Tuesday, November 25, 2014

Helicobacter pylori infection – risk factor for pancreatic cancer

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. 


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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