Chronic gastritis in a sample of the general population : Helicobacter pylori infection, metaplastic transformation, epithelial proliferation, p53- and p21 expression and antral mucosal gastrin content with reference to gastric carcinoma development

Abstract: Infection with H. pylori is the main cause of chronic inflammation in the stomach. lt is strongly associated with benign ulcer disease and a risk factor for gastric carcinoma (GC). Different tophographical types of gastritis bear different risks for future development of GC. Mucosal changes, atrophy and intestinal metaplasia (IM) are known precancerous conditions.The aims of this thesis were to map out the prevalence of chronic gastritis, including different tophographical types, carditis and H. pylori infection in an adult Swedish general population sample. To determine the prevalence of atrophy and different types of IM and measure the mucosal proliferative activity (Ki-67), expression of p53 and p21 with immunohistochemistry. Furthermore, to determine plasma levels of gastrin and the content of G-cells in the antrum with immunohistochemistry measured with three different morphometrical methods.The prevalence of chronic gastritis was 50%. lt was associated with H. pylori infection in 87%. The prevalence of carditis was 55% and it was associated with local H. pylori infection in 70%. The most common type of gastritis was antrum predominant (44%) followed by pangastritis (37%) and corpus predominant (19%). The prevalence of atrophy (antrum and/or corpus) was 55% and it increased with age, as did the prevalence of IM, which was present in the antrum or corpus in 23% and in the cardia in 10%. Corresponding figures for the prevalence of type III IM was 4% and 1%, repspectively. In all locations there was a strong correlation between the occurrence of IM and both H. pylori infection and chronic inflammation. Chronic inflammation and H. pylori infection were associated with increased mucosal proliferation and expression of p53. Atrophy as well as IM were associated with increased expression of p53 in both the corpus and antrum. IM was associated with increased proliferation in the mucosa, as was atrophy in the corpus. The expression of p21 was low and not affected by infection or inflammation. Plasma levels of gastrin were increased in subjects with H. pylori infection and showed no correlation with the amount of antral G-cells. The three different methods for G-cell quantification correlated poorly.In conclusion,chronic gastritis and carditis in this sample of an adult Swedish general population were frequent and strongly associated with H. pylori infection. The prevalences of different gastritis types and mucosal changes associated with increased cancer risk were determined and the relationships between chronic gastritis/carditis and both increased mucosal proliferation and expression of p53 in all parts of the stomach were established. Increased plasma levels of gastrin among subejects with H. pylori infection were established, as was the lack of a correlation between circulating gastrin levels and the amount of G-cells in the antrum. Poor correlations between three different methods for G-cell quantification highlight a methodological problem.