Thursday, January 10, 2013

Background on Hereditary Gastric Cancer

** I received this background from the BC Cancer Agency in Canada. I thought I'd share it because it explains a lot of useful information on HDGC.

Worldwide, gastric (stomach) cancer is the second most common form of cancer. Although the total number of individuals diagnosed with gastric cancer have been decreasing over the years in North America and Western Europe, it is still relatively common in certain parts of Asia and Latin America.

The stomach is part of the digestive system and is located in the upper abdomen under the ribs. Gastric cancer can develop in any part of the stomach and may spread throughout the stomach and to other organs. Gastric cancer is treatable if it’s diagnosed in the early stages of the disease. The 5-year survival rate for gastric cancer is 90 percent when the cancer is detected in its earliest Stages. When the cancer has spread, the outlook is not as good for the patient. Unfortunately, most people do not receive a diagnosis until the cancer is more advanced. The reason for the lack of early diagnosis is that the cancer is difficult to detect in its early stages. Generally, there are no symptoms and the only evidence may be microscopic bleeding from the surface of the stomach. By the time symptoms do occur, the disease is often at a more advanced stage and no longer treatable. The diagnosis is sometimes made more difficult because the symptoms are very similar to those caused by ulcers.

The exact causes of gastric cancer are still largely unknown. Most cases of gastric cancer are sporadic in nature (that is, not inherited). Some of the risk factors in the sporadic cases include increasing age (generally people over 60 years), dietary factors, Helicobacter pylori infection, smoking, alcohol consumption, and a disorder of the blood called pernicious anemia. In about 1-3 % of all individuals who are diagnosed with gastric cancer and who have a strong family history of gastric cancer, the condition is caused by inherited mutations (changes) in genes that predispose individuals to gastric cancer.

There are 2 main types of gastric cancer - diffuse type and intestinal type. The intestinal type is more common than the diffuse type. The patients are usually older, patients are more likely to be male and it forms a typical visible tumor in the stomach. H pylorí plays an important factor in its development.

Diffuse type gastric cancer is somewhat more common in younger patients and it occurs in similar numbers in men as in women. It is not known what role Helicobacter pylori plays in the development of this type of cancer. Diffuse gastric cancer often presents with diffuse thickening of the stomach wall, rather than a visible mass (linitis plastica).

Inherited information is contained in structures called chromosomes that are found in every cell of our body. We have 46 chromosomes that occur in pairs; 23 from our mother and 23 from our father. Each chromosome is made up of hundreds to thousands of genes. Hence, the genes also come in pairs. Genes are packages of inherited information and act as instructions for making proteins (specific substances in our bodies) that help it to function properly. An alteration in this genetic information can cause a change in the instructions of the gene and interfere with normal protein function and hence proper body functions. These gene alterations are called mutations. There are certain genes that cause an increased chance to develop cancer when they have mutations. These genes are known as cancer susceptibility genes.

Most cancers occur as a result of sporadic mutations that occur in the body during a person’s life-time.  These mutations tend to occur as mistakes when the cells undergo division (a normal process) or in response to environmental factors. These mutations are not passed on to children. Hereditary Cancer occurs when a gene mutation is passed down from parent (through the egg or the sperm) to child. Since the mutation is present right from the beginning, it is found in every cell of the body. Cancer will develop only when both genes in a pair are mutated, Hereditary cancer tends to develop at a younger age since the individual is already born with one mutation and needs only to acquire one additional sporadic mutation in the other gene for cancer to occur.

There are believed to be several genes involved in hereditary gastric cancer. One of these, E-cadherin (or CDH1) is mutated in only one-third (33%) of the families that have hereditary diffuse gastric cancer. That means that other families with either the diffuse or intestinal type gastric cancer have mutations in other cancer genetic susceptibility genes.

E-cadherin is located on chromosome 16. Everybody has two chromosome 16’s and therefore two E-cadherin genes. E-cadherin is an important protein that helps to hold cells together. In cancer cells, when E-cadherin is either partly or completely missing, the cells detach themselves from each other and from the whole mass that holds everything together. If an individual inherits one E-cadherin gene with a mutation, damage to the remaining normal E-cadherin gene may be the event that starts off the stomach cancer. In individuals who inherit a mutated E-cadherin gene, the chance of developing stomach cancer depends on whether the person is male or female. In males, the chance of stomach cancer is 67% over the lifetime. In females, the lifetime chance of getting stomach cancer is 83%. Females with the mutation are also believed to have a 39% lifetime chance of having lobular (the part of the breast where milk is made) breast cancer. Therefore, not everyone who carries the mutation develops cancer but the risk is increased considerably over the general population risk (2000 times higher than the general population). When one parent carries a mutation in a cancer susceptibility gene such as E-cadherin, each one of his or her children has a 50% chance of inheriting that mutation. Males and females are both capable of passing the mutation down as well as inheriting the mutation.


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