Carolyn Vachani, MSN, RN, AOCN
The Abramson Cancer Center of the University of Pennsylvania
Last Modified: December 12, 2007
Colorectal cancer accounts for 14% of all cancer deaths in the United States. There were an estimated 135,400 new cases and 56,700 deaths in the United States in 2001. Approximately 10 to 15% of these cancers may be caused by genetic abnormalities that run in families. There are two major types of known hereditary disorders, familial adenomatous polyposis (also known as FAP) and hereditary nonpolyposis colorectal cancer (also known as HNPCC). In this article, we will address FAP.
FAP accounts for only one percent of new colorectal cancer cases each year, affecting about 1 in 9,000 people. About 15% of people with FAP develop polyps by the age of 10, and 90% develop them by the age of 30. Affected patients can develop hundreds to thousands of adenomatous polyps, and have a 100% chance of developing colorectal cancer by age 40 if they do not have their colon removed. Adenomatous polyps are considered to be "pre-cancerous" lesions, some of which will eventually progress to cancer. Therefore, the more polyps an individual has, the greater his or her chance of developing cancer. The average age of colorectal cancer diagnosis in FAP is 35 years, as compared to 64 years in the general population.
Colon with multiple adenomas, Photo courtesy of Mt. Sinai Hospital in Toronto, Canada.
Several other cancers have been associated with FAP, including periampullary and thyroid cancer. Periampullary (cancer that is found in the area where the bile duct and pancreas empty into the small bowel) is the second most common cancer in FAP, and accounts for 1 in 5 deaths of these patients. In addition, several other non-cancerous manifestations have been seen in FAP. Young FAP patients may develop cysts in the skin on the face, scalp, arms, and legs, often years before they develop colon polyps. Congenital hypertrophy of the retinal pigment epithelium (also called CHRPE) is an abnormality found in the retina of the eye that looks like a freckle and causes no symptoms for the patient. While CHRPE can be seen in one eye of individuals without FAP, it is often present in both eyes in an FAP patient. About 70% of FAP patients have dental abnormalities, including extra or missing teeth, fused roots, or non-cancerous tumors of the jaw bone (osteomas). Although these manifestations are not harmful to the patient, they may be the first sign of FAP and prompt a patient to undergo testing for FAP. Ten percent of FAP patients will develop desmoid tumors, which are non-cancerous, slow-growing tumors, which occur in the abdominal area. Despite the fact that these tumors are not cancerous, they can cause significant damage by surrounding, compressing, and eroding nearby structures, and may need to be removed surgically. In the past, the term "Gardner's Syndrome" was been used to describe a subset of FAP patients that have CHRPE, dental abnormalities or desmoid tumors, and was thought to be genetically different. It is now known that these features are seen in many FAP patients and these cases are not genetically different.
Congenital hypertrophy of the retinal pigment epithelium, Photo courtesy of Mt. Sinai Hospital in Toronto, Canada.
In 1991, the gene responsible for FAP was discovered and was named the Adenomatous Polyposis Coli, or APC gene. Scientists have discovered over 300 different mutations in the APC gene which can cause FAP. The location of the mutation on the gene often correlates with the number of polyps, age of onset, and other manifestations. FAP is an autosomal dominant inherited disorder, meaning that a child of an affected parent has a 50% chance of inheriting the mutation. Approximately 30% of FAP cases are "de novo mutations", meaning they have no prior family history of the mutation.
The diagnosis of FAP is made by discovering >100 adenomatous polyps or through genetic testing in a known FAP family. Once a person is diagnosed, an analysis of the family should be done to determine the likelihood that other relatives have the condition. Genetic testing can identify the specific abnormality in the affected individual, and then look for this defect in other family members. It is recommended that children of FAP patients undergo genetic testing or endoscopic screening by age 10. If genetic tests are positive in these children, endoscopic screening should continue every 1 to 2 years. If genetic testing is negative, these people can be spared the intensive screening.
Genetic testing is something that should not be taken lightly. One must consider the affect of the test results on themselves and other family members. Concerns may include the implication of a positive or negative test, passing the gene on to children, and discrimination in employment and insurance matters. A genetic counselor should meet with anyone wishing to undergo testing, both before testing and after the results are known. These professionals are trained to help patients understand the risks and benefits of testing and what to do with the results.
There is no medication to prevent the development of colon polyps in FAP, but non-steroidal anti-inflammatory drugs (NSAIDS such as sulindac and indomethacin) have been shown to shrink polyps in these patients. Clinical trials are currently examining ways to prevent polyp growth in these patients. Until better medical therapies are developed, these patients require surgical removal of the colon (colectomy) to prevent the development of colon cancer. This surgery is often performed between the ages of 17 and 20 in asymptomatic members of FAP families. There are several surgical options for these patients, but the goal is to remove all colorectal tissue at risk for developing polyps and maintain normal bowel evacuation through the anus.
FAP is one of the most well understood inherited cancer syndromes. This knowledge has led to the availability of genetic testing for at risk individuals, improved screening and surgical management, and clinical trials for the prevention of polyp formation. Continued research into FAP will lead to better treatments for these families, and may have implications for all colon cancer patients.
To learn more about surgical options for FAP, visit the Mt. Sinai Hospital website from Toronto, Canada.
Learn more about the ileo-anal anastomosis procedure and support.
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Learn more about cancer family registries.
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