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Familial Adenomatous Polyposis
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This entry is adapted from the peer-reviewed paper https://medlineplus.gov/genetics/condition/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.

genetic conditions

1. Introduction

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.

2. Frequency

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

3. Causes

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 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.

3.1. The Genes Associated with Familial Adenomatous Polyposis

  • APC
  • MUTYH

4. Inheritance

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.

5. Other Names for This Condition

  • adenomatous familial polyposis
  • adenomatous familial polyposis syndrome
  • adenomatous polyposis coli
  • familial multiple polyposis syndrome
  • FAP
  • MYH-associated polyposis

References

  1. Attard TM, Cuffari C, Tajouri T, Stoner JA, Eisenberg MT, Yardley JH, Abraham SC, Perry D, Vanderhoof J, Lynch H. Multicenter experience with uppergastrointestinal polyps in pediatric patients with familial adenomatouspolyposis. Am J Gastroenterol. 2004 Apr;99(4):681-6.
  2. Baglioni S, Genuardi M. Simple and complex genetics of colorectal cancersusceptibility. Am J Med Genet C Semin Med Genet. 2004 Aug 15;129C(1):35-43.Review.
  3. Bienz M. APC. Curr Biol. 2003 Mar 18;13(6):R215-6. Review.
  4. Cheadle JP, Sampson JR. Exposing the MYtH about base excision repair and humaninherited disease. Hum Mol Genet. 2003 Oct 15;12 Spec No 2:R159-65.
  5. 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 adenomatouspolyposis (FAP) and MutYH-associated polyposis (MAP). Acta Gastroenterol Belg.2011 Sep;74(3):421-6. Review.
  6. Crabtree M, Sieber OM, Lipton L, Hodgson SV, Lamlum H, Thomas HJ, Neale K,Phillips RK, Heinimann K, Tomlinson IP. Refining the relation between 'firsthits' and 'second hits' at the APC locus: the 'loose fit' model and evidence for differences in somatic mutation spectra among patients. Oncogene. 2003 Jul3;22(27):4257-65.
  7. Järvinen HJ, Peltomäki P. The complex genotype-phenotype relationship infamilial adenomatous polyposis. Eur J Gastroenterol Hepatol. 2004 Jan;16(1):5-8.
  8. Knudsen AL, Bisgaard ML, Bülow S. Attenuated familial adenomatous polyposis(AFAP). A review of the literature. Fam Cancer. 2003;2(1):43-55. Review.
  9. Lipton L, Tomlinson I. The multiple colorectal adenoma phenotype and MYH, abase excision repair gene. Clin Gastroenterol Hepatol. 2004 Aug;2(8):633-8.Review.
  10. Lucci-Cordisco E, Risio M, Venesio T, Genuardi M. The growing complexity ofthe intestinal polyposis syndromes. Am J Med Genet A. 2013 Nov;161A(11):2777-87. doi: 10.1002/ajmg.a.36253.
  11. 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.
  12. National Cancer Institute: Genetics of Colorectal Cancer
  13. Rowley PT. Inherited susceptibility to colorectal cancer. Annu Rev Med.2005;56:539-54. Review.
  14. Rustgi AK. The genetics of hereditary colon cancer. Genes Dev. 2007 Oct15;21(20):2525-38. Review.
  15. 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. Autosomalrecessive colorectal adenomatous polyposis due to inherited mutations of MYH.Lancet. 2003 Jul 5;362(9377):39-41.
  16. Sieber OM, Lipton L, Crabtree M, Heinimann K, Fidalgo P, Phillips RK, BisgaardML, Orntoft TF, Aaltonen LA, Hodgson SV, Thomas HJ, Tomlinson IP. Multiplecolorectal adenomas, classic adenomatous polyposis, and germ-line mutations inMYH. N Engl J Med. 2003 Feb 27;348(9):791-9.
  17. 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 mutationsin patients with attenuated and classic polyposis and with young-onset colorectalcancer without polyps. Gastroenterology. 2004 Jul;127(1):9-16. Erratum in:Gastroenterology. 2004 Nov;127(5):1651.
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Subjects: Genetics & Heredity
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Nicole Yin
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Update Date: 25 Dec 2020
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