甲硫氨酸合成酶还原酶（MTRR）是叶酸代谢途径中关建酶之一。叶酸代谢途径的损坏会影响核DNA和线粒体DNA的甲基化。细胞核或者线粒体DNA改变，会引起线粒体功能紊乱，进而引发复杂的细胞重新编程促进肿瘤的形成和生长。本项目组前期研究发现MTRR Ile22Met与胃癌发病风险相关。但至今为止未见文献报导MTRR Ile22Met多态性在胃癌中的功能研究。本项目组基于以往在胃癌研究方面的研究基础和经验，拟进行以下研究：（1）通过检测胃癌临床组织标本MTRR表达水平（蛋白、RNA表达水平），验证MTRR Ile22Met 多态性在胃癌发生和发展过程中的功能；（2）通过建立MTRR Ile22（野生型）、Met22（突变体型）细胞系，明确MTRR Ile22Met多态性对细胞生物学行为的影响；（3）探索MTRR Ile22Met多态性对于细胞线粒体DNA稳定性的影响，并探讨由此引发的胃癌发病机制。

Methionine synthase reductase (MTRR) is one of the key enzymes in folate metabolism. Accumulated evidences have proved that MTRR Ile22Met polymorphism was associated with cancer risk. We found that MTRR Ile22Met polymorphism was associated with gastric cancer risk. However, there is few functional research of MTRR Ile22Met polymorphism in gastric cancer. Therefore, further research is prepared as followed: (1) to assess the association and function of MTRR Ile22Met polymorphism in the gastric cancer, the expression and location of MTRR will be detected in the gastric cancer tissue specimens and cells; (2) to clarify the effect of MTRR Ile22Met polymorphism on cell behavior, cell lines contained MTRR Ile22 (wild type) amd Met22 (risk type) were established, respectively. (3) to further evaluate the mitochondria DNA stability involved in the cell behavior affected by the f MTRR Ile22Met polymorphism, both the animal models and cell models for epithelial cell cancer research were established and analysed.