When it comes to the microbes that inhabit the gastrointestinal tract, one person’s poison may be another’s cure. Heliobacter pylori, the bacterium that causes gastric ulcers and stomach cancer in some people, may actually protect against cancer of the esophagus. A new study by researchers at the Oregon Health and Science University in Portland is shedding some light on this baffling paradox. From the Genome News Network:Pylori Paradox: Microbe Harms Stomach But Protects Esophagus
By Nancy Touchette
April 4, 2003
When it comes to the microbes that inhabit the gastrointestinal tract, one person’s poison may be another’s cure. Heliobacter pylori, the bacterium that causes gastric ulcers and stomach cancer in some people, may actually protect against cancer of the esophagus.
A new study by researchers at the Oregon Health and Science University in Portland is shedding some light on this baffling paradox.
Michael J. Rutten and Andrew D. Jones have found that certain strains of H. pylori can trigger the death of cancerous esophageal cells in culture. But these strains do not kill normal esophageal cells.
Thus, the bacteria appear to protect against cancer by killing off cancer cells and preventing their continuing growth and spread.
“These may not be such bad bugs after all,” says Rutten. “At least for the esophagus, H. pylori may have a protective effect in the development of cancer.”
Gastric cancer, or cancer of the stomach, is the second leading cause of death due to cancer in the world. During the past twenty years, dozens of studies have concluded that H. pylori is the primary culprit in causing peptic ulcers, non-Hodgkins lymphoma of the stomach, and gastric adenocarcinoma, or stomach cancer.
More than half of people throughout the world harbor H. pylori, which is usually contracted in childhood. For the most part the bacterium is the sole inhabitant in the hostile environment of the stomach.
Although large numbers of people have H. pylori in their stomachs, very few ever develop malignancy due to the organism. Researchers believe this is largely because of the existence of different strains of the bacteria, only some of which are harmful.
Studies by Martin J. Blaser of the New York University School of Medicine and others have shown that strains of bacteria that produce a protein known as CagA are particularly harmful in triggering stomach ulcers and cancer. And it is those same strains of cagA+ bacteria that are most protective against esophageal cancer.
A few years ago Blaser noticed from epidemiological studies that while the rate of H. pylori infection and that of stomach cancer over the past several years were decreasing, the rate of esophageal cancer was on the rise. Blaser attributes this to the widespread use of antibiotics that are killing H. pylori.
“Esophageal cancer is the fastest increasing cancer in the United States today,” says Blaser. “It is increasing at the rate of 8-9 percent each year all over the developed world. I predict that if it goes unchecked it will become the predominant cancer of this century.”
Esophageal cancer is usually preceded by acid reflux disease and a pre-cancerous condition known as Barrett’s esophagus, in which the cells of the esophagus grow abnormally.
Blaser’s observations prompted Rutten to ask whether H. pylori might be activating different biochemical pathways in the cells it encounters. In stomach cells, H. pylori, particularly those strains with the CagA protein, trigger the production of cytokines, chemical messengers that trigger inflammation and cell proliferation. Both may contribute to the harmful effects of H. pylori.
A complex system of proteins docks with the host cell to inject the CagA protein, which acts as a toxin inside the cell. Without CagA and its associated complex, the bacteria are relatively harmless.
Rutten found that H. pylori strains with the CagA protein induce esophageal cancer cells to die through apoptosis, a process of programmed cell death. Bacterial strains without the CagA protein had little effect in inducing the death of the cancer cells. “The bacteria with the CagA protein are the most likely to cause ulcers and stomach cancer,” says Rutten. “But the same bacteria are also the most likely to protect against esophageal cancer by triggering the death of proliferating cancer cells.”
The implications of the research are unclear, and researchers are not quite sure how to handle the new findings. Doctors frequently prescribe antibiotics to cure ulcers caused by H. pylori, but as the new research shows, this may increase the risk of esophageal cancer.
“It’s a tough issue,” says Rutten. “How do you treat patients? Do you take care of the problem at hand, knowing this may increase the risk of another cancer? We don’t really know.”
See related GNN article
?Life on the Inside: Surveying the diversity of H. pylori genomes in one man’s stomach
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Jones, A.D. et al. Heliobacter pylori induces apoptosis in Barrett’s-derived esophageal adenocarcinoma cells. J. Gastrointest. Surg. 7, 68-76 (2003).