Medical College of Wisconsin Researchers Study Role of H pylori in Stomach Cancer

Medical College of Wisconsin researchers recently reported ona study linking Helicobacter pylori to precancerous lesionsof the stomach. By infecting specially bred mice with H pyloriand showing the resulting precancerous changes in their stomachs,the researchers have uncovered an important clue to the originsof stomach cancer. Their results are the closest evidence to dateshowing that H pylori causes stomach cancer in any animalmodel.

Until about 10 years ago doctors thought the stomach was a sterileenvironment, explained Bruce Dunn, md, associate professor ofpathology at the Medical College. Gastric juices are so potentthat they assumed no bacteria could live in them. Then came thediscovery that H pylori could, indeed, survive in the stomach;it causes gastritis and peptic ulcers. A percentage of peoplewith gastritis go on to develop stomach cancer.

The natural follow-up question was, does H pylori playa role in stomach cancer? Based on epidemiologic studies, theanswer seemed to be "yes." A correlation has been establishedbetween some strains of H pylori infection and developmentof stomach cancer, but this correlation needs to be demonstratedin a laboratory.

That's what Dr. Dunn and his colleague, Suhas H. Phadnis, phd,assistant professor of pathology, set out to do at the VA MedicalCenter.

Beyond the Tumor-Suppressor Gene

Scientists know that for most cancers to develop, there must bea mutation in the tumor-suppressor gene, p53. They have bred astrain of laboratory mice without this gene, who then go on todevelop lymphatic cancer. But the mice don't develop stomach cancer,which suggests that, in addition to the absence of the tumor-suppressorgene, something else must be present in order for this cancerto develop.

Drs. Dunn and Phadnis infected p53-deficient mice with H pylorito see if they would develop stomach cancer. The answer, so far:"The mice don't develop cancer, but they do develop dysplasiawhich is a significant precancer stage," said Dr. Dunn. Drs.Dunn and Phadnis think the reason the p53-deficient mice don'tget full-blown cancer is because of their short life span. Stomachcancer in humans seems to take years, or even decades, to develop.The researchers are now studying the combined effects of Hpylori and low levels of known carcinogens to see whetherthere is a synergistic effect that can be observed during thelife span of the mice.

A second area of their research is an attempt to discover howthe H pylori bacteria manage to stay alive in the hostilestomach environment. The theory is that they "wrap"themselves in a shield of ammonia made by breaking down urea presentin the gastrointestinal tract. The Wisconsin investigators hopeto prevent the enzyme urease (which breaks down the urea) fromdoing its job. That could lead to a vaccine to prevent the consequencesof infection with H pylori, such as peptic ulcer and gastriccancer.

Dr. Dunn presented the research at the 14th annual Media Seminaron Cancer on April 15, 1996, at the Medical College of Wisconsin.