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.

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

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

Genetic Testing Information

• Genetic Testing Registry: Desmoid disease, hereditary
• Genetic Testing Registry: Familial adenomatous polyposis 1
• Genetic Testing Registry: Familial multiple polyposis syndrome
• Genetic Testing Registry: Familial adenomatous polyposis 2

Genetic and Rare Diseases Information Center

• Attenuated familial adenomatous polyposis
• Familial adenomatous polyposis
• Gardner syndrome

Patient Support and Advocacy Resources

• National Organization for Rare Disorders (NORD)

Clinical Trials

• ClinicalTrials.gov

Catalog of Genes and Diseases from OMIM

• DESMOID DISEASE, HEREDITARY; DESMD
• FAMILIAL ADENOMATOUS POLYPOSIS 1; FAP1
• FAMILIAL ADENOMATOUS POLYPOSIS 2; FAP2

Scientific Articles on PubMed

• PubMed

• Attard TM, Cuffari C, Tajouri T, Stoner JA, Eisenberg MT, Yardley JH, Abraham SC, Perry D, Vanderhoof J, Lynch H. Multicenter experience with upper gastrointestinal polyps in pediatric patients with familial adenomatous polyposis. Am J Gastroenterol. 2004 Apr;99(4):681-6. doi: 10.1111/j.1572-0241.2004.04115.x. Citation on PubMed
• Baglioni S, Genuardi M. Simple and complex genetics of colorectal cancer susceptibility. Am J Med Genet C Semin Med Genet. 2004 Aug 15;129C(1):35-43. doi: 10.1002/ajmg.c.30023. Citation on PubMed
• Bienz M. APC. Curr Biol. 2003 Mar 18;13(6):R215-6. doi: 10.1016/s0960-9822(03)00152-0. No abstract available. Citation on PubMed
• Cheadle JP, Sampson JR. Exposing the MYtH about base excision repair and human inherited disease. Hum Mol Genet. 2003 Oct 15;12 Spec No 2:R159-65. doi: 10.1093/hmg/ddg259. Epub 2003 Aug 5. Citation on PubMed
• Claes K, Dahan K, Tejpar S, De Paepe A, Bonduelle M, Abramowicz M, Verellen C, Franchimont D, Van Cutsem E, Kartheuser A. The genetics of familial adenomatous polyposis (FAP) and MutYH-associated polyposis (MAP). Acta Gastroenterol Belg. 2011 Sep;74(3):421-6. Citation on PubMed
• 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. doi: 10.1038/sj.onc.1206471. Citation on PubMed
• Jarvinen HJ, Peltomaki P. The complex genotype-phenotype relationship in familial adenomatous polyposis. Eur J Gastroenterol Hepatol. 2004 Jan;16(1):5-8. doi: 10.1097/00042737-200401000-00002. Citation on PubMed
• Knudsen AL, Bisgaard ML, Bulow S. Attenuated familial adenomatous polyposis (AFAP). A review of the literature. Fam Cancer. 2003;2(1):43-55. doi: 10.1023/a:1023286520725. Citation on PubMed
• 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. doi: 10.1016/s1542-3565(04)00286-1. Citation on PubMed
• Lucci-Cordisco E, Risio M, Venesio T, Genuardi M. The growing complexity of the intestinal polyposis syndromes. Am J Med Genet A. 2013 Nov;161A(11):2777-87. doi: 10.1002/ajmg.a.36253. Epub 2013 Oct 3. Citation on PubMed
• Lynch HT, Shaw TG, Lynch JF. Inherited predisposition to cancer: a historical overview. Am J Med Genet C Semin Med Genet. 2004 Aug 15;129C(1):5-22. doi: 10.1002/ajmg.c.30026. Citation on PubMed
• National Cancer Institute: Genetics of Colorectal Cancer
• Rowley PT. Inherited susceptibility to colorectal cancer. Annu Rev Med. 2005;56:539-54. doi: 10.1146/annurev.med.56.061704.135235. Citation on PubMed
• Rustgi AK. The genetics of hereditary colon cancer. Genes Dev. 2007 Oct 15;21(20):2525-38. doi: 10.1101/gad.1593107. Citation on PubMed
• Sampson JR, Dolwani S, Jones S, Eccles D, Ellis A, Evans DG, Frayling I, Jordan S, Maher ER, Mak T, Maynard J, Pigatto F, Shaw J, Cheadle JP. Autosomal recessive colorectal adenomatous polyposis due to inherited mutations of MYH. Lancet. 2003 Jul 5;362(9377):39-41. doi: 10.1016/S0140-6736(03)13805-6. Citation on PubMed
• 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. doi: 10.1056/NEJMoa025283. Citation on PubMed
• Wang L, Baudhuin LM, Boardman LA, Steenblock KJ, Petersen GM, Halling KC, French AJ, Johnson RA, Burgart LJ, Rabe K, Lindor NM, Thibodeau SN. MYH mutations in patients with attenuated and classic polyposis and with young-onset colorectal cancer without polyps. Gastroenterology. 2004 Jul;127(1):9-16. doi: 10.1053/j.gastro.2004.03.070. Erratum In: Gastroenterology. 2004 Nov;127(5):1651. Citation on PubMed