Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.
ADVANCED SEARCH
Log in
Top
Current Treatment Options in Gastroenterology
Published in: Current Treatment Options in Gastroenterology 2/2021

01-06-2021 | Gastric Cancer | Genetics in Gastroenterology Practice (BW Katona, Section Editor)

Management of Familial Adenomatous Polyposis

Authors: Gautam Mankaney, MD, Carole Macaron, MD, Carol A. Burke, MD

Published in: Current Treatment Options in Gastroenterology | Issue 2/2021

Login to get access

Abstract

Purpose of review

This paper reviews important aspects in the management of individuals with familial adenomatous polyposis (FAP).

Recent findings

Newly discovered germline pathogenic variants (PVs) beyond APC are a rare cause of adenomatous polyposis. The decreasing cost of multi-gene panel testing (MGPT) has broadened the use of commercial panels to enhance the genetic diagnosis of adenomatous polyposis in families where the causative germline PV in APC is not known. We elucidate emerging risks of cancer in FAP particularly gastric cancer and provide best practices to surveillance and cancer prevention in FAP, including dual therapy chemoprevention and trials utilizing novel mechanisms.

Summary

Genetic testing is indicated in individuals with ≥ 10 lifetime adenomas. FAP and MutYH-associated polyposis (MAP) will be the most common germline causes of colorectal adenomatous polyposis. In FAP, upper endoscopy is indicated for surveillance of gastric polyposis and gastric cancer in addition to duodenal polyposis. Novel agents for chemoprevention have been shown to be effective and considered for selective use in patients with FAP.
Literature
1.
Nieuwenhuis MH, Vasen HF. Correlations between mutation site in APC and phenotype of familial adenomatous polyposis (FAP): a review of the literature. Crit Rev Oncol Hematol. 2007;61(2):153–61.PubMedCrossRef
2.
Ying L, Lin S, Baxter MD, et al. Novel APC promoter and exon 1B deletion and allelic silencing in three mutation-negative classic familial adenomatous polyposis families. Genome Med. 2015;7(1):42.CrossRef
3.
Li J, Woods SL, Healey S, Beesley J, Chen X, Lee JS, et al. Point mutations in exon 1B of APC reveal gastric adenocarcinoma and proximal polyposis of the stomach as a familial adenomatous polyposis variant. Am J Hum Genet. 2016;98:830–42.PubMedPubMedCentralCrossRef
4.
Jones S, Emmerson P, Maynard J, Best JM, Jordan S, Williams GT, et al. Biallelic germline mutations in MYH predispose to multiple colorectal adenoma and somatic G:C-->T:A mutations. Hum Mol Genet. 2002;11(23):2961–7.PubMedCrossRef
5.
Vogt S, Jones N, Christian D. Expanded extracolonic tumor spectrum in MUTYH-associated polyposis. Gastroenterol. 2009;137:1976–85.CrossRef
6.
Win AK, Reece JC, Dowty JG, Buchanan DD, Clendenning M, Rosty C, et al. Risk of extracolonic cancers for people with biallelic and monoallelic mutations in MUTYH. Int J Cancer. 2016;139:1557–63.PubMedPubMedCentralCrossRef
7.
Grover S, Kastrinos F, Steyerberg EW, Cook EF, Dewanwala A, Burbidge LA, et al. Prevalence and phenotypes of APC and MUTYH mutations in patients with multiple colorectal adenomas. JAMA. 2012;308(5):485–92.PubMedPubMedCentralCrossRef
8.
9.
10.
Weren RD, Ligtenberg MJ, Kets CM, et al. A germline homozygous mutation in the base-excision repair gene NTHL1 causes adenomatous polyposis and colorectal cancer. Nat Genet. 2015;47(6):668–71.PubMedCrossRef
11.
Palles C, Cazier JB, Howarth KM, et al. Germline mutations affecting the proofreading domains of POLE and POLD1 predispose to colorectal adenomas and carcinomas. Nat Genet. 2013;45(2):136–44.PubMedCrossRef
12.
Adam R, Spier I, Zhao B, Kloth M, Marquez J, Hinrichsen I, et al. Exome sequencing identifies biallelic MSH3 germline mutations as a recessive subtype of colorectal adenomatous polyposis. Am J Hum Genet. 2016;99(2):337–51.PubMedPubMedCentralCrossRef
13.
Marvin ML, Mazzoni SM, Herron CM, et al. AXIN2-associated autosomal dominant ectodermal dysplasia and neoplastic syndrome. Am J Med Genet A. 2011;155A(4):898–902.PubMedCrossRef
14.
McKenna DB, Van Den Akker J, Zhou AY, et al. Identification of a novel GREM1 duplication in a patient with multiple colon polyps. Familial Cancer. 2019;18(1):63–6.PubMedPubMedCentralCrossRef
