Gastrin Plays a Significant Role in Helicobacter-Induced Stomach Cancer

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A study of the role of Helicobacter infection in the development of microbially induced gastric cancer has found that gastrin plays a key role in the development as well as the location of this disease.

Although it is well-established that Helicobacter infection results in increased expression of gastrin, the role of this hormone in cancer development has been unclear. High levels of gastrin lead to the development of stomach cancer, but the absence of gastrin has also been shown to increase the numbers of tumors in the gastric antrum.

To reconcile this apparent incongruity, a group led by Timothy C. Wang, MD, Professor of Medicine and Chief, Division of Digestive and Liver Disease at Columbia University Medical Center, studied Helicobacter infection and gastric cancer in transgenic animal models that expressed high levels of gastrin or were gastrin deficient. They found that Helicobacter infection in mice with high levels of gastrin resulted in cancer that localized to the gastric corpus, whereas infection in gastrin-deficient mice led to cancers in the gastric antrum. The study appears in the July 2009 issue of The American Journal of Pathology.

Based on these findings, Wang et al posit that gastrin may serve as a “rheostat” for the stomach. They note that gastrin likely plays a central role for protection against mucosal damage that can be caused by gastric acid secretion induced by gastrin itself; thus, either too much or too little gastrin could predispose a person to stomach cancer. Therefore, clinicians in the future may need to be cognizant of these effects before prescribing acid-suppressing drugs for long-term use in patients infected with Helicobacter, Wang says.

“These results demonstrate gastrin has a distinct effect on the gastric corpus and antrum in the setting of chronic gastric Helicobacter infection,” the authors state. “While gastrin is possibly an essential cofactor for gastric corpus carcinogenesis, gastrin deficiency can predispose animals to antral tumorigenesis, and thus any imbalances in gastrin physiology may represent a risk for gastric transformation. This study provides novel insights for the elucidation of the mechanism of Helicobacter-associated gastric cancer.”

See “Gastrin is an essential cofactor for helicobacter-associated gastric corpus carcinogenesis in C57BL/6 mice,” Am J Pathol 2009;175:365–375.