Familial adenomatous polyposis

An individual who has a mutation in the APC gene has a 50% chance to pass the mutation on to each of their children. The siblings of an individual who has a mutation have a 50% chance to inherit the mutation. Most often, the mother or father of an individual who carries a mutation also carries the mutation, but this is not always true with FAP. Sometimes a mutation in the APC gene happens for the first time in an individual and was not inherited from their mother or father.

For MUTYH-associated polyposis, if an individual has two mutations in the MUTYH gene, each of their siblings has a 25% chance of also having two mutations. It is recommended that the partner of an individual who has MUTYH-associated polyposis receives genetic testing of the MUTYH gene to determine the risk for their future children to have MUTYH-associated polyposis.

Since screening for colon polyps begins at a young age with this condition, a discussion with a genetics provider and your child’s doctor is recommended to determine the best time to perform genetic testing. Genetic testing for a hereditary cancer condition is an individual’s choice, and is an option available, but not mandatory, for other family members.

To find other people with familial adenomatous polyposis visit:

If you have too many polyps found during a colonoscopy and they all cannot be removed during the colonoscopy, this may be when removal of the colon would be recommended. This decision will be made with your gastroenterologist and a surgical team.

A gastroenterologist (gastrointestinal specialist) can help manage the colonoscopy and the upper endoscopy screening necessary for individuals with familial adenomatous polyposis.

An endocrinologist (doctor who specializes in diseases of endocrine, or hormone-producing, glands) can manage the thyroid screening recommended for familial adenomatous polyposis

Approximately 1% of all colon cancers are due to familial adenomatous polyposis.

FAP is the abbreviation for familial adenomatous polyposis. The abbreviation for attenuated familial adenomatous polyposis is AFAP. The abbreviation for MUTYH-associated polyposis is MAP.

You should discuss your specific prep recommendations with your doctor who will give you more specific and detailed instructions. The goal of the prep is to get your colon as clean as possible before the examination. In general, the prep consists of: drinking clear liquids only 24 hours before the exam, not eating solid foods, and drinking a large amount of a special cleansing solution and/or special oral laxatives recommended by your doctor.

The average age that someone with attenuated familial adenomatous polyposis is usually diagnosed with colon cancer is 50-55 years old.

The average age that someone with familial adenomatous polyposis is usually diagnosed with colon cancer is 39 years old.

Familial adenomatous polyposis (FAP) is an inherited condition that runs in the family and causes an increased risk for people who have it to grow many (over one hundred) polyps in their colon. Polyps are abnormal growths of tissue that can turn into cancer if left untreated. The type of polyps found in FAP are called adenomatous polyps. There is also a predisposition for developing other cancers including: small intestinal cancer, pancreatic cancer, thyroid cancer, and hepatoblastoma (tumor of the liver) in children. Having a mutation in the APC genes does not guarantee someone will develop cancer. However, if left untreated, up to 93% of individuals with FAP will develop colon cancer by age 50.

In addition to the standard form of FAP, there are two milder forms of this condition: attenuated familial adenomatous polyposis (AFAP) and MUTYH-associated polyposis (MAP). These forms of FAP are associated with less polyps, but still carry a higher risk of colon cancer than the average person.

Colon polyps often do not cause any symptoms. But, some people with colon polyps may experience rectal bleeding, change in color of the stool (blood may make the stool appear black or it may have red streaks), change in bowel habits including constipation or diarrhea, pain, nausea, vomiting, or iron deficiency.

Symptoms of colon cancer may include: a change in bowel habits including constipation, diarrhea, or narrowing of the stool, which lasts for more than a few days, feeling that you need to have a bowel movement but the feeling is not relieved by doing so, blood in the stool, rectal bleeding, cramping or abdominal pain, weakness, fatigue, and unintended weight loss.

Familial adenomatous polyposis should be considered whenever an individual has a personal history of 20 or more adenoma polyps.

