Gene May Explain Why Some Have Higher Stomach Cancer Risk
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
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
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
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.
"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.
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
"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."