Although chronic Helicobacter pylori infection is the strongest known risk factor for development of gastric adenocarcinoma, only a small proportion of infected individuals will ever develop tumours. This article discusses various bacterial, host and environmental factors which may influence an individual's susceptibility.
Recent research on bacterial virulence factors has focussed upon the cag pathogenicity island, particularly its roles in regulating epithelial growth and adhesion. Studies of host genetic factors have included several analyses of polymorphisms in inflammatory cytokines in human cohorts. Animal studies have recently clarified the roles of dysregulated epithelial apoptosis, proliferation and differentiation pathways during gastric carcinogenesis, and novel experiments involving H. felis infection of bone marrow transplanted irradiated mice have suggested that gastric cancer may originate from bone marrow-derived stem cells. Important roles for signalling between epithelial and mesenchymal cells, particularly myofibroblasts, are also emerging. Recent research on the importance of environmental factors has demonstrated how helminth coinfection may protect against atrophic gastritis and T helper type 1 responses.
Complex interactions between several bacterial, host genetic and environmental factors determine whether H. pylori infected individuals develop gastric carcinoma. The importance of bone marrow stem cell engraftment during human gastric neoplasia is an area requiring urgent investigation.
aDivision of Gastroenterology, University of Liverpool, Liverpool, UK
bLeeds Institute of Molecular Medicine, St James's University Hospital, Leeds, UK
Correspondence to Mark Pritchard, Division of Gastroenterology, 5th Floor UCD Building, University of Liverpool, Daulby St., Liverpool L39 3GA, UK Tel: +44 151 794 5772; fax: +44 151 794 6825; e-mail: firstname.lastname@example.org
D.M.P. is funded by a Wellcome Trust Advanced Fellowship for clinicians. J.E.C. is funded by Yorkshire Cancer Research and the Sixth Research Framework Programme of the European Union, Project INCA.