15.
Pearlman R, Frankel WL, Swanson B, Zhao W, Yilmaz A, Miller K, et al. Prevalence and spectrum of germline cancer susceptibility gene mutations among patients with early-onset colorectal cancer. JAMA Oncol. 2017;3(4):464–47.PubMedPubMedCentralCrossRef
16.
•• Mankaney G, Cruise M, LaGuardia L, et al. Gastric cancer in FAP: a concerning rise in incidence. Familial Cancer. 2017;16(3):371–6 This study describes rising risk of gastric cancer in Western FAP.PubMedCrossRef
17.
Walton SJ, Frayling IM, Clark SK, Latchford A. Gastric tumors in FAP. Familial Cancer. 2017;16(3):363–9.PubMedCrossRef
18.
Leone PJ, Mankaney G, Sarvapelli S, Abushamma S, Lopez R, Cruise M, et al. Endoscopic and histologic features associated with gastric cancer in FAP. Gastrointest Endosc. 2019;89(5):961–8.PubMedCrossRef
19.
Kannathu ND, Mankaney GN, Leone PJ, et al. Worrisome endoscopic feature in the stomach of patients with FAP: the proximal white mucosal patch. Gastrointest Endosc. 2018;88(3):569–70.CrossRef
20.
•• Mankaney G, Cruise M, Sarvepalli S, et al. SPACE (Surveillance for Pathology Associated with Cancer on Endoscopy) criteria to identify high risk gastric polyps in familial adenomatous polyposis. Gastrointest Endosc. 2020;S0016–5107(20):34265–6 This study describes criteria to identify features associated with high-risk pathology in the stomach.
21.
Thiruvengadam SS, Lopez R, O’Malley M, et al. Spigelman stage IV duodenal polyposis does not precede most duodenal cancer cases in patients with familial adenomatous polyposis. Gastrointest Endosc. 2019;89(2):345–354.e2.PubMedCrossRef
22.
Mehta N, Shah RS, Yoon JY, et al. Risks, benefits, and effects on management for biopsy of the papilla in patients with familial adenomatous polyposis. Clin Gastroenterol Hepatol. 2020;S1542-3565(20):30761–8.
23.
Yoon JY, Mehta N, Burke CA. The prevalence and significance of jejunal and duodenal bulb polyposis after duodenectomy in familial adenomatous polyposis: retrospective cohort study. Ann Surg. 2019;Publish Ahead of Print.
24.
Sarvepalli S, Burke CA, Monachese M, Leach BH, Laguardia L, O’Malley M, et al. Natural history of colonic polyposis in young patients with familial adenomatous polyposis. Gastrointest Endosc. 2018;88(4):726–33.PubMedCrossRef
25.
Sarvepalli S, Burke CA, Monachese M, Lopez R, Leach BH, Laguardia L, et al. Web-based model for predicting time to surgery in young patients with familial adenomatous polyposis: an internally validated study. Am J Gastroenterol. 2018;113(12):1881–90.PubMedPubMedCentralCrossRef
26.
Monachese M, Mankaney G, Lopez R, O’Malley M, Laguardia L, Kalady MF, et al. Outcome of thyroid ultrasound screening in FAP patients with a normal baseline exam. Familial Cancer. 2019;18(1):75–82.PubMedCrossRef
27.
Yang J, Gurudu SR, Koptiuch C, et al. American Society for Gastrointestinal Endoscopy guideline on the role of endoscopy in familial adenomatous polyposis syndromes. Gastrointest Endosc. 2020;91(5):963–982.e2.PubMedCrossRef
28.
Giardiello FM, Hamilton SR, Krush AJ, Piantadosi S, Hylind LM, Celano P, et al. Treatment of colonic and rectal adenomas with sulindac in familial adenomatous polyposis. N Engl J Med. 1993;328(18):1313–6.PubMedCrossRef
29.
Giardiello FM, Yang VW, Hylind LM, Krush AJ, Petersen GM, Trimbath JD, et al. Primary chemoprevention of familial adenomatous polyposis with sulindac. N Engl J Med. 2002;346(14):1054–9.PubMedPubMedCentralCrossRef
30.
Debinski HS, Trojan J, Nugent KP, Spigelman AD, Phillips RKS. Effect of sulindac on small polyps in familial adenomatous polyposis. Lancet. 1995;345(8953):855–6.PubMedCrossRef
31.
Nugent KP, Farmer KC, Spigelman AD, et al. Randomized controlled trial of the effect of sulindac on duodenal and rectal polyposis and cell proliferation in patients with familial adenomatous polyposis. Br J Surg. 1993;80(12):1618–9.PubMedCrossRef
32.
Steinbach G, Lynch P, Philips RK, et al. The effect of celecoxib, a cyclooxygenase-2 inhibitor, in familial adenomatous polyposis. N Engl J Med. 2000;342(26):1946–52.PubMedCrossRef
33.
Phillips RK, Wallace MH, Lynch PM, Hawk E, Gordon GB, Saunders BP, et al. A randomised, double blind, placebo controlled study of celecoxib, a selective cyclooxygenase 2 inhibitor, on duodenal polyposis in familial adenomatous polyposis. Gut. 2002;50(6):857–60.PubMedPubMedCentralCrossRef
