The effect of gender on Helicobacter pylori and gastric cancer

Gastric cancer is the 2 leading cause of cancer death worldwide and the 4 most commonly diagnosed cancer worldwide. Helicobacter pylori infection is the major risk factor of gastric cancer, and as such, this bacterium has been classified as a type 1, or definite, carcinogen by the International Agency for Research on Cancer. H. pylori infects the gastric mucosa of more than half of the world's population and promotes gastric carcinogenesis by inducing chronic inflammation. Over decades of persistent H. pylori infection and chronic inflammation, the stomach goes through a well characterized pathological progression involving chronic gastritis, atrophy, intestinal metaplasia, dysplasia, and ultimately cancer. Interestingly, there are strong gender differences in the development of gastric cancer, as men are twice as likely to develop the disease than women. Given the importance of H. pylori and chronic inflammation in gastric carcinogenesis, this thesis investigated the role of gender in modulating host immune responses to H. pylori. The aims of this thesis explored 1) the effect of gender on H. pylori’s ability to induce mutations and 2) the effect of estrogen and the anti-estrogen, Tamoxifen, on H. pyloriinduced gastric cancer. For the first aim, the gpt delta mouse model, a murine mutational analysis model, was used to study chronic infection with H. pylori. Increased frequency of point mutations was observed in infected female mice at 12 months post infection. These mutations