About Gastric Cancer
Cause
For the vast majority of patients, stomach cancer is caused by random genetic events. That is "doctor-speak" for bad luck. Essentially, a mutation occurs in the DNA of a stomach cell that lines the inside of the stomach. This mutation is not caught by the cells repair machinery and after many replications and more mutations, eventually, the first cancer cell develops, which then leads to the cancer itself. This cancer cell carries with it the basic properties of cancer - that of continuously growing and producing more cancer cells and avoiding programmed cell death that was discussed earlier.
There are associations linked to the development of stomach cancer as well. For example, about 10-15% of all stomach cancers are inherited. There is also an association between stomach cancer and a bacterial infection of the stomach called Helicobacter pylori. H. Pylori infection causes inflammation and the stomach cells are damaged by cells of the immune system. It is not known exactly why this condition progresses to cancer, but may be related to the irritation caused by chronic inflammation.
Obesity, chronic heartburn, and tobacco and alcohol use are other characteristics associated with the development of stomach cancer. It is important to realize that not all patients with these characteristics will indeed develop the disease. Eating fruits and vegetables reduce the risk of developing stomach cancer.
It is important to realize that a stomach ulcer is not, by itself, associated with a high risk of stomach cancer. However, it may be an indicator that other risk factors for stomach cancer exist, such as infection with H. pylori or reflux disease, as these are also risk factors for stomach ulcers. Importantly, not all patients, and in fact, the majority of patients with gastric ulcers do not go on to develop stomach cancer.
Risk Factors
Helicobacter pylori or H. pylori: a bacterium that infects millions of people worldwide and is a major cause of stomach cancer. Long-term infection of the stomach with H. pylori may lead to chronic inflammation and damage to the inner layer of the stomach. This chronic inflammation may result in precancerous changes to the lining of the stomach. Patients with adenocarcinoma of the stomach have a higher rate of infection than those without cancer. Some strains of H. pylori are more commonly associated with the development of stomach cancer than other strains. H. pylori infection is also associated with some types of lymphoma of the stomach (e.g. MALT lymphoma). The exact mechanism by which infection with H. pylori leads to the development of stomach cancer is not well understood. Indeed, the vast majority of people who are infected with H. pylori never develop cancer of the stomach.
Dietary causes: People who eat diets containing large amounts of smoked foods, salted fish and meat, and pickled vegetables have an increased risk of getting stomach cancer. Nitrates and nitrites are substances commonly found in cured meats, some drinking water, and certain vegetables. These nitrates and nitrites can be converted by H. pylori into compounds that have been found to cause stomach cancer in animals. Eating whole grain products and fresh fruits and vegetables rich in vitamins A and C appear to lower the risk of stomach cancer.
Tobacco and alcohol abuse: Smoking increases stomach cancer risk, particularly for cancers of the proximal stomach (the upper portion of the stomach closest to the esophagus). The rate of stomach cancer is approximately doubled in smokers. Some studies have linked alcohol use to stomach cancer, but this is not certain.
Obesity: Obesity is a major cause of many cancers and especially cancers of the cardia (part nearest the esophagus) of the stomach. Obesity is related to increased reflux and irritation of the lining of the stomach, particularly in the cardia or lower esophagus.
Previous stomach surgery: Stomach cancers are more likely to develop in those that have had part of their stomach removed to treat non-cancerous conditions like ulcers. This may be due to the presence of more nitrite-producing bacteria. Acid production goes down after ulcer surgery and there may be reflux (backup) of bile from the small intestine into the stomach. The risk continues to increase for as long as 15 to 20 years following surgery and for those patients who underwent a Billroth II operation.
Pernicious anemia: Pernicious anemia occurs as a result of a vitamin B12 deficiency. There are certain cells in the lining of the stomach that normally produce a protein necessary for absorbing vitamin B12 from foods. If enough of this substance (called intrinsic factor) is not present, a vitamin B12 deficiency results, leading to anemia (a problem in producing enough red blood cells). In addition to anemia, there is an increased risk of stomach cancer for patients with this disease. Because the risk for developing stomach cancer from a vitamin B12 deficiency seems to be very small, screening these patients for stomach cancer is not recommended.
Menetrier disease: This is also known as hypertrophic gastropathy and is a condition of the large folds in the stomach. It is associated with changes in the stomach lining and low acid production. Because this disease is very rare, the exact risk of stomach cancer is not known.
Gender: Stomach cancer is more than twice as common in men as it is in women.
Ethnicity: Stomach cancer is more common in Hispanics and African Americans than in non-Hispanic whites. It is most common in Asian/Pacific Islanders.