34.
Burke CA, Phillips R, Berger MF, Li C, Essex MN, Iorga D, et al. Children’s International Polyposis (CHIP) study: a randomized, double-blind, placebo-controlled study of celecoxib in children with familial adenomatous polyposis. Clin Exp Gastroenterol. 2017;10:177–85.PubMedPubMedCentralCrossRef
35.
Burn J, Bishop DT, Chapman PD, Elliott F, Bertario L, Dunlop MG, et al. A randomized placebo-controlled prevention trial of aspirin and/or resistant starch in young people with familial adenomatous polyposis. Cancer Prev Res. 2011;4(5):655–65.CrossRef
36.
Solomon SD, McMurray JJV, Pfeffer MA, et al. Cardiovascular risk associated with celecoxib in a clinical trial for colorectal adenoma prevention. N Engl J Med. 2005;352(11):1071–80.PubMedCrossRef
37.
West NJ, Clark SK, Phillips RK, et al. Eicosapentaenoic acid reduces rectal polyp number and size in familial adenomatous polyposis. Gut. 2010;59(7):918–25.PubMedCrossRef
38.
Ishikawa H, Wakabayashi K, Suzuki S, Mutoh M, Hirata K, Nakamura T, et al. Preventive effects of low-dose aspirin on colorectal adenoma growth in patients with familial adenomatous polyposis: double-blind, randomized clinical trial. Cancer Med. 2013;2(1):50–6.PubMedPubMedCentralCrossRef
39.
Cruz-Correa M, Hylind LM, Hernandez-Marrero J, et al. Efficacy and safety of curcumin in treatment of intestinal adenomas in patients with familial adenomatous polyposis. Gastroenterol. 2018;155(3):668–73.CrossRef
40.
Bussey HJ, DeCosse JJ, Deschner EE, et al. A randomized trial of ascorbic acid in polyposis coli. Cancer. 1982;50(7):1434–9.PubMedCrossRef
41.
DeCosse JJ, Miller HH, Lesser ML, et al. Effect of wheat fiber and vitamins C and E on rectal polyps in patients with familial adenomatous polyposis. J Natl Cancer Inst. 1989;81(17):1290–7.PubMedCrossRef
42.
Lynch PM, Burke CA, Phillips R, Morris JS, Slack R, Wang X, et al. An international randomised trial of celecoxib versus celecoxib plus difluoromethylornithine in patients with familial adenomatous polyposis. Gut. 2016;65(2):286–95.PubMedCrossRef
43.
Burke CA, Dekker E, Lynch P, Samadder NJ, Balaguer F, Hüneburg R, et al. Eflornithine plus sulindac for prevention of progression in familial adenomatous polyposis. N Engl J Med. 2020;383:1028–39.PubMedCrossRef
44.
•• Samadder NJ, Neklason DW, Boucher KM, et al. Effect of sulindac and erlotinib vs placebo on duodenal neoplasia in familial adenomatous polyposis: a randomized clinical trial. JAMA. 2016;315(12):1266–75 This study highlights the efficacy of combination therapy in the management of upper duodenal neoplasia in FAP.PubMedPubMedCentralCrossRef
45.
Samadder NJ, Kuwada SK, Boucher KM, Byrne K, Kanth P, Samowitz W, 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;4(5):671–7.PubMedPubMedCentralCrossRef
46.
Li H, Schut HA, Conran P, et al. Prevention by aspirin and its combination with alpha-difluoromethylornithine of azoxymethane-induced tumors, aberrant crypt foci and prostaglandin E2 levels in rat colon. Carcinogenesis. 1999;20:425–30.PubMedCrossRef
47.
Jacoby RF, Cole CE, Tutsch K, et al. Chemopreventive efficacy of combined piroxicam and difluoromethylornithine treatment of Apc mutant Min mouse adenomas, and selective toxicity against Apc mutant embryos. Cancer Res. 2000;60:1864–70.PubMed
48.
Meyskens FL Jr, McLaren CE, Pelot D, et al. Difluoromethylornithineplus sulindac for the prevention of sporadic colorectal adenomas: a randomized placebo-controlled, double-blind trial. Cancer Prev Res. 2008;1(1):32–8.CrossRef
49.
Bohan PM, Mankaney G, Vreeland TJ, et al. Chemoprevention in familial adenomatous polyposis: past, present, and future. Familial Cancer. 2020;8:1–11.
50.
Kariv R, Caspi M, Fliss-Isakov N, et al. Resorting the function of the colorectal cancer gatekeeper adenomatous polyposis coli. Int J Cancer. 2020;146(4):1064–74.PubMedCrossRef
Metadata
Title
Management of Familial Adenomatous Polyposis
Authors
Gautam Mankaney, MD
Carole Macaron, MD
Carol A. Burke, MD
Publication date
01-06-2021
Publisher
Springer US
Published in
Current Treatment Options in Gastroenterology / Issue 2/2021
Print ISSN: 1092-8472
Electronic ISSN: 1534-309X
DOI
https://doi.org/10.1007/s11938-020-00324-9

