New concepts in GastroenterologyInflammation, Atrophy, Gastric Cancer: Connecting the Molecular Dots
Section snippets
Location, Location, Location
About 60% to 80% of intestinal-type cancers arise from the gastric antrum with a preference for the lesser curvature. The gastric epithelium is not homogenous but, in fact, is divided into 3 distinct regions, the (upper) cardia, (middle) corpus, and (lower) antrum, with the transitional zone from the oxyntic to antral glands occurring at the incisura. Although many older cancer registries did not distinguish between these locations, it has become more apparent that classification of the cancer
Environmental Triggers: Inflammation Versus Bacteria
The dramatic decline in gastric cancer during the past century correlating with improvements in food storage has placed the etiologic focus squarely on environmental factors.1, 9 Ingestion of a high-salt diet, smoked foods rich in nitrates, and contaminated water teeming with H pylori appear to be the major environmental inducers of gastric cancer, but for different reasons. High salt disrupts the gastric mucosal barrier,9 while N-nitroso mutagens formed from dietary nitrates by bacteria
Connecting the Molecular Dots
Numerous genes have already been implicated in gastric transformation. However, an essential question that emerges is how to organize the known alterations into a temporal sequence of events. The earliest alterations in the gastric mucosa invariably involve epigenetic changes, eg, hypermethylation.12 Although the mechanism by which inflammation stimulates DNA methyltransferases has not been widely pursued, apparently nitric oxide can stimulate the activity of these enzymes that in turn mediate
References (14)
- et al.
Focus on gastric cancer
Cancer Cell
(2004) beta-Catenina pivot between cell adhesion and Wnt signalling
Curr Biol
(2005)- et al.
Synergistic interaction between hypergastrinemia and Helicobacter infection in a mouse model of gastric cancer
Gastroenterology
(2000) - et al.
Interferon gamma induction of gastric mucous neck cell hypertrophy
Lab Invest
(2005) - et al.
Aberrant CpG island hypermethylation of chronic gastritis, in relation to aging, gender, intestinal metaplasia, and chronic inflammation
Am J Pathol
(2003) - et al.
Influence of site classification on cancer incidence ratesan analysis of gastric cardia carcinomas
J Natl Cancer Inst
(2004) - et al.
Helicobacter pylori infection and gastric atrophyrisk of adenocarcinoma and squamous-cell carcinoma of the esophagus and adenocarcinoma of the gastric cardia
J Natl Cancer Inst
(2004)
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Grants R01-DK45729, R01-DK61410, and P01-DK062041 from the National Institutes of Health provided funding. I would like to thank Linda Samuelson and Weiqun Kang for helpful comments.