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adenomatous polyposis coli (APC); familial adenomatous polyposis (FAP)

A rare familial disorder characterized by development of large numbers (thousands) of colorectal adenomatous polyps & colorectal carcinoma by age 40. - > 100 colon polyps with multiple biopsies confirming tubular adenoma [10] Epidemiology: - prevalence 1 in 10,000 [2] Genetics: 1) autosomal dominant - aberration of APC gene on chromosome 5q21-22 - deletions - point mutation 2) autosomal recessive - mutation in MUTYH gene (MYH) Clinical manifestations: 1) intestinal manifestations: a) adenomatous polyps involving the colon & rarely terminal ileum & proximal small bowel b) upper GI polyps develop 10 years after colonic polyps c) duodenal ampullary carcinoma 2) gastric polyps, gastric cancer 3) adenomas of the gallbladder (rare) 3) extra-GI manifestations (also see Gardner's syndrome) a) benign 1] mandibular osteomas 2] supernumerary teeth 3] hypertrophy of retinal pigment epithelium 4] desmoid tumors 5] epidermoid cysts, sebaceous cysts b) malignant 1] CNS tumors: medulloblastoma 2] thyroid carcinoma a] follicular thyroid carcinoma b] papillary thyroid carcinoma 3] childhood hepatoblastoma Laboratory: - APC gene mutation - GSTP1 gene + APC gene methylation Special laboratory: 1) colonoscopy 2) upper endoscopy every 1-5 years after colectomy to identify adenomatous polyps of the small intestine & rule out ampullary carcinoma [2,7] Complications: 1) > 95% develop colorectal cancer 2) patients at increased risk of extra-colonic cancers a) gastric cancer b) small intestinal cancer - duodenal ampullary adenocarcinoma c) biliary tract neoplasm d) thyroid carcinoma e) CNS neoplasm Differential diagnosis: - Lynch syndrome Management: 1) screening of family members - annual flexible sigmoidoscopy age 12-40 [2] 2) colectomy before development of colorectal carcinoma 3) upper endoscopy every 1-5 years to identify adenomatous polyps of the small intestine & rule out ampullary carcinoma [2,7] 4) non-steroidal anti-inflammatory agents (NSAIDs) a) may induce regression of colorectal polyps b) unclear whether they may delay the need for colectomy c) sulindac 75-100 mg BID has no effect on development of polyps [4] d) sulindac + erlotinib reduces colorectal polyp burden in patients with familial adenomatous polyposis [8]

Related

A/G-specific adenine DNA glycosylase; mutY homolog; hMYH (MUTYH, MYH) adenocarcinoma of the colon &/or rectum APC gene mutation familial adenomatous polyposis [FAP] gene

Specific

flat adenoma syndrome Gardner's syndrome

General

adenomatous polyposis syndrome hereditary colon cancer syndrome

Properties

ASSOCIATED-NEOPLASM[S]: colorectal adenomatous polyp :SITE gastrointestinal system adenocarcinoma of the colon hepatoblastoma exostosis fibroma osteosarcoma adrenal cortical carcinoma thyroid carcinoma DESMOID bile duct cancer epidermoid cyst

Database Correlations

OMIM correlations

References

  1. Mayo Internal Medicine Board Review, 1998-99, Prakash UBS (ed) Lippincott-Raven, Philadelphia, 1998, pg 171, 309
  2. Medical Knowledge Self Assessment Program (MKSAP) 11, 15, 16, 17, 18, 19. American College of Physicians, Philadelphia 1998, 2009, 2012, 2015, 2018, 2021.
  3. Journal Watch 20(15):118, 2000 Steinbach G et al The effect of celecoxib, a cyclooxygenase-2 inhibitor, in familial adenomatous polyposis. N Engl J Med 342:1946, 2000 PMID: 10874062
  4. Journal Watch 22(9):69, 2002 Giardiello FM et al Primary chemoprevention of familial adenomatous polyposis with sulindac. N Engl J Med 346:1054, 2002 PMID: 11932472 - Chau I & Cunningham D, Cyclooxygenase inhibition in cancer--a blind alley or a new therapeutic reality? N Engl J Med 346:1085, 2002 PMID: 11932478
  5. UpToDate 14.1 http://www.utdol.com
  6. Hegde M, Ferber M, Mao R et al ACMG technical standards and guidelines for genetic testing for inherited colorectal cancer (Lynch syndrome, familial adenomatous polyposis, and MYH-associated polyposis). Genet Med. 2014 Jan;16(1):101-16. PMID: 24310308
  7. Vasen HF, Maslein G, Alonso A et al Guidelines for the clinical management of familial adenomatous polyposis (FAP). Gut. 2008 May;57(5):704-13. PMID: 18194984
  8. Boggs W Sulindac-erlotinib Limits Polyp Burden in Familial Adenomatous Polyposis. Medscape - Feb 13, 2018. https://www.medscape.com/viewarticle/892604 - Samadder NJ, Kuwada SK, Boucher KM et al Association of Sulindac and Erlotinib vs Placebo With Colorectal Neoplasia in Familial Adenomatous Polyposis: Secondary Analysis of a Randomized Clinical Trial. JAMA Oncol. 2018 Feb 8. [Epub ahead of print] PMID: 29423501
  9. ARUP Consult: Familial Adenomatous Polyposis and MUTYH-Associated Polyposis https://arupconsult.com/ati/familial-adenomatous-polyposis-and-mutyh-associated-polyposis
  10. NEJM Knowledge+