FAP should also be considered when there is a personal or family history of:

The MUTYH gene provides instructions for an enzyme (type of protein) called MYH-glycosylase, which is involved in DNA repair. This enzyme helps to correct mistakes that are made when DNA copies itself before the cell divides, and it helps fix mistakes so that mutations do not accumulate in the DNA and lead to the development of a tumor. If there is a change in the MUTYH gene, cells are unable to correct mistakes in the DNA, so the body cannot protect itself from developing tumors as well as it normally should. Because of this, MUTYH is a gene that when changed can cause familial adenomatous polyposis, an increased risk for colon cancer and multiple polyps in the colon that runs in the family.

The APC gene provides instructions for making the APC protein. The APC protein plays an important role in multiple different cell functions. The APC protein normally acts as a tumor suppressor, which means that it keeps cells from growing and dividing too fast or in an uncontrolled way. The APC protein also helps control how often a cell divides, how it attaches to other cells within a tissue, and helps to make sure the correct number of chromosomes (the structures that contain the genes) are present in a cell. APC also works together with other proteins, including a protein called beta-catenin. Beta-catenin helps to promote cell division and growth and helps control activity of certain genes. If there is a mutation, or change, in the APC gene the protein cannot stop cellular overgrowth and this can lead to the formation of polyps in the colon, which can become cancerous. APC is one gene that when changed can cause familial adenomatous polyposis, an increased risk for colon cancer and multiple polyps in the colon that runs in the family.

During a laparoscopic colectomy, the surgeon enters the abdomen by placing a narrow-like instrument into the abdomen through a small incision. Carbon dioxide is pumped into the abdomen through the narrow-like tube to create more space within the abdomen. A tiny telescope connected to a video camera (laparoscope) is inserted to view the colon. The parts of the colon that need to be removed are then freed from the attachments to other organs and the abdominal wall. The blood vessels that provide blood to the colon are sealed to help prevent bleeding. The colon is removed through the small incisions made in the abdomen. The two remaining ends of the colon, or the rectum and the small intestine, are then reconnected.

The surgery for the open surgery is essentially the same, but the surgeon works with more traditional handheld instrument through a larger, single incision.

The main gene associated with FAP is APC. Harmful changes (mutations) in the APC gene cause an increased risk for multiple polyps in the colon and/or colon cancer and these gene mutations run in families. Most of the time if an individual has standard FAP they will have an identifiable mutation in the APC gene. However, if someone has attenuated FAP they will an identifiable mutation, or change, in this gene only 30% of the time. Another gene that runs in families, MUTYH, can also cause multiple colon polyps and/or colon cancer, but does not tend to be associated with other tumors outside of the colon. Still other genes that may cause FAP have yet to be identified.

A variant of uncertain significance (VUS), means that there is a change in the DNA sequence of a gene, but it is not yet known whether this variant impacts the ability of the protein to do its job or is associated with risk for disease.

A colectomy is the removal of part of the colon or the entire colon. The portion of the colon removed depends on the nature and number of polyps detected. The removal of the colon can be performed in two ways: open surgery or laparoscopic surgery. For the open surgery, there would be a long incision down the center of the abdomen where the colon would be removed. For the laparoscopic surgery, the surgeon uses several very small incisions and specialized instruments to remove the colon. In general, the laparoscopic surgery has a shorter recovery period in the hospital than the open surgery. The type of surgery recommended may depend on which hospital you are at and the doctors that you are working with.

The main symptom of familial adenomatous polyposis is development of colon polyps. However, colon polyps often do not cause any symptoms and are only found on a test that helps doctors see into the colon called colonoscopy. Some people with colon polyps may experience rectal bleeding, change in color of the stool (blood may make the stool appear black or it may have red streaks), or change in bowel habits including constipation or diarrhea, pain, nausea, vomiting, or iron deficiency.

Symptoms of colon cancer may include: a change in bowel habits including constipation, diarrhea, or narrowing of the stool, which lasts for more than a few days, feeling that you need to have a bowel movement but the feeling is not relieved by doing so, blood in the stool, rectal bleeding, cramping or abdominal pain, weakness, fatigue, and unintended weight loss.

