Gastric Cancer Bacteria Cause
Numerous epidemiologic studies have shown that a diet high in salt is associated with an increased risk of gastric cancer. Now Timothy L. Cover and colleagues of Vanderbilt University show that high dietary salt combined with infection by the ulcer-causing bacterium Helicobacter pylori greatly increases the risk of cancer. The study was published ahead of print in the journal Infection and Immunity. Stomach cancer, or gastric cancer, refers to cancer arising from any part of the stomach. Stomach cancer causes about 800,000 deaths worldwide per year. In the study, the researchers infected Mongolian gerbils with H. pylori. One set of gerbils received a regular diet; the other, a high salt diet. At the end of the experiment the researchers analyzed the animals' stomach tissues. Every animal on the high salt diet developed cancer, compared with just 58 percent of those on the regular diet. It appears development of gastric cancer required the presence of a particular bacterial oncoprotein, known as CagA, which is produced by H. pylori. Gastric cancer did not develop in animals on the high salt diet that were infected with a mutant H. pylori which did not produce CagA.
It appears that development of gastric cancer required the presence of a particular bacterial oncoprotein, known as CagA, which is produced by H. pylori. Gastric cancer did not develop in animals on the high salt diet that were infected with a mutant H. pylori which did not produce CagA. In earlier studies, Cover and others had shown that culturing H. pylori in a high salt environment boosts production of CagA.
CagA is a 120-145kDa protein encoded on the 40kb cag pathogenicity island. H. pylori strains can be divided into CagA positive or negative strains, of which around 60% of H. pylori isolates in Western countries are positive, whereas the majority of East Asian isolates are negative.
"This was one of the driving forces that led us to undertake the current studies," says Cover. The investigators note that while no studies, to their knowledge, have examined relationships among a high salt diet, and infection with H. pylori expressing cagA, "in several parts of the world that have high rates of gastric cancer, there is a high prevalence of cagA+ strains and a large proportion of the population consumes a high-salt diet."
The investigators also detected significantly higher levels of gastric inflammation in H. pylori-infected gerbils on a high salt diet than in those on a regular diet, a finding which Cover says is relevant to many types of cancer. They also showed that transcription of various inflammatory cytokines, such as interleukin 1-beta, are elevated in the former as compared to the latter, suggesting that "these factors may contribute to the increased inflammation and increased gastric risk that accompany a high salt diet," says Cover.
H. pylori is a Gram-negative, microaerophilic bacterium found in the stomach. It was identified in 1982 by Barry Marshall and Robin Warren, who found that it was present in patients with chronic gastritis and gastric ulcers, conditions that were not previously believed to have a microbial cause. It is also linked to the development of duodenal ulcers and stomach cancer. However, over 80 percent of individuals infected with the bacterium are asymptomatic and it has been postulated that it may play an important role in the natural stomach ecology.[
For further information see Article or Gastric Bacteria.
Stomach Cancer image via Wikipedia.