Aging: There is an increase in stomach cancer after the age of 50. Most people diagnosed with stomach cancer are in their late 60s, 70s, and 80s.
Type A blood: Blood type groups refer to certain antigens that are normally present on red blood cells and some other types of cells. Antigens are chemicals that are recognized by the immune system. These groups are important in matching blood for transfusions. For reasons unknown, people with type A blood have a higher risk of developing stomach cancer.
Familial cancer syndromes: Hereditary nonpolyposis colorectal cancer (also known as HNPCC or Lynch syndrome) and familial adenomatous polyposis (also known as FAP) are inherited genetic disorders. People that are affected with these inherited genetic disorders and mutations have a greatly increased risk of developing colorectal cancer and a slightly increased risk of developing stomach cancer. People who carry mutations of the inherited breast cancer genes, BRCA1 and BRCA2, may also have a higher rate of stomach cancer. Recently, Diffuse Hereditary Gastric Cancer has been discovered as a new familial cancer syndrome for the development of diffuse stomach cancer. In this syndrome, patients from the same family who develop stomach cancer develop the diffuse type of stomach cancer, more often at an early age (age less than 50 years). The gene responsible for diffuse hereditary stomach cancer is CDH1, which is the gene for a cell surface protein called E-cadherin. People with several first-degree relatives who have had stomach cancer are more likely to develop this disease.
Stomach polyps: Polyps are non-cancerous growths on the lining of the stomach that can turn into cancer. Most types of polyps (such as hyperplastic polyps or inflammatory polyps) do not appear to increase a person's risk of stomach cancer. Adenomatous-type polyps (adenomas) can sometimes develop into cancer.
Geography: Stomach cancer is most common in Japan, China, Southern and Eastern Europe, and South and Central America. This disease is least common in Northern and Western Africa, South Central Asia, and North America. The cause for this geographic variation is not clear. The incidence of diffuse stomach cancer (Lauren's classification) is constant across the globe, at a rate of about 1-2/ 100,000 people. Unlike diffuse stomach cancer, the rate of intestinal-type stomach cancer varies across the globe, and is most prevalent in the areas with the highest rates of stomach cancer. For example, in Japan, where the rate of stomach cancer is one of the highest worldwide, the rate of intestinal stomach cancer is also amongst the highest in the world, whereas the rate of diffuse stomach cancer in Japan is the same as everywhere else in the world.
Epstein-Barr virus: This virus causes infectious mononucleosis. Almost all adults have been infected with this virus at some time in their lives, usually as children or adolescents. It has been linked to some forms of lymphoma. Epstein-Barr virus has also been found in the stomach cancers of about 5-10% of people with this disease. These people tend to have a slower growing, less aggressive cancer with a lower tendency to spread. It is unclear what role the virus plays in the development of stomach cancer.
Statistics
Stomach cancer is one of the most common diseases worldwide. About 975,000 new cases of stomach cancer were diagnosed worldwide in the year 2000. It is the 3rd most prevalent disease worldwide, and is responsible for about 734,000 deaths in the year 2000. In the United States, there will be about 21,260 new cases of stomach cancer diagnosed in 2007, and about 11,210 people (6,610 men and 4,600 women) will die of this disease. Two thirds of the people who have stomach cancer are 65 years or older. The risk of a person getting stomach cancer in their lifetime is about 1 in 100.
Stomach cancer is more common worldwide, particularly in less developed countries. It is the second-leading cause of cancer-related deaths in the world. Stomach cancer used to be a leading cause of cancer death in the United States, but now it is much less common. The reasons for this decrease in the incidence of stomach cancer are not completely known, but they may be linked to use of refrigeration for food storage and less use of salted and smoked foods. Some doctors believe the major reason that stomach cancer has decreased in incidence is because of the frequent use of antibiotics to treat infections in children. Antibiotics can kill the bacteria called Helicobacter pylori or H pylori, which may be a major cause of stomach cancer.
Warning Signs
Most cases of early stomach cancer do not present with clear symptoms. As the cancer grows and spreads, the most common symptoms are discomfort in the stomach area, feeling full or bloated after a small meal, blood in the stool, unexplained weight loss, loss of appetite, heartburn or indigestion, and nausea and vomiting. Most patients have symptoms for 3-9 months before being diagnosed with the disease.
In more advanced cases of stomach cancer, symptoms may include jaundice (yellowing of the eyes and skin), ascites (fluid build-up in the abdominal area), and having trouble swallowing. Some of these symptoms can occur with non-cancerous conditions, such as a stomach virus, or with other types of cancer. Often these symptoms are not due to cancer, but it is always best to check with your health care provider.