The types of cancer that are suggestive of familial adenomatous polyposis include: colon cancer, ten to hundreds to thousands of adenomatous polyps, small intestinal polyps or cancer, stomach polyps (fundic gland polyps), pancreatic cancer, thyroid cancer, brain tumor (medulloblastomas are most common), and hepatoblastoma (tumor of the liver) in children. There are other, non-cancerous, findings that are also suggestive of familial adenomatous polyposis which include: osteoma (bony growth, usually on the head), epidermoid or sebaceous cysts (small lumps under the surface of the skin or of the oil glands of the skin), desmoid (abnormal growth of tissue typically arising in abdomen), CHRPE (a spot on the retina of the eye), cysts on the jawline, and extra teeth or baby teeth that never fell out.

To establish the extent of disease and needs in an individual diagnosed with familial adenomatous polyposis, the following evaluations are recommended:

Some individuals may develop cancer earlier or later than others within their family or between different families, which is known as a variable age of onset. Individuals who have a mutation in the APC gene may never develop the cancerous (or non-cancerous) findings associated with familial adenomatous polyposis, which is known as incomplete penetrance, while other individuals may develop some of these findings and their family members may develop different findings associated with familial adenomatous polyposis, and this is known as variable expression.

Having more than 20 adenomatous polyps is considered unusual in the general population and is suggestive of familial adenomatous polyposis.

CHRPE (congenital hypertrophy or hyperplasia of the retinal pigment epithelium) are benign (non-cancerous) lesions on the retina that are highly suggestive of FAP. Singular lesions would not lead to the diagnosis of FAP but the presence of 4 or more lesions is highly specific for the diagnosis of FAP. CHRPE has been reported in up to 90% of patients with FAP. However, genetic testing is still the standard of care for diagnosing FAP.

There is not newborn testing for familial adenomatous polyposis at this time.

There are different options for genetic testing. A meeting with a genetics health provider for genetic counseling can help determine which option of genetic testing makes the most sense for you based on your personal or family history. An individual may be only tested for the APC gene. An individual may be tested for the APC gene along with multiple other genes that can also cause an increased risk for colon polyps, including the MUTYH gene which causes MUTYH-associated polyposis. Testing multiple genes at once is called a cancer gene panel. A genetic counselor focused on cancer in your area can be found at www.nsgc.org website.

There are over 20 clinical trials recruiting participants with familial adenomatous polyposis. There are 20-30 other clinical trials that have already been completed and for some of the trials the results are available. The clinical trials range from genetic testing, medications, screening for desmoid tumors, and new surgical treatments. The easiest place to look for more research on familial adenomatous polyposis is to search for studies on the website: www.clinicaltrials.gov.

An FDA-approved treatment exists for familial adenomatous polyposis (FAP) in the United States. The FDA has approved celecoxib (Celebrex; G. D. Searle & Co, Chicago), an anti-inflamatory cyclooxygenase 2 inhibitor, as the first chemopreventive drug treatment for familial adenomatous polyposis (FAP). The new indication is for reduction in the number of adenomatous colorectal polyps in FAP, as an adjunct to endoscopy and surgery. In the pivotal studies, the mean reduction in the number of polyps was 28% for 400 mg of celecoxib twice daily, 12% for 100 mg twice daily, and 5% for placebo.

There is also evidence that taking a combination of 2 medications, sulindac (Clinoril) and erlotinib (Tarceva), decreased the number of colorectal and duodenal polyps. While this is promising, this treatment is not currently standard-of-care as further research is needed to determine the long-term outcomes.

Otherwise, there is no specific treatment to prevent colon cancer or colon polyps. If colon polyps are found by a colonoscopy, doctors can usually treat them by removing them, however, if there are too many polyps they may not be able to be removed by a colonoscopy. Screening for colon polyps, colon cancer, upper intestinal cancer, and thyroid cancer can be managed through a gastrointestinal specialist (gastroenterologist).

Familial adenomatous polyposis screening recommendations include:

Having familial adenomatous polyposis is a predisposition for developing colon polyps and colon cancer. There is also a predisposition for developing other cancers including: small intestinal cancer, pancreatic cancer, thyroid cancer, and hepatoblastoma (tumor of the liver) in children. Having a mutation in the APC genes does not guarantee someone will develop cancer.

