June 28, 2009 A group led by Columbia University Medical Center's Timothy Wang, M.D., has studied the role of Helicobacter infection in the development of stomach cancer and found that the hormone gastrin, which stimulates secretion of gastric acid, plays a key role in the development of Helicobacter-induced stomach cancer, and may have distinct effects on carcinogenesis in different parts of the stomach.
More than 50 percent of the world's population is infected with Helicobacter, which causes chronic inflammation of the stomach lining and is strongly linked to the development of gastric ulcers and stomach cancer. Stomach cancer is the second leading cause of cancer-related deaths worldwide.
Helicobacter infection results in increased expression of gastrin, although its role in cancer development has been unclear. High levels of gastrin lead to the development of stomach cancer, but absence of gastrin has been shown to increase the numbers of tumors in the gastric antrum, the lower section of the stomach that empties into the small intestine.
To reconcile this apparent incongruity, a group led by Dr. Wang studied Helicobacter infection and stomach cancer in animal models with either high expression of gastrin or no gastrin at all. They found that Helicobacter infection in mice with high levels of gastrin resulted in cancer of the gastric corpus (main body of the stomach), whereas infection in gastrin-deficient mice developed cancer in the gastric antrum.
Dr. Wang, with CUMC's Dr. Shigeo Takaishi, and their colleagues, argue that gastrin may serve as a "rheostat" for the stomach. Gastrin likely plays a central role in the safety network for the protection from mucosal damage caused by gastric acid secretion induced by gastrin itself, and thus either too much or too little gastrin could predispose a person to stomach cancer. Therefore, clinicians in the future may need to be more careful about prescribing acid-suppressive drugs for long-term use in patients infected with Helicobacter, Dr. Wang says.
In future studies, Dr. Wang and colleagues plan to study "host factors other than gastrin that are also important for Helicobacter-associated gastric carcinogenesis." These include specific cytokines and chemokines induced by Helicobacter infection and modulated by gastrin, that link inflammation and cancer. In addition, they plan to study the role of other non-Helicobacter bacteria that colonize the stomach when acid secretion is suppressed, since bacterial overgrowth likely contributes to gastric carcinogenesis.
The work was supported by grants from the National Institutes of Health, the Medical Research Council, the Welcome Trust and the Wolfson Foundation.
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- Takaishi S, Tu S, Dubeykovskaya ZA, Whary MT, Muthupalani S, Rickman BH, Rogers AB, Lertkowit N, Varro A, Fox JG, Wang TC. Gastrin is an essential cofactor for Helicobacter-associated gastric corpus carcinogenesis in C57BL/6 mice. Am J Pathol, 2009 175: 2775-2786
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