Familial adenomatous polyposis

Reviewed April 2008

What is familial adenomatous polyposis?

Familial adenomatous polyposis (FAP) is an inherited disorder characterized by cancer of the large intestine (colon) and rectum. People with the classic type of familial adenomatous polyposis may begin to develop multiple noncancerous (benign) growths (polyps) in the colon as early as their teenage years. Unless the colon is removed, these polyps will become malignant (cancerous). The average age at which an individual develops colon cancer in classic familial adenomatous polyposis is 39 years. Some people have a variant of the disorder, called attenuated familial adenomatous polyposis, in which polyp growth is delayed. The average age of colorectal cancer onset for attenuated familial adenomatous polyposis is 55 years.

In people with classic familial adenomatous polyposis, the number of polyps increases with age, and hundreds to thousands of polyps can develop in the colon. Also of particular significance are noncancerous growths called desmoid tumors. These fibrous tumors usually occur in the tissue covering the intestines and may be provoked by surgery to remove the colon. Desmoid tumors tend to recur after they are surgically removed. In both classic familial adenomatous polyposis and its attenuated variant, benign and malignant tumors are sometimes found in other places in the body, including the duodenum (a section of the small intestine), stomach, bones, skin, and other tissues. People who have colon polyps as well as growths outside the colon are sometimes described as having Gardner syndrome.

A milder type of familial adenomatous polyposis, called autosomal recessive familial adenomatous polyposis, has also been identified. People with the autosomal recessive type of this disorder have fewer polyps than those with the classic type. Fewer than 100 polyps typically develop, rather than hundreds or thousands. The autosomal recessive type of this disorder is caused by mutations in a different gene than the classic and attenuated types of familial adenomatous polyposis.

How common is familial adenomatous polyposis?

The reported incidence of familial adenomatous polyposis varies from 1 in 7,000 to 1 in 22,000 individuals.

What genes are related to familial adenomatous polyposis?

Mutations in the APC gene cause both classic and attenuated familial adenomatous polyposis. These mutations affect the ability of the cell to maintain normal growth and function. Cell overgrowth resulting from mutations in the APC gene leads to the colon polyps seen in familial adenomatous polyposis. Although most people with mutations in the APC gene will develop colorectal cancer, the number of polyps and the time frame in which they become malignant depend on the location of the mutation in the gene.

Mutations in the MUTYH gene cause autosomal recessive familial adenomatous polyposis (also called MYH-associated polyposis). Mutations in this gene prevent cells from correcting mistakes that are made when DNA is copied (DNA replication) in preparation for cell division. As these mistakes build up in a person's DNA, the likelihood of cell overgrowth increases, leading to colon polyps and the possibility of colon cancer.

How do people inherit familial adenomatous polyposis?

Familial adenomatous polyposis can have different inheritance patterns.

When familial adenomatous polyposis results from mutations in the APC gene, it is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. In most cases, an affected person has one parent with the condition.

When familial adenomatous polyposis results from mutations in the MUTYH gene, it is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. Most often, the parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but do not show signs and symptoms of the condition.

Where can I find information about treatment for familial adenomatous polyposis?

You may find information on treatment or management of familial adenomatous polyposis or some of its symptoms in the links below, particularly the links for Gene Reviews, MedlinePlus Encyclopedia, Educational resources, and Patient support.

Where can I find additional information about familial adenomatous polyposis?

You may find the following resources about familial adenomatous polyposis helpful. These materials are written for the general public.

MedlinePlus - Health information
- Encyclopedia: Colon Cancer (http://www.nlm.nih.gov/medlineplus/ency/article/000262.htm)
- Encyclopedia: Colorectal polyps (http://www.nlm.nih.gov/medlineplus/ency/article/000266.htm)
- Health Topic: Cancer--Living with Cancer (http://www.nlm.nih.gov/medlineplus/cancerlivingwithcancer.html)
- Health Topic: Colorectal Cancer (http://www.nlm.nih.gov/medlineplus/colorectalcancer.html)
Additional NIH Resources - National Institutes of Health
- National Cancer Institute: Colon and Rectal Cancer (http://www.cancer.gov/cancertopics/types/colon-and-rectal)
- National Cancer Institute: Genetics of Colorectal Cancer (http://www.cancer.gov/cancertopics/pdq/genetics/colorectal/HealthProfessional/page1)
- National Human Genome Research Institute: Learning About Colon Cancer (http://www.genome.gov/10000466)
- National Institute of Diabetes and Digestive and Kidney Diseases: Colon Polyps (http://digestive.niddk.nih.gov/ddiseases/pubs/colonpolyps_ez/index.htm)
- NIH Senior Health: Colorectal Cancer (http://nihseniorhealth.gov/colorectalcancer/toc.html)
Educational resources - Information pages
- American Cancer Society: Colon and Rectum Cancer (http://www.cancer.org/docroot/CRI/CRI_2_1x.asp?rnav=criov&dt=10)
- CDC: Colorectal (Colon) Cancer (http://www.cdc.gov/cancer/colorectal/)
- Genetic Science Learning Center, University of Utah (http://learn.genetics.utah.edu/content/disorders/whataregd/colon/index.html)
- Johns Hopkins Cancer Risk Assessment Program: Polyposis and the MYH Gene (http://www.macgn.org/factsheets/Polyposis%20and%20MYH%201.pdf)
- Madisons Foundation (http://www.madisonsfoundation.org/index.php/component/option,com_mpower/diseaseID,381/)
- Mayo Clinic (http://www.mayoclinic.org/familial-adenomatous-polyposis/index.html)
- Mount Sinai Hospital Kid's Corner: FAP & You (http://www.mountsinai.on.ca/care/fgicr/kidskorner/fap)
- National Organization for Rare Disorders (http://www.rarediseases.org/search/rdbdetail_abstract.html?disname=Familial+Adenomatous+Polyposis)
- New York Online Access to Health: Colon, Rectal and Anal Cancer (http://www.noah-health.org/en/cancer/types/colon/)
- Orphanet (http://www.orpha.net//consor/cgi-bin/OC_Exp.php?Lng=EN&Expert=733)
- Wellcome Trust (http://genome.wellcome.ac.uk/doc_WTD023622.html)
Patient support - For patients and families
- American Society of Colon and Rectal Surgeons : Inherited Colorectal Cancer Registries (http://www.fascrs.org/patients/family_history_registries/)
- Colon Cancer Alliance (http://www.ccalliance.org)
- Colorectal Cancer Coalition (http://fightcolorectalcancer.org)

