Medical College of Wisconsin researchers recently reported on
a study linking Helicobacter pylori to precancerous lesions
of the stomach. By infecting specially bred mice with H pylori
and showing the resulting precancerous changes in their stomachs,
the researchers have uncovered an important clue to the origins
of stomach cancer. Their results are the closest evidence to date
showing that H pylori causes stomach cancer in any animal
Until about 10 years ago doctors thought the stomach was a sterile
environment, explained Bruce Dunn, md, associate professor of
pathology at the Medical College. Gastric juices are so potent
that they assumed no bacteria could live in them. Then came the
discovery that H pylori could, indeed, survive in the stomach;
it causes gastritis and peptic ulcers. A percentage of people
with gastritis go on to develop stomach cancer.
The natural follow-up question was, does H pylori play
a role in stomach cancer? Based on epidemiologic studies, the
answer seemed to be "yes." A correlation has been established
between some strains of H pylori infection and development
of stomach cancer, but this correlation needs to be demonstrated
in 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 Medical
Beyond the Tumor-Suppressor Gene
Scientists know that for most cancers to develop, there must be
a mutation in the tumor-suppressor gene, p53. They have bred a
strain of laboratory mice without this gene, who then go on to
develop lymphatic cancer. But the mice don't develop stomach cancer,
which suggests that, in addition to the absence of the tumor-suppressor
gene, something else must be present in order for this cancer
Drs. Dunn and Phadnis infected p53-deficient mice with H pylori
to see if they would develop stomach cancer. The answer, so far:
"The mice don't develop cancer, but they do develop dysplasia
which is a significant precancer stage," said Dr. Dunn. Drs.
Dunn and Phadnis think the reason the p53-deficient mice don't
get full-blown cancer is because of their short life span. Stomach
cancer in humans seems to take years, or even decades, to develop.
The researchers are now studying the combined effects of H
pylori and low levels of known carcinogens to see whether
there is a synergistic effect that can be observed during the
life span of the mice.
A second area of their research is an attempt to discover how
the H pylori bacteria manage to stay alive in the hostile
stomach environment. The theory is that they "wrap"
themselves in a shield of ammonia made by breaking down urea present
in the gastrointestinal tract. The Wisconsin investigators hope
to prevent the enzyme urease (which breaks down the urea) from
doing its job. That could lead to a vaccine to prevent the consequences
of infection with H pylori, such as peptic ulcer and gastric
Dr. Dunn presented the research at the 14th annual Media Seminar
on Cancer on April 15, 1996, at the Medical College of Wisconsin.