Gene May Explain Why Some Have Higher Stomach Cancer Risk

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March 22, 2000 (Ithaca, N.Y.) -- People who become infected with the bacterium Helicobactor pylori are at higher risk for either ulcers or stomach cancer -- but not both, according to a study in this week's issue of Nature. Emad M. El-Omar, MD, and researchers at the National Cancer Institute have identified a gene that partly accounts for this either/or situation.

El-Omar tells WebMD that people who are infected with the bacterium and who also have this gene produce large amounts of an immune signal called "interleukin-1-beta." This causes inflammation in the stomach and reduces the amount of acid that the stomach secretes. People with the H. pylori bacterium who do not have this gene have less inflammation and are more able to fight off the infection. They also have higher levels of gastric acid, which promotes digestion and help cleanse the stomach of harmful substances.

Although stomach acid is often blamed for indigestion, El-Omar says that it is actually a good thing: "Gastric acid is the stomach's first line of defense."

People who have the "low acid" gene are less able to fight off H. pylori and other infections. The result is that inflammation can spread throughout the stomach and eventually damage the cells that produce stomach acid. This decreases the stomach's ability to defend itself against toxins that can cause cancer, El-Omar says.

El-Omar found that normally occurring variations in the gene explain whether a person will develop ulcers or cancer -- or nothing -- in response to an H. pylori infection.

"If you have a duodenal ulcer, it is your insurance policy against gastric cancer," El-Omar tells WebMD. "We wondered why that is. One clue was that when gastric acid secretion is inhibited for a long time in the presence of H. pylori, there can be a shift in the pattern of gastric inflammation from the ulcer type (which occurs in the lower part of the stomach) to the cancer-associated type (in the upper part). We suspected that genetic factors might partly explain the difference."

The researchers calculate that the "high risk" gene may be responsible for 38% of stomach cancers. Stomach cancer is the second most common form of cancer worldwide, and people who have H. pylori in their stomachs are three to six times more likely to develop it than those who don't. About half the world's population carries the bacterium.

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Neal J. Meropol, MD, tells WebMD that a test for the gene variation that El-Omar found would help doctors decide which patients are at high risk for gastric cancer. Those patients could then be singled out for especially careful follow-up. Meropol, who was not involved in the study, is director of the Gastrointestinal Cancer Program at the Fox Chase Cancer Center in Philadelphia.

"It is clear that there is an interaction between environmental factors and the host, or patient, in terms of risk for many types of cancer," Meropol says. "Why do some people smoke but never develop lung cancer? Why do some patients with H. pylori get ulcers while others develop gastric cancer? ...The future is that we are going to be [examining the genes of] both the tumor and the patient to determine the best approach to therapy."

Vital Information:

  • Researchers have found a genetic explanation for why people infected with H. pylori are at high risk for either stomach cancer or ulcers, but not both.
  • Some people have a gene that causes them to produce low levels of gastric acid, leaving the stomach less able to fight off toxins and the H. pylori infection, which can lead to cancer.
  • Others, who lack the gene, produce higher levels of gastric acid in the stomach, which kills off infection but may cause ulcer formation.
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