Review article: exploring the link between Helicobacter pylori and gastric cancer

Cancer of the distal stomach, both of the intestinal and diffuse type, is strongly associated with Helicobacter pylori colonization. This bacterium causes chronic active inflammation of the gastric mucosa in the majority of colonized subjects. In a considerable number of them, this will eventually lead to a loss of gastric glands, and thus the establishment of atrophic gastritis, which is associated with the development of intestinal metaplasia and dysplasia. Development of atrophy and metaplasia of the gastric mucosa are thus strongly associated with H. pylori infection, instead of a direct and inevitable consequence of ageing. Approximately 40-50% of infected subjects develop these conditions, but they are rare in non-infected subjects. The presence of these consecutive disorders leads to a 5-90-fold increased risk for cancer of the distal stomach, in particular of the intestinal type. This sequence explains the increased risk for gastric cancer in H. pylori-infected subjects, as has been shown in various cross-sectional and longitudinal studies. In a combined analysis of three longitudinal studies, a significant trend was observed towards an increased odds ratio with longer intervals between (retrospective) serological diagnosis of H. pylori infection and observation of gastric cancer, this risk being more than eight-fold increased if the interval had been at least 15 years. This is thought to reflect development of atrophic gastritis and intestinal metaplasia with loss of H. pylori colonization in the years prior to development of cancer. Atrophic gastritis and gastric cancer thus appear closely associated with the presence of H. pylori, yet not all infected subjects will eventually develop atrophy and only a small minority develop gastric cancer. Factors that influence the risks for atrophy and cancer in the presence of infection may be related to the time that infection occurred and to characteristics of the bacterial strain and the host. Evidence for the role of these factors is now increasing. Recognition of the causal role of H. pylori in the induction of gastric cancer theoretically presents tools for cancer prevention. The efficacy of screening and bacterial eradication for prevention of distal gastric cancer is being studied in a number of large-scale intervention studies in different populations. It is hoped that these studies will also provide answers to the potential preventive role of H. pylori colonization in the development of gastro-oesophageal reflux disease and associated conditions, in particular development of cancer of the proximal stomach. Infection with H. pylori plays an important role in the aetiology of atrophic gastritis and gastric cancer. Studies suggest an eight-fold increased risk for both conditions in the presence of infection. Factors that influence the risk for both conditions in the presence of infection are the age at which infection occurred and the presence of cagA as a marker for more pathogenetic H. pylori strains. The efficacy and side-effects of intervention for the prevention of distal gastric cancer has yet to be established.