If you have inherited a gene change in the APC gene and have familial adenomatous polyposis, this increases the lifetime risk of developing colon cancer to 100%. There is a 95% lifetime risk of developing colon polyps by the age of 35. The life time risk of developing small intestinal polyps is 50-90%. The lifetime risk for developing desmoid tumors is 10-30%, the life time risk for developing duodenum (upper part of the small intestine) cancer is 4-12%, the life time risk for developing pancreatic cancer is 2%, the lifetime risk for developing a brain tumor is less than 1%, the lifetime risk for developing hepatoblastoma is 1%, and the lifetime risk for developing thyroid cancer is 2%.

If you have inherited a gene change in the MUTYH gene and have MUTYH-associated polyposis, this increases the lifetime risk of developing colon cancer from 43-100%. There is also a 4% increased risk for developing duodenum cancer (cancer in the upper part of the small intestine).

Your doctor should also be aware of the signs and symptoms of colon polyps. Colon polyps often do not cause any symptoms. But, some people with colon polyps may experience rectal bleeding, change in color of the stool (blood may make the stool appear black or it may have red streaks), change in bowel habits including constipation or diarrhea, pain, nausea, vomiting, or iron deficiency.

Your doctor should also be aware of the symptoms of colon cancer, which may include: a change in bowel habits including constipation, diarrhea, or narrowing of the stool, which lasts for more than a few days, feeling that you need to have a bowel movement but the feeling is not relieved by doing so, blood in the stool, rectal bleeding, cramping or abdominal pain, weakness, fatigue, and unintended weight loss.

Your doctor should be aware of the medical management guidelines for familial adenomatous polyposis found on NCCN.com which include:

There are options for family planning in the context of familial adenomatous polyposis. One option is to adopt or use a sperm or egg donor. Another option is to have biological children, and know that there is a 50% risk that each child could inherit this mutation. If the gene mutation causing familial adenomatous polyposis in your family is known,a final option is having preimplantation genetic diagnosis (PGD), which involves in vitro fertilization. Through the process of PGD, embryos can be checked to see if they contain the gene mutation or not, and only embryos that do not contain the mutation will be implanted in the mother.

The colonoscopy procedures depends on your case and your doctor. Your doctor can give you a better idea in your exact situation. The average procedure takes approximately 30 minutes, and you will be in the recovery room afterwards for another 30 minutes.

An ileostomy or colostomy is when a portion of the small intestine or colon is brought out to the skin through a surgical opening of the abdominal wall (stoma). Instead of eliminating with a bowel movement, waste will be passed through into a specially fitted low-profile appliance, known as a pouching system or a bag. Whether or not a patient will require a stoma depends on the nature of their disease. Temporary and even permanent ileostomies are sometimes required after certain operations. If there is rectal cancer that involves or is close to the anal sphincter mechanism, a permanent colostomy could be required. Patients who may require a stoma work closely with a team of nurses to learn how to manage their stoma. Patients with stomas are able to live healthy, active lives and enjoy all of the activities they used to do before they had a stoma.

Because familial adenomatous polyposis (FAP) is inherited in an autosomal dominant inheritance pattern, it means that every first degree relative of an affected individual has a 50% chance of also having it. First degree relatives are siblings, children, and parents. Second degree relatives should have testing after first degree relatives are all tested. in a specific example, let’s say 27-year-old Andrea has been diagnosed with FAP. Andrea has 3 children. EACH of her children has an individual 50% chance to also have it. Andrea has 2 siblings: one brother and one sister. EACH of her siblings has an individual 50% chance to also have it. Andrea’s mother has testing and is negative. This means that Andrea’s mothers side of the family does NOT need to have any more testing. Andrea’s father has testing and is positive. Each of Andrea’s father’s siblings should have testing as well, because they have an individual 50% chance of being positive as well.

A gastroenterologist will use an endoscope (a small tubing that has a tiny camera attached to the end) to go down through the esophagus into the stomach and the first part of the small intestine. This is used to look for any polyps located in the small intestine, stomach, and esophagus.

