Última actualización:
January 27, 2014
Años publicados: 1986, 1988, 1989, 1991, 1992, 1994, 1995, 1996, 1997, 1998, 1999, 2000, 2001, 2008, 2011, 2014
NORD gratefully acknowledges Randall W. Burt, MD, Professor of Medicine, University of Utah School of Medicine; Senior Director for Prevention and Outreach, Huntsman Cancer Institute, University of Utah and Kory Jasperson, MS, Genetic Counselor, Huntsman Cancer Institute, University of Utah, for assistance in the preparation of this report.
Familial adenomatous polyposis (FAP) is a rare inherited cancer predisposition syndrome characterized by hundreds to thousands of precancerous colorectal polyps (adenomatous polyps). If left untreated, affected individuals inevitably develop cancer of the colon and/or rectum at a relatively young age. FAP is inherited in an autosomal dominant manner and caused by abnormalities (mutations) in the APC gene. Mutations in the APC gene cause a group of polyposis conditions that have overlapping features: familial adenomatous polyposis, Gardner syndrome, Turcot syndrome and attenuated FAP.
Classic FAP is characterized by hundreds to thousands of colorectal adenomatous polyps, with polyps appearing on average at age 16 years. Without colectomy, affected individuals usually develop colorectal cancer by the third or fourth decade of life. FAP is also associated with an increased risk for cancer of the small intestine including the duodenum, and cancer of the thyroid, pancreas, liver (hepatoblatoma), central nervous system (CNS), and bile ducts, although these typically occur in less than 10% of affected individuals.
Individuals with CNS tumors and colorectal polyposis have historically been defined as Turcot syndrome. Two-thirds of cases of Turcot syndrome develop from mutations in the APC gene. The remaining cases develop from mutations in the genes that cause hereditary non-polyposis colorectal cancer (HNPCC) also known as Lynch syndrome. Mutations in the APC gene are more commonly associated with medulloblastoma; mutations in the genes that cause HNPCC are more commonly associated with glioblastoma.
Extracolonic manifestations are variably present in FAP, including polyps of the stomach, duodenum and small bowel; and osteomas (bony growths), dental abnormalities, congenital hypertrophy of the retinal pigment epithelium (CHRPE), and soft tissue tumors including epidermoid cysts, fibromas and desmoid tumors. About 5% of individuals with FAP experience morbidity and/or mortality from desmoid tumors. The term Gardner syndrome is often used when colonic polyposis is accompanied by clinically obvious osteomas and soft tissue tumors.
Attenuated FAP is a variant of familial adenomatous polyposis. The disorder is characterized by an increased risk for colorectal cancer (although lower risk than classical FAP) but with fewer polyps (average of 30) and later age of onset of polyps and cancer than is typically seen in classic FAP. Extra-colonic manifestations are also associated with attenuated FAP.
Familial adenomatous polyposis is caused by germline (present in the first cell of the embryo) mutations in the APC gene and is inherited in an autosomal dominant manner, meaning that on average 50% of children of an affected parent will have the disease passed on to them.
Dominant genetic disorders occur when only a single copy or allele of a specific gene is mutated, thereby causing a particular disease. The abnormal gene can be inherited from either parent or can be the result of a new mutation (gene change) in the affected individual. The risk of passing the abnormal gene from affected parent to offspring is 50% for each pregnancy. The risk is the same for males and females.
Familial adenomatous polyposis affects males and females in equal numbers. It occurs in approximately one in 5,000 to 10,000 individuals in the United States and accounts for about 0.5% of all cases of colorectal cancer. One estimate suggests that familial adenomatous polyposis affects 50,000 American families. According to national registries, familial adenomatous polyposis occurs in 2.29-3.2 per 100,000 individuals.
Classical FAP is diagnosed clinically when an individual has 100 or more adenomatous colorectal polyps (typically occurring by the third decade of life) or fewer than 100 polyps and a relative with FAP. Genetic testing for mutations in the APC gene is available to confirm the diagnosis of FAP and the associated conditions. Younger individuals may have fewer polyps. A diagnosis is made in younger people by the presence of the typical polyps and in immediate relative with FAP or by genetic testing.
