We conducted a longitudinal cohort study to determine the association of Helicobacter pylori
infection and the progression of chronic
atrophic gastritis (CAG) with
gastric cancer. A cohort of 4655 healthy asymptomatic subjects was followed for a mean period of 7.7 years. H. pylori
infection was established by serum specific
antibodies and the presence of CAG was confirmed by serum
pepsinogen. During the follow-up period, 45
gastric cancer cases were detected (incidence rate, 126/100000 person-years). A univariate analysis after adjustment for age showed that both H. pylori and CAG were significantly associated with
gastric cancer. To clarify the interaction between H. pylori and CAG, an analysis stratified by H. pylori- and CAG-status was performed. No
cancer developed in the H. pylori(-)/CAG(-) group during the study period. This supports the theory that it is quite rare for any type of
gastric cancer to develop in an H. pylori-free healthy stomach. With the progression of H. pylori-induced
gastritis, the risk of
gastric cancer increased in a stepwise fashion from CAG-free
gastritis [H. pylori(+)/CAG(-) group] (HR=7.13, 95%CI=0.95-53.33) to CAG [H. pylori(+)/CAG(+) group] (HR=14.85, 95%CI=1.96-107.7) and finally to severe CAG with extensive intestinal
metaplasia [H. pylori(-)/CAG(+) group] (HR=61.85, 95%CI=5.6-682.64) in which loss of H. pylori from the stomach is observed. Therefore, it is probable that H. pylori alone is not directly associated with stomach
carcinogenesis. Instead, H. pylori appears to influence stomach
carcinogenesis through the development of CAG. The observed positive correlation between the extent of H. pylori-induced
gastritis and the development of
cancer was strong, especially for the intestinal type. These results are compelling evidence that severe
gastritis with extensive intestinal
metaplasia is a major risk factor for
gastric cancer, and they confirm the previously described model of stomach
carcinogenesis: the
gastritis-
metaplasia-
carcinoma sequence.