Usually, for the first 6 weeks after surgery it is recommended to have a low residue diet, which is low in fiber to try to reduce the frequency of stool. The long term effects depend on the amount of the colon removed. If part of the colon is removed, patients may notice little change in their bowel function. If the entire colon is removed, the patient may notice a change in the frequency of their bowels. After you have healed, your doctor will follow your progress and determine when your digestive system is ready to resume normal eating. Even in a situation when the entire colon needs to be removed, you will be able to return to your normal activities with a good quality of life despite the absence of the entire colon.

Familial adenomatous polyposis is usually inherited in an autosomal dominant manner. This means that an individual only needs one mutation in a gene in order to have an increased risk for colon polyps and cancer. If a parent has a mutation, there is a 50% chance that each of their children will inherit the mutation. If an individual has a mutation there is a 50% chance that their siblings also have the mutation. Men and women are equally likely to have these mutations and sons and daughters are equally likely to inherit them.

Sometimes there may not be a family history of FAP and approximately 20-25% of the time, the change in the APC gene is only found in one person who has FAP and not found in any other of their family members. This is called a de novo mutation, which means the change happened for the first time in that individual, and it was not inherited from a family member. However, the mutation can still be passed on to that individual’s children.

MUTYH-associated polyposis is inherited differently. It is inherited in an autosomal recessive manner. This means, an individual needs two mutations in order to have an increased for developing polyps. For someone to inherit two mutations, they would inherit one mutation from their mother and one mutation from their father. In this case, the parents would be considered carriers of MUTYH-associated polyposis. This means that each parent is not at risk to develop colon polyps, however, they are at a slightly increased risk for developing colon cancer. If both parents carry a mutation, each of their children have a 25% chance of having two mutations and having an increased risk for developing colon polyps. Men and women are equally likely to have these mutations and sons and daughters are equally likely to inherit them.

You can start a support group by contacting already existing support groups and asking them how you they started their organization. It is also recommended that you contact a professional who can provide guidance. For more information, view the Global Genes’ Tool kit.

In addition to donating to your local cancer center, you can donate to research funds such as MacMillan Cancer Support (www.macmillan.org.uk), Colon Cancer Alliance (www.ccalliance.org), Live Strong (www.livestrong.org/we-can-help/attenuated-familial-adenomatous-polyposis), Fight Colorectal Cancer (http://fightcolorectalcancer.org), and Hereditary Colon Cancer Takes Guts [link url="www.hcctakesguts.org” target=”_blank”>Hereditary Colon Cancer Takes Guts

Testing for familial adenomatous polyposis can be done through a simple blood test. The type of tests to be ordered by your doctor is called sequencing of the APC gene which is when the "spelling" of the APC gene is checked for errors. They may also order a deletion/duplication analysis of the APC gene that looks for big chunks of the gene that are missing or added that could be missed with sequencing.

For MUTYH-associated polyposis, there are typically two changes in the MUTYH gene that cause this colon polyp predisposition, called c.536A>G (p.Tyr179Cys) and c.1187G>A (p.Gly396Asp). These mutations are carried by approximately 1%-2% of the general population and account for at least 90% of all MUTYH pathogenic variants in northern European populations. Genetic testing would check for these two mutations first to see if the changes are present or not. If that testing is normal, then your doctor may order sequencing of the MUTYH gene where the "spelling" of the MUTYH gene is checked for errors. Deletion/duplication analysis of the MUTYH gene is also available, though there have been very few mutations of this type reported.

These tests are usually ordered by a genetics health provider after genetic counseling which will examine an individual’s personal and family history to determine if genetic testing for the APC and/or MUTYH gene makes sense as opposed to testing for another genetic condition. A genetic counselor focused on cancer in your area can be found at www.nsgc.org website.

The website: www.clinicaltrials.gov gives a list of clinical trials currently underway for familial adenomatous polyposis. You can also go to Center Watch Patient Notification Service, Clinical trials [link url="www.cetnerwatch.com/clinical-trials/pns” target=”_blank”>CenterWatch Patient Notification Service

You can also find clinic research or scientific articles at: www.scholar.google.com and search "familial adenomatous polyposis."

