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APC-Associated Polyposis Conditions.

Source

GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2018.
1998 Dec 18 [updated 2017 Feb 2].

Author information

1
Ambry Genetics, Aliso Viejo, California
2
University of Colorado Anschutz Medical Center, Aurora, Colorado
3
Veterans Affairs Hospital, Denver, Colorado
4
Gastroenterology of the Rockies, Denver, Colorado

Excerpt

CLINICAL CHARACTERISTICS:

APC-associated polyposis conditions include: familial adenomatous polyposis (FAP), attenuated FAP, and gastric adenocarcinoma and proximal polyposis of the stomach (GAPPS). FAP is a colon cancer predisposition syndrome in which hundreds to thousands of adenomatous colonic polyps develop, beginning, on average, at age 16 years (range 7-36 years). By age 35 years, 95% of individuals with FAP have polyps; without colectomy, colon cancer is inevitable. The mean age of colon cancer diagnosis in untreated individuals is 39 years (range 34-43 years). Extracolonic manifestations are variably present and include: polyps of the gastric fundus and duodenum, osteomas, dental anomalies, congenital hypertrophy of the retinal pigment epithelium (CHRPE), soft tissue tumors, desmoid tumors, and associated cancers. Attenuated FAP is characterized by multiple colonic polyps (average of 30), more proximally located polyps, and a diagnosis of colon cancer at a later age than in FAP. Certain extracolonic manifestations, such as gastric and duodenal polyps or cancers, are variably present in attenuated FAP; risk management may be substantially different between FAP and attenuated FAP. GAPPS is characterized by gastric fundic gland polyposis, increased risk of gastric cancer, and limited colonic involvement in most individuals reported.

DIAGNOSIS/TESTING:

The diagnosis of an APC-associated polyposis condition is now established by molecular genetic testing. Typically, it is suspected in an individual with suggestive personal and/or family history features and confirmed by identification of a heterozygous germline pathogenic variant in APC.

MANAGEMENT:

Treatment of manifestations: There is an absolute indication for colectomy when colorectal cancer is diagnosed or suspected, or when there are significant symptoms (bleeding/obstruction). Relative indications for colectomy include presence of multiple adenomas larger than 6 mm that cannot be reasonably removed endoscopically, a significant increase in adenoma number between surveillance exams, presence of adenomas with high-grade dysplasia, or inability to adequately survey the colon (e.g., due to innumerous diminutive adenomas or limited access to/compliance with colonoscopy). Several studies have shown that nonsteroidal anti-inflammatory drugs (NSAIDs) have caused regression of adenomas in FAP and decreased the polyp burden, though there are currently no FDA-approved chemopreventive agents for FAP. Endoscopic or surgical removal of duodenal adenomas is considered if polyps exhibit villous change or severe dysplasia, exceed one centimeter in diameter, or cause symptoms. Osteomas may be removed for cosmetic reasons. Desmoid tumors may be surgically excised or treated with NSAIDs, anti-estrogens, cytotoxic chemotherapy, and/or radiation. Surveillance: Colorectal screening beginning at age ten to 12 years for FAP and in late teens for attenuated FAP; esophagogastroduodenoscopy by age 20-30 years or prior to colon surgery; regular physical examinations including thyroid palpation, neurologic examination, and abdominal examination (for desmoids); consider annual thyroid ultrasound imaging for increased risk of thyroid cancer. Consider screening for hepatoblastoma by liver ultrasound and measurement of serum alpha-fetoprotein concentration (until age 5 years). The efficacy of screening for gastric cancer or prophylactic gastrectomy is currently unknown for individuals with GAPPS. Evaluation of relatives at risk: Molecular genetic testing for early identification of at-risk family members improves diagnostic certainty and reduces the need for costly screening procedures in those at-risk family members who have not inherited the pathogenic variant.

GENETIC COUNSELING:

APC-associated polyposis conditions are inherited in an autosomal dominant manner. Approximately 75%-80% of individuals with an APC-associated polyposis condition have an affected parent. Offspring of an affected individual are at a 50% risk of inheriting the pathogenic variant in APC. Prenatal testing and preimplantation genetic diagnosis are possible if a pathogenic variant has been identified in an affected family member.

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