You may also be interested in these resources, which are designed for healthcare professionals and researchers.

Gene Reviews - Clinical summary (http://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=gene&part=fap)
Gene Tests - DNA tests ordered by healthcare professionals
- Gene Tests: Familial Adenomatous Polyposis (http://www.genetests.org/query?testid=2144)
- Gene Tests: Familial Adenomatous Polyposis Autosomal Recessive (http://www.genetests.org/query?testid=213916)
Genetic Tools - Teaching cases (http://www.genetests.org/servlet/access?fcn=y&filename=/tools/cases/colorectal-9/)
ClinicalTrials.gov - Linking patients to medical research (http://clinicaltrials.gov/search/condition=%22familial+adenomatous+polyposis%22)
PubMed - Recent literature (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?CMD=search&DB=PubMed&term=(Adenomatous+Polyposis+Coli[MAJR])+AND+((familial+adenomatous+polyposis[TI])+AND+(FAP[TIAB])+AND+(colorectal))+AND+english[la]+AND+human[mh]&orig_db=PubMed&filters=ON&pmfilter_EDatLimit=720+Days)
OMIM - Genetic disorder catalog
- OMIM topic: Adenomatous Polyposis of the Colon (http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=175100)
- OMIM topic: Colorectal Adenomatous Polyposis, Autosomal Recessive (http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=608456)
- OMIM topic: Hereditary Desmoid Disease (http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=135290)

What other names do people use for familial adenomatous polyposis?

Adenomatous Polyposis Coli
Adenomatous Polyposis of the Colon
Colon cancer, familial
Familial intestinal polyposis
Familial Multiple Polyposis
Familial multiple polyposis syndrome
Familial Polyposis Coli
Familial Polyposis Syndrome
FAP
Hereditary Polyposis Coli
MYH-associated polyposis
Polyposis coli

See How are genetic conditions and genes named? (http://ghr.nlm.nih.gov/handbook/mutationsanddisorders/naming) in the Handbook.

What if I still have specific questions about familial adenomatous polyposis?

See How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.
Ask the Genetic and Rare Diseases Information Center (http://rarediseases.info.nih.gov/GARD/).
Submit your question to Ask the Geneticist (http://www.askthegen.org/).

What glossary definitions help with understanding familial adenomatous polyposis?

autosomal ; autosomal dominant ; autosomal recessive ; benign ; cancer ; cell ; cell division ; colon ; colon polyp ; colorectal ; desmoid ; DNA ; DNA replication ; duodenum ; familial ; gene ; incidence ; inheritance ; inheritance pattern ; intestine ; mutation ; polyp ; polyposis ; recessive ; rectum ; sign ; stomach ; surgery ; symptom ; syndrome ; teenage ; tissue ; tumor

You may find definitions for these and many other terms in the Genetics Home Reference Glossary (http://ghr.nlm.nih.gov/glossary).

References

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Bienz M. APC. Curr Biol. 2003 Mar 18;13(6):R215-6. Review. No abstract available. (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=retrieve&db=pubmed&dopt=Abstract&list_uids=12646143)
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Crabtree M, Sieber OM, Lipton L, Hodgson SV, Lamlum H, Thomas HJ, Neale K, Phillips RK, Heinimann K, Tomlinson IP. Refining the relation between 'first hits' and 'second hits' at the APC locus: the 'loose fit' model and evidence for differences in somatic mutation spectra among patients. Oncogene. 2003 Jul 3;22(27):4257-65. (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=retrieve&db=pubmed&dopt=Abstract&list_uids=12833148)
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Knudsen AL, Bisgaard ML, Bulow S. Attenuated familial adenomatous polyposis (AFAP). A review of the literature. Fam Cancer. 2003;2(1):43-55. Review. (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=retrieve&db=pubmed&dopt=Abstract&list_uids=14574166)
Lipton L, Tomlinson I. The multiple colorectal adenoma phenotype and MYH, a base excision repair gene. Clin Gastroenterol Hepatol. 2004 Aug;2(8):633-8. (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=retrieve&db=pubmed&dopt=Abstract&list_uids=15290654)
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National Cancer Institute: Genetics of Colorectal Cancer (http://www.cancer.gov/cancertopics/pdq/genetics/colorectal/HealthProfessional/page1)
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Sieber OM, Lipton L, Crabtree M, Heinimann K, Fidalgo P, Phillips RK, Bisgaard ML, Orntoft TF, Aaltonen LA, Hodgson SV, Thomas HJ, Tomlinson IP. Multiple colorectal adenomas, classic adenomatous polyposis, and germ-line mutations in MYH. N Engl J Med. 2003 Feb 27;348(9):791-9. (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=retrieve&db=pubmed&dopt=Abstract&list_uids=12606733)
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The resources on this site should not be used as a substitute for professional medical care or advice. Users seeking information about a personal genetic disease, syndrome, or condition should consult with a qualified healthcare professional. See How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.



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