Familial Adenomatous Polyposis

Familial Adenomatous Polyposis

National Organization for Rare Disorders, Inc.

Important

It is possible that the main title of the report Familial Adenomatous Polyposis is not the name you expected. Please check the synonyms listing to find the alternate name(s) and disorder subdivision(s) covered by this report.

Synonyms

  • adenomatous polyposis of the colon (APC)
  • familial multiple polyposis
  • FAP
  • hereditary polyposis coli
  • multiple polyposis of the colon

Disorder Subdivisions

  • attenuated FAP
  • familial adenomatous polyposis
  • Gardner syndrome
  • Turcot syndrome

General Discussion

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. 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.

Symptoms

Classic FAP is characterized by hundreds to thousand 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 forth decade of life. FAP is also associated with an increased risk for cancer of the small intestine including the duodenum,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 or cancer have historically been defined as Turcot syndrome. Two-thirds of cases of Turcot syndrome develop from mutations in the APC gene. The remaining cases of Turcot syndrome 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, 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 than is typically seen in classic FAP. Extra-colonic manifestations are also associated with attenuated FAP.

Causes

Familial adenomatous polyposis is caused by germline mutations in the APC gene and is inherited in an autosomal dominant manner.



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.

Affected Populations

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.

Standard Therapies

Diagnosis

Classic 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. Molecular 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. Sulindac is a nonsteroidal antiinflammatory drug (NSAID) that is sometimes prescribed for individuals with FAP who have had a colectomy to treat polyps in the remaining rectum.



Removal of duodenal polyps is sometimes recommended if they cause symptoms, are large or contain large numbers of abnormal cells (dysplasia).



Desmoid tumors may be treated with surgery, NSAIDs, anti-estrogen medications, chemotherapy and/or radiation depending on the details in each case.



Genetic counseling is recommended for individuals with familial adenomatous polyposis and their at-risk family members. Affected individuals should be screened regularly in order to identify cancerous and pre-cancerous tumors at an early stage.

Investigational Therapies

Information on 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: prpl@cc.nih.gov



For information about clinical trials sponsored by private sources, contact:

www.centerwatch.com

References

TEXTBOOKS

Yamada T, Alpers DH, Kalloo AN, Kaplowitz N, Owyang C, Powell, DW. Textbook of Gastroenterology. 5th ed. Wiley-Blackwell; 2008:3712.



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.



FROM THE 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 http://www.genetests.org. Accessed 12/11.



National Cancer Institute: Genetics of Colorectal Cancer http://www.cancer.gov/cancertopics/pdq/genetics/colorectal/HealthProfessional/page1

Resources

Familial GI Cancer Registry

Mt. Sinai Hospital

Joseph and Wolf Lebovic Health Complex

600 University Avenue

Toronto

Ontario, M5T 3L9

Canada

Tel: 4165964200

Fax: 4165855024

Email: tberk@mtsinai.on.ca

Internet: http://www.mountsinai.on.ca/care/fgicr



Johns Hopkins Hereditary Colorectal Cancer Registry

Johns Hopkins Hospital

1830 East Monument Stree

Room 431

Baltimore, MD 21205

Tel: (410)955-2635

Fax: (410)614-8337

Tel: (888)772-6566

Email: hccregistry@jhmi.edu

Internet: http://www.hopkins-gi.org



American Cancer Society, Inc.

250 Williams NW St

Ste 6000

Atlanta, GA 30303

USA

Tel: (404)320-3333

Tel: (800)227-2345

TDD: (866)228-4327

Internet: http://www.cancer.org



National Cancer Institute

6116 Executive Blvd Suite 300

Bethesda, MD 20892-8322

USA

Tel: (301)435-3848

Tel: (800)422-6237

TDD: (800)332-8615

Email: cancergovstaff@mail.nih.gov

Internet: http://www.cancer.gov



M. D. Anderson Cancer Center Hereditary Colorectal Cancer Registry

Dept of Gastrointestinal Oncology

1515 Holcombe Boulevard

P.O. Box 78

Houston, TX 77030

Tel: (713)792-3245

Fax: (713)745-1163

Tel: (877)632-6789

Email: hcc-editor@mdacc.tmc.edu

Internet: http://www.mdanderson.org/about-us/index.html



OncoLink: The University of Pennsylvania Cancer Center Resource

3400 Spruce Street

2 Donner

Philadelphia, PA 19104-4283

USA

Tel: (215)349-8895

Fax: (215)349-5445

Email: hampshire@uphs.upenn.edu

Internet: http://www.oncolink.upenn.edu



Strang-Cornell Hereditary Colon Cancer Program

428 East 72nd Street

New York, NY 10021

USA

Tel: (212)794-4900

Fax: (212)794-4958

Email: mbertagnolli@partners.org

Internet: http://www.strang.org



Rare Cancer Alliance

1649 North Pacana Way

Green Valley, AZ 85614

USA

Internet: http://www.rare-cancer.org



Genetic and Rare Diseases (GARD) Information Center

PO Box 8126

Gaithersburg, MD 20898-8126

Tel: (301)251-4925

Fax: (301)251-4911

Tel: (888)205-2311

TDD: (888)205-3223

Internet: http://rarediseases.info.nih.gov/GARD/



Madisons Foundation

PO Box 241956

Los Angeles, CA 90024

Tel: (310)264-0826

Fax: (310)264-4766

Email: getinfo@madisonsfoundation.org

Internet: http://www.madisonsfoundation.org



Friends of Cancer Research

1800 M Street NW

Suite 1050 South

Washington, DC 22202

Tel: (202)944-6700

Email: info@focr.org

Internet: http://www.focr.org



Cancer.Net

American Society of Clinical Oncology

2318 Mill Road Suite 800

Alexandria, VA 22314

Tel: (571)483-1780

Fax: (571)366-9537

Tel: (888)651-3038

Email: contactus@cancer.net

Internet: http://www.cancer.net/



Cancer Support Community

1050 17th St NW Suite 500

Washington, DC 20036

Tel: (202)659-9709

Fax: (202)974-7999

Tel: (888)793-9355

Internet: http://www.cancersupportcommunity.org/



Desmoid Tumor Research Foundation

P.O. Box 273

Suffern, NY 10901

Tel: (914)262-6595

Fax: (845)369-8302

Email: marlene@dtrf.org

Internet: http://www.dtrf.org



Lance Armstrong Foundation

2201 E. Sixth Street

Austin, TX 78702

Tel: (512)236-8820

Fax: (512)236-8482

Tel: (877)236-8820

Email: media@livestrong.org

Internet: http://www.livestrong.org



CORE

3 St. Andrews Place

London, NW1 4LB

United Kingdom

Tel: 02074860341

Fax: 02072242012

Email: info@corecharity.org.uk

Internet: http://www.corecharity.org.uk



For a Complete Report

This is an abstract of a report from the National Organization for Rare Disorders, Inc.® (NORD). Cigna members can access the complete report by logging into myCigna.com. For non-Cigna members, a copy of the complete report can be obtained for a small fee by visiting the NORD website. The complete report contains additional information including symptoms, causes, affected population, related disorders, standard and investigational treatments (if available), and references from medical literature. For a full-text version of this topic, see http://www.rarediseases.org/search/rdblist.html.

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