Helicobacter pylori
(H pylori) is a bacteria that causes stomach ulcers, and is a known risk factor
for stomach cancer. Some studies have shown that infection with H pylori
increases the risk of pancreatic cancer. Millions of people are infected with H
pylori and most do not get these types of cancer, and so there must be other
factors at work.
What is
Helicobacter pylori?
Helicobacter pylori, or H. pylori, is a spiral-shaped
bacterium that grows in the mucus layer that coats the inside of the human
stomach.
To survive in the harsh, acidic environment of the
stomach, H. pylori secretes an enzyme called urease, which converts the
chemical urea to ammonia. The production of ammonia around H. pylori
neutralizes the acidity of the stomach, making it more hospitable for the
bacterium. In addition, the helical shape of H. pylori allows it to burrow into
the mucus layer, which is less acidic than the inside space, or lumen, of the
stomach. H. pylori can also attach to the cells that line the inner surface of
the stomach.
Although immune cells that normally recognize and attack
invading bacteria accumulate near sites of H. pylori infection, they are unable
to reach the stomach lining. In addition, H. pylori has developed ways of
interfering with local immune responses, making them ineffective in eliminating
this bacterium.
H. pylori has coexisted with humans for many thousands of
years, and infection with this bacterium is common. The Centers for Disease
Control and Prevention (CDC) estimates that approximately two-thirds of the
world’s population harbors the bacterium, with infection rates much higher in
developing countries than in developed nations.
Although H. pylori infection does not cause illness in
most infected people, it is a major risk factor for peptic ulcer disease and is
responsible for the majority of ulcers of the stomach and upper small
intestine.
In 1994, the International Agency for Research on Cancer
classified H. pylori as a carcinogen, or cancer-causing agent, in humans,
despite conflicting results at the time. Since then, it has been increasingly
accepted that colonization of the stomach with H. pylori is an important cause
of gastric cancer and of gastric mucosa-associated lymphoid tissue (MALT)
lymphoma.
H. pylori is thought to spread through contaminated food
and water and through direct mouth-to-mouth contact. In most populations, the
bacterium is first acquired during childhood. Infection is more likely in
children living in poverty, in crowded conditions, and in areas with poor
sanitation.
Research
While most people with H. pylori will not become ill,
doctors have determined that anywhere from two to 20 percent of those infected
will develop ulcers. Not only that, some studies show a possible link to
stomach cancer and pancreatic cancer.
From 1984 to 1995, researchers followed 29,133 male
smokers age 50 to 69 who lived in Finland and were participating in a trial
called the Alpha-Tocopherol, Beta-Carotene (ATBC) Cancer Prevention Study.
Given that smoking increases the risk of pancreatic cancer, a higher number of
participants developed cancer than might be found in other studies.
Among those who got pancreatic cancer, those infected
with H. pylori seemed to be at higher risk. In fact, those with a strain of H.
pylori called cytotoxin-associated gene A positive (CagA+) had an approximately
two-fold increase compared with people not infected with H. pylori.
In a more recent study, researchers investigated the
effect of H. pylori infection on pancreatic cells in the laboratory. Certain
growth factors that may increase risk of pancreatic cells becoming malignant
increased when the cells were cultured with H. pylori. Another study published
in early 2010 found that H. pylori in people with non-O blood types was
associated with a three-fold increase in the risk of pancreatic cancer.
"My question would be where [H. pylori fits] in the
risk for pancreatic cancer," says Dr. Lewin. "For example, [does it
work] in combination with smoking or other risk factors so that it makes a
difference, or is it an independent variable that is a significant cause? Or
does it simply amplify the risk of other factors? Does it make any difference
at all in real people’s bodies — rather than the test tube?"
Other studies have found no connection. A recent study of
patients in the Kaiser Permanente Medical Care Program found no association
between H. pylori or the CagA+ strain and pancreatic cancer. Another comparison
conducted in Sweden had similar results, also finding no link between H. pylori
infection and pancreatic cancer within the group at large. Interestingly, this
study did find possible increased odds of pancreatic cancer in people who had
never smoked, as well as in people with low alcohol consumption. However, given
the small number of such cases in the study, more research is needed before
drawing any definitive conclusions.
Clearly, results are contradictory and more research is
needed. With an estimated 42,470 new cases of pancreatic cancer diagnosed last
year and about 35,240 deaths from the disease, additional information about
risk factors and early detection methods is crucial.
Blood Types
A research team from the Yale Cancer Center Prevention
and Control Research Program examined the association between H. pylori,
different blood groups, and risk of pancreatic cancer. Having reviewed the
scientific literature, which includes studies showing an increased risk of
pancreatic cancer for blood group A, blood group B, and blood group AB
individuals when compared with blood group O individuals, the researchers
hypothesized that the increased risk of pancreatic cancer from an H. pylori
infection may be correlated with blood type. To test their theory, they
conducted a population-based study of 373 case patients and 690 control
subjects. The study was funded by the National Cancer Institute and approved by
the State of Connecticut Department of Public Health.
"This study demonstrates an association between
pancreatic cancer and H pylori colonization, particularly for individuals with
non-O blood types," wrote the authors. "However, presence of the CagA
virulence protein may temper the effect of H pylori on pancreatic cancer
risk."
Scientists divide H. pylori strains into CagA
(cytotoxin-associated gene A) positive or negative strains; the majority —
upwards of 90 percent — of East Asian H. pylori isolates are positive while
less, around 60 percent, of isolates in Western countries are found to be
positive. In the study, then, the increased risk of pancreatic cancer was only
associated with H. pylori when it was determined to be CagA-negative.
Along with increased investigation of H. pylori,
scientists have also begun to further examine other bacteria, such as
Porphyromonas gingivalis, to better understand how they might increase risk for
the disease.
What are the
symptoms of H. pylori infections?
Most individuals infected with H. pylori have few or no
symptoms. They may experience a few episodes of gastritis (minor belching,
bloating, nausea, vomiting, abdominal discomfort), but little or nothing else.
Often, these symptoms simply cease. However, those individuals who have a more
serious infection exhibit symptoms of stomach and duodenal ulcers or gastritis,
which include the following:
* Abdominal pain and/or discomfort that usually does not
wax and wane
* Nausea and vomiting sometimes with blood or
coffee-ground like vomitus
* Dark or tar-like stools (black color of feces due to
bleeding ulcers)
* Fatigue
* Low red blood cell count due to bleeding
* Full feeling after a small amount of food; decreased
appetite that is more constant
Other symptoms may include diarrhea, heartburn, and bad
breath (halitosis). Symptoms of black, tarry stools and fatigue should cause a
person to seek medical help or go to an emergency department to be evaluated
for intestinal bleeding.
Why infection is
linked to pancreatic cancer?
Several theories aim to explain why these infections may
be contributing to the progression of pancreatic cancer. One is that the
infections cause body wide inflammation, which is known to play a role in
pancreatic cancer.
A second possible mechanism is that these bacterial
infections lead to changes in the immune system. When the immune system is
weakened or altered by infection, it does not work as well to defend the body
against cancer.
What's more, risk factors for pancreatic cancer, such as
smoking, obesity and diabetes, may further suppress immune response, opening
the door to opportunistic infections.
Other theory is that these bacterial infections may
directly activate pancreatic tumor signaling pathways, such as those that
promote the growth of new blood cells that feed a tumor.
Another
possibility is that infections indirectly activate pancreatic cancer pathways
that trigger an immune response in the environment surrounding the cancer, but
not in the tumor itself.
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