There are several cancer centers that work with individuals with familial adenomatous polyposis, which include: Beth Israel Lahey Health , The Children’s Hospital of Philadelphia, [link url=" http://my.clevelandclinic.org/services/digestive_diseases/departments-centers/colorectal-surgery/weiss-center-hereditary-colorectal-neoplasia ” target=”_blank”>Cleveland Clinic Center for Hereditary Colon Neoplasia, University of Chicago Gastrointestinal Cancer Risk and Prevention Clinic and St. Jude’s Children’s Research Hospital.

Blood is the preferred specimen, but saliva can be used as an alternative as your APC and/or MUTYH genes are most often the same in blood or saliva. Testing is not recommended on a biopsy sample as we would be testing the genetic makeup of the tumor, rather than the cells that are representative of the person’s inherited genetic makeup (germline). Different labs have different specimens that are or are not willing to accept. A genetic counselor focused on cancer who can help with laboratory requirements in your area can be found at www.nsgc.org website.

There are some risk factors that increase the risk for developing colon polyps and colon cancer which include: age, gender (males are more likely to develop colon cancer), a high body mass index (BMI), family history of colon cancer/polyps, alcohol use, smoking, diabetes (Type II is associated with a higher risk), dietary factors (red meats, processed meats, and fat increase risk, whereas fruits, veggies, and fiber decrease risk), ethnicity (African Americans have higher risk to develop colon cancer), having an inflammatory bowel disease (Crohn’s disease or ulcerative colitis), and radiation exposure to the lower abdomen. More information about these risk factors can be through the American Cancer Society webpage.

Colon polyps can become cancerous during the teenage years with familial adenomatous polyposis, however, usually they do not become cancerous until the 20-30’s. Fortunately, early detection of polyps through colonoscopy can help prevent colon cancer from ever developing.

There is no specific treatment to prevent familial adenomatous polyposis. However, there are ways to manage and screen for colon polyps, colon cancer, stomach cancer, thyroid cancer, and other non-cancerous associated features.

Familial adenomatous polyposis screening recommendations include:

Familial adenomatous polyposis can also be called:

Support groups for familial adenomatous polyposis include:

Typically, if an individual has a personal history of more than 100 adenomatous polyps they will test positive for a mutation in the APC gene. If an individual has attenuated FAP, mutations in the APC gene are not always identified, and this suggests that there may be another gene, currently unknown, which may be responsible for the multiple polyps.

There are different forms of familial adenomatous polyposis that can be told apart based on the number of polyps in the colon, other health issues seen in association with the polyps, and/or the gene changes causing the condition. Genes are made up of a combination of different letters, and the order of these letters is important for the gene to function properly. Mutations in the APC gene are responsible for both FAP and milder form, attenuated FAP (AFAP). The APC gene is a very large gene, and mutations towards the center of the APC gene most often cause classic FAP. Whereas, mutations towards the ends of the APC gene usually cause attenuated FAP. Mutations towards the end of the genes have also been associated with a higher risk for developing the non-cancerous features including: osteomas, CHRPE (a spot on the retina of the eye), desmoid (an abnormal growth of tissue), extra teeth, and cysts. Deletions of the entire APC gene or pieces missing from the gene have also been associated with attenuated FAP. There are different mutations in different regions of the gene that have been associated with earlier and later onset polyps.

MUTYH-associated polyposis has a mutation in the MUTYH gene that is responsible for an earlier onset and more severe version of the condition. The mutation is: c.536A>G, which means there is a change in the letter A to G 536 letters into the gene. In general, individuals who have a mutation in the MUTYH gene, associated with MUTYH-associated polyposis, do not always develop colon polyps or colon cancer, and this is known as incomplete penetrance.

When the colon polyps are found with other very specific health problems, familial adenomatous polyposis can be called Gardner or Turcot syndrome. Gardner syndrome has been used in the past to describe individuals with FAP who also have cysts on their face, desmoids, extra teeth, or cysts on their jawline. Turcot syndrome has been used in the past to describe individuals who with FAP, who also have multiple individuals in their family who also have CNS (central nervous system or brain) tumors.

The differential diagnosis for familial adenomatous polyposis includes: