Some strains of a common bacterium harbor a gene that may underlie a huge share of stomach cancers, a new study finds.
The bacterium, Helicobacter pylori, has been linked to gastritis, ulcers, and stomach cancer. But while H. pylori infects, by some estimates, more than half the global population, there are only about a million people worldwide with stomach cancer. Apparently, therefore, not all strains of the microbe have malignant potential. Over the past decade, scientists have traced this discrepancy to H. pylori ‘s genetic makeup (SN: 11/30/02, p. 341). In particular, they’ve zeroed in on strains that carry a gene dubbed cagA, for cytotoxin-associated gene.
In the new study, researchers obtained frozen tissue samples snipped from the stomach linings of 2,145 people participating in a cancer-screening program in Venezuela. The samples revealed that 16 percent of the volunteers didn’t have an H. pylori infection. Of the 84 percent with H. pylori, roughly half had a strain that harbored cagA.
By coordinating these data with those from other tests on the volunteers, the researchers found that people with H. pylori carrying cagA were 16 times as likely to have dangerous premalignant stomach growths as were people with H. pylori lacking the rogue gene or with no H. pylori infection at all. The researchers report the findings in the Sept. 5 Journal of the National Cancer Institute.
“Our results show that it matters what kind of H. pylori a person has,” says study coauthor Ikuko Kato, a cancer epidemiologist at Wayne State University in Detroit. “It affects the risk of developing these precancerous lesions.” People with these lesions, called dysplasias, are up to 100 times as likely to develop stomach cancer as are people without them, she says.
“This is the kind of work that needs to be done … in populations at high risk of gastric cancer,” says Martin J. Blaser, a physician and molecular biologist at the New York University Medical Center. Recent estimates attribute two-thirds of all stomach cancer to H. pylori infections.
Blaser, whose research team discovered cagA in the early 1990s, estimates that roughly 60 percent of H. pylori infections in the United States and 80 percent in China are caused by microbes harboring cagA.
Past studies have established that cagA is part of a group of genes that encode proteins that make a “molecular syringe” that injects the microbe’s compounds into the cells of the stomach lining, Blaser says. These injected bacterial products change internal signaling in the cells.
This change could have multiple and complex effects, he says. For example, cagA-positive H. pylori may suppress stomach-acid production.
Stomach cancer rates have been declining in industrialized countries, possibly as the result of high use of antibiotics that cure H. pylori infections. Meanwhile, the prevalence of reflux disease and related cancer of the esophagus is increasing in those countries, Blaser says.
That more people are living longer without the microbe might explain these increases, Blaser hypothesizes. So wiping out the infection might solve one problem while creating another.