Treatment
Partial or complete removal of the colon (colectomy) is usually recommended for individuals with classical FAP at an appropriate age, usually between the late teens and late 30s. Sulindac is a nonsteroidal antiinflammatory drug (NSAID) usually used for arthritis, but is sometimes prescribed for individuals with FAP who have had a colectomy to treat polyps in the remaining rectum. Polyps will almost always regress, but it is uncertain if the cancer risk is changed, so surveillance must be continued.
Removal of duodenal polyps is sometimes recommended if they cause symptoms, are large or contain large numbers of abnormal cells (dysplasia). This is to prevent them from becoming cancerous.
Desmoid tumors are benign, but may cause problems by compressing organs and/or blood vessels in the abdomen. These are treated variously with surgery, NSAIDs, anti-estrogen medications, chemotherapy and/or radiation depending on the details in each case. They are sometimes just followed when they do not grow.
Genetic counseling is recommended for individuals with familial adenomatous polyposis and their at-risk family members. This is very helpful to properly obtain and interpret genetic testing. Affected individuals should be screened clinically and endoscopically on a regular basis in order to identify cancerous and pre-cancerous tumors at an early stage. Colon cancer is virtually always prevented by screening and properly timed colectomy. This is similar for duodenal cancer. Other cancers are usually detected early, rather than prevented.
Prevention therapies (chemoprevention) are presently under study in several institutions. Information on these and other current clinical trials is posted on the Internet at www.clinicaltrials.gov. All studies receiving U.S. government funding, and some supported by private industry, are posted on this government web site.
For information about clinical trials being conducted at the National Institutes of Health (NIH) in Bethesda, MD, contact the NIH Patient Recruitment Office:
Tollfree: (800) 411-1222
TTY: (866) 411-1010
Email: [email protected]
For information about clinical trials sponsored by private sources, contact:
www.centerwatch.com
For information about clinical trials conducted in Europe, contact:
https://www.clinicaltrialsregister.eu/
TEXTBOOKS
Yamada T, Alpers DH, Kalloo AN, Kaplowitz N, Owyang C, Powell, DW. Textbook of Gastroenterology. 5th ed. Wiley-Blackwell; 2008:3712. (6th edition now in press.)
JOURNAL ARTICLES
Jasperson, K W, Tuohy TM, Neklason DW and Burt RW.. Hereditary and familial colon cancer. Gastroenterology. 2010; 138(6): 2044-2058.
Rustgi AK. The genetics of hereditary colon cancer. Genes Dev. 2007;15;21(20):2525-38. Review.
Rowley PT. Inherited susceptibility to colorectal cancer. Annu Rev Med. 2005;56:539-54. Review.
Lynch HT, Shaw TG, Lynch JF. Inherited predisposition to cancer: A historical overview. Am J Med Genet. 2004;15;129C(1):5-22.
van Stolk R, et al., Phase I trial of exisulind (sulindac sulfone, FGN-1 as a chemoprotective agent in patients with familial adenomatous polyposis. Clin Cancer Res. 2000;6:78-89.
Lal G, et al., Familial adenomatous polyposis. Semin Surg Oncol. 2000;18:314-23.
INTERNET
Jasperson KW and Burt, R W. Updated 10/27/11. APC-Associated Polyposis Conditions. In: GeneReviews at Genetests: Medical Genetics Information Resource (database online). Copyright, University of Washington, Seattle. 1997-2011. Available at https://www.genetests.org. Accessed Dec 26, 2013.
National Cancer Institute: Genetics of Colorectal Cancer https://www.cancer.gov/cancertopics/pdq/genetics/colorectal/HealthProfessional/page1 Last modified 12/20/2013. Accessed Dec 26, 2013.
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The Genetic and Rare Diseases Information Center (GARD) has information and resources for patients, caregivers, and families that may be helpful before and after diagnosis of this condition. GARD is a program of the National Center for Advancing Translational Sciences (NCATS), part of the National Institutes of Health (NIH).
View reportOrphanet has a summary about this condition that may include information on the diagnosis, care, and treatment as well as other resources. Some of the information and resources are available in languages other than English. The summary may include medical terms, so we encourage you to share and discuss this information with your doctor. Orphanet is the French National Institute for Health and Medical Research and the Health Programme of the European Union.
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