分层分析探讨不同基因型与胃癌发生的性别、年龄、吸烟、饮酒及其临床病理特征之间的关联性。结果:1,胃癌病例中吸烟、饮酒者多于对照组,和对照组相比有显著性差异(P＜0.001和P=0.002)。2,在病例-对照研究中我们发现hMLH1基因-93G＞A、1219V和hMSH2基因-118T＞C、IVS12-6T＞C四个SNPs与胃癌的发生风险无显著关联性(P＞0.05)。分层分析我们发现hMSH2基因-118T＞C合并突变基因型(TC+CC)和对照相比与年轻人群(年龄≤63岁)胃癌和弥漫型胃癌的发生风险有显著关联性(调整OR=1.51,95%CI=1.05-2.16和调整OR=1.41,95%CI=1.01-1.96)。而其余三个SNPs尚未发现此种关联性。结论:1,胃癌的发生是复杂的,多因素的,有许多已知的因素参与了胃癌的发生,如吸烟、饮酒等因素。2,错配修复基因hMLH1-93G＞A、I219V和hMSH2IVS12-6T＞C多态可能与胃癌的发生风险无显著关联性。3,hMSH2-118T＞C多态可增加年轻人群胃癌和弥漫型胃癌的发生风险。更多还原

【Abstract】 Objective:Population-based case-control study on molecular epidemiology was carried out in Yixing city, which in the Jiangsu Province of China. To assess the association between the mismatch repair genes hMLH1 and hMSH2 polymorphisms and the risk of gastric cancer in China, four polymorphic sites with functional significance of hMLH1 and hMSH2 genes were selected. In the end the mechanism of the molecular genetics which lead to the incidence of gastric cancer will be clarified. Furthermore, this study will guide the prevention and therapy for high-risk groups.Methods:554 patients with gastric cancer cases and 592 cancer-free controls frequency-matched by age (±5) and sex were recruited in the study. The genotypes of the hMLH1-93G>A, I219V and hMSH2-118T>C, IVS12-6T>C polymorphisms were detected by TaqMan MGB probe method. Chi-square test was used to evaluate differences in frequency distributions of age, sex, smoking status and alcohol use between the cases and controls and further to assess the association with the occurrence of gastric cancer. Unconditional logistic regression was used to assess the association between each polymorphism and gastric cancer. We further analyzed the interaction of age, sex, smoking, alcohol use and tumor clinic pathological characteristics.Results: 1. Gastric cancer cases have more smokers and drinkers than controls and the association between them was statistically significant (P < 0.001 and P = 0.002, respectively).2. No evidence of an association between any of the four polymorphisms and gastric cancer was observed (P > 0.05) . Further analysis revealed that, when compared with the control populations, the hMSH2-118 combined variant genotypes (TC+CC) were increased the risk of gastric cancer accompanied with younger subjects (age≤63 years; adjusted odds ratios [OR] = 1.51, 95% confidence intervals [CI] = 1.05-2.16) and associated with diffuse-type tumors (adjusted OR =1.41, 95% CI = 1.01-1.96).Conclusion:1. Gastric cancer is a complex and multifactorial process. There are many known factors involved in the occurrence of gastric cancer, such as smoking and alcohol use.2. The hMLH1-93G>A, I219V and hMSH2 IVS12-6T>C polymorphisms may not contribute to risk of gastric cancer.3. The hMSH2-118T>C polymorphism may confer not only an increased risk of younger subjects (age≤63 years) of gastric cancer but also with diffuse-type tumors.更多还原