hOGG1基因遗传变异与胃癌发病风险及化疗敏感性研究

胃癌是中国常见的消化道肿瘤之一，其发病机制仍然不是十分清楚。研究发现DNA修复基因hOGG1基因的遗传变异能够改变DNA修复能力，与个体罹患肿瘤的易感性有关。本课题组前期已经发现hOGG1基因的Ser326Cys多态性能够增加胃癌的发病风险，为了进一步明确hOGG1基因多态性与胃癌易感性的关系，本课题将通过数据库筛选hOGG1基因所有的多态性位点，利用胃癌病例-对照和单纯病例方法分析hOGG1基因多态性与胃癌的发病风险和铂类药物化疗敏感性关系。在此基础上，采用MTT、细胞侵袭、流式细胞仪、RT-PCR和Western-blot等方法验证多态性与化疗敏感性的生物学机制，最终为探索胃癌的发病机制和个体化治疗提供理论依据。

Gastric cancer is one of the most common cancers of digestive tract in China. However, the etiology of gastric cancer is still unknown. Many studies have found that genetic variants in DNA repair gene hOGG1 could impact the DNA repair capacity, which were susceptibly to cancer risk. In our previous study, we found that the hOGG1 Ser326Cys polymorphism was associated with increased risk of gastric cancer. Here, in order to investigate the association with risk of gastric cancer, we will first select all the SNPs in the hOGG1 genes. Further, we will detect the association between hOGG1 SNPs and gastric cancer risk and platinum-based chemotherapy sensitivity. On the basis of these results, we will assess the mechanism of chemotherapy sensitivity by MTT, cell invasion, flow cytometry, RT-PCR, and Western-blot, and other assays. Our results would provide a theoretical basis for exploring the mechanism and individual treatment for gastric cancer.