Other articles of this Issue 2/2021

Current Treatment Options in Gastroenterology 2/2021 Go to the issue

Colon (JC Anderson, Section Editor)

Reproductive Health in IBD Patients

Endoscopy (P Siersema, Section Editor)

Diagnosis and Management of Epithelial Precancerous Conditions and Lesions in the Stomach

Endoscopy (P Siersema, Section Editor)

EUS-FNA vs EUS-FNB for Pancreatic Lesions: Which Needle When to Use?

Liver (J Bajaj, Section Editor)

Strategies to Improve Delivery of Cirrhosis Care

Liver (J Bajaj, Section Editor)

Metabolomics in Advanced Liver Disease

Nutrition and Obesity (O Pickett-Blakeley, Section Editor)

Treatment of Micronutrient Deficiencies Pre and Post Bariatric Surgery
Obesity Clinical Trial Summary

At a glance: The STEP trials

Read more

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Pediatric Cardiology Video

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

Cardiopulmonary Comorbidity Video

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Valvular Heart Disease Video

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Heart Failure Video

Watch this official video from ACC.24. Dr. Biykem Bozkurt discuss last year's major advances in heart failure and cardiomyopathies.

ACC 2024 Congress Coverage

Heart Failure Video

Year in Review: Heart failure and cardiomyopathies

Watch now

Watch this official video from ACC.24. Dr. Biykem Bozkurt discuss last year's major advances in heart failure and cardiomyopathies.

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

16-04-2024 Type 2 Diabetes News

Incentivised to exercise

11-04-2024 Lifestyle Modifications News

New intervention for STEMI-related cardiogenic shock

10-04-2024 Myocardial Infarction News

» View more highlights on the ACC 2024 congress hub page

Image Credits