Gastric (stomach) cancer is the second most common type of cancer in the world. Most cancers of the stomach arise in the antrum, which is the lower third of the stomach, near the duodenum. There are different kinds of stomach cancers, depending on the type of cells from which the cancer arises. Cancers that form in the stomach’s secretory glands are called adenocarcinomas; these are the most common form, accounting for more than 90 percent of all stomach cancers. Adenocarcinoma of the stomach is strongly associated with H. pylori infection. Recent studies of patients with stomach cancer have revealed that over 90 percent of people who develop adenocarcinoma of the stomach have H. pylori infections. So, what is it about H. pylori that predispose certain people to develop cancer? A recent theory on the development of stomach cancer revolves around the interaction between the H. pylori organism itself and the infected person’s own immune response.
The role of H. pylori in the development of stomach cancer fits the multi-stage theory of carcinogenesis very well. There are two important factors in the formation of gastric cancer, and it is likely that they act in a cooperative manner to produce the cancerous changes. First, the host’s own immune system, which releases bacteria killing products as it battles infection, causes damage to the DNA of the stomach lining’s cells (initiation). Second, the bacterium itself and the products that it makes may directly injure or kill
the cells lining the stomach, leading to an increased turnover rate of cells in the tissue (promotion), a decreased rate of cell death, and a change in gene expression that leads to a shift away from normal stomach cell functioning.
The strain of H. pylori to which a person is exposed may influence the risk of developing gastric cancer. Strains of H. pylori that produce high levels of two proteins, vacuolating toxin A and the cytotoxin-associated gene, appear to cause greater tissue damage than those that produce lower levels, or that lack those genes completely. These proteins are directly toxic to cells lining the stomach, and signal strongly to the immune system that an invasion is underway. As a result of the bacterial presence, neutrophils and macrophages set up residence in the tissue to fight the bacteria assault.
Macrophages and neutrophils produce a number of substances that are destructive to neighboring cells, and that may in fact lead to mutations in the DNA of tissue cells. One of these substances is nitric oxide (NO), an antibacterial product that is made by neutrophils and dumped into the surrounding area to cleanse the region of invading microbes. NO, however, is a powerful oxidizing agent (similar to hydrogen peroxide); the activity of these strong oxidants causes small breaks in the DNA of the cells immediately surrounding the neutrophil. These breaks can lead to a loss of genes (such as tumor suppressors), a rearrangement of genes, or to other genetic mutations that change how the protein functions (including, for example, permanent activation of oncogenes, which promote cell growth, or inactivation of genes that stop cell growth). Indeed, a number of gastric cancers have been observed to cause a loss of the tumor suppressor function, an activation of oncogenes, and changes in many other genes that regulate the rate of cell growth and apoptosis. These changes in DNA and gene expression are also reflected in the re-organization of cells in the tissues.
Eventually, the dysplastic tissue may become cancerous, or malignant. Malignant cells may then gain the ability to move out of their immediate vicinity to more distant sites. They do this by entering the circulatory or lymph systems, by which they are carried to other organs, such as the liver or pancreas. This process is known as metastasis. There, the cells form metastatic colonies that hijack the function of the organ to which they have spread. So, for example, if the gastric adenocarcinoma metastasizes to the liver, cancer cells replace normal liver cells in the region of the liver where the cancer is growing.
That area then ceases to function like liver tissue, and begins to function like the cancer tissue that has replaced it. This is a very serious stage in the life cycle of the disease, a stage at which medical treatment becomes more difficult. As with most cancers, early intervention improves the outcome. Early diagnosis and medical treatment are very important in helping a person to recover from gastric cancer.
