| Theme |
Risk Factors and Prevention of Gastric Cancer |
| Title |
Mechanism for H.pylori-induced Carcinogenesis |
| Author |
Tsutomu Chiba |
Department of Gastroenterology and Hepatology, Graduate School of Medicine, Kyoto University |
| Author |
Hiroyuki Marusawa |
Department of Gastroenterology and Hepatology, Graduate School of Medicine, Kyoto University |
| Author |
Yuko Matsumoto |
Department of Gastroenterology and Hepatology, Graduate School of Medicine, Kyoto University |
| [ Summary ] |
Helicobacter pylori (H. pylori) infection is the most important risk factor for gastric cancer development. Gastric cancer development is associated with the accumulation of various gene mutations, including the p 53 gene. However, the mechanism by which H. pylori induces gene mutations in the gastric mucosa remains unclear. Activation-induced cytidine deaminase (AID) is exclusively present in B lymphocytes and plays a crucial role in somatic hypermutation of immunoglobulin genes under physiological conditions. Interestingly, AID transgenic mice develop various cancers including gastric cancer, suggesting involvement of AID in gastric cancer development by inducing various gene mutations in AID transgenic mice. We found strong expression of AID in H. pylori infected gastritis mucosa as well as gastric cancer. Moreover, H. pylori infection of human gastric mucosal cells in vitro induces AID expression through NF-kappaB-dependent pathways. H. pylori-induced p 53 gene mutation is blocked by inhibition of AID. These data suggest that H. pylori infection induces AID expression through NF-kappaB activation in the gastric mucosa, resulting in various gene mutations, leading to gastric cancer development. |