Familial Adenomatous Polyposis

Actionability Adult Summary Report

Secondary Findings in Adult Subjects. Non-diagnostic, excludes newborn screening & prenatal testing/screening.

• Mode(s) of Inheritance: Autosomal Dominant
• Literature Search: 05/13/2014
• Curation Status: Released (1.0.1)

Assertions and Scores

Actionability Assertions

Gene	Condition (MONDO ID)	OMIM ID	Final Assertion
No assertions found.

Actionability Assertion Rationale

• This topic was initially scored prior to development of the process for making actionability assertions. The Actionability Working Group decided to defer making an assertion until after the topic could be reviewed through the update process.

Actionability Scores

Outcome / Intervention Pair	Severity	Likelihood	Effectiveness	Nature of Intervention	Total Score
No scores were found.

Severity of Outcome

Prevalence of the Genetic Condition

Approximately 4.8% of men and women will be diagnosed with colorectal cancer (CRC) in their lifetime. There are an estimated 1.1 million people currently living with CRC in the U.S. Familial adenomatous polyposis (FAP) accounts for ≤1% of CRC cases.

Clinical Features (Signs / symptoms)

FAP is characterized by the development of hundreds to thousands of adenomas in the colorectum; classical FAP is based on the presence of ≥100 polyps. Extracolonic manifestations are variably present and include desmoid tumors and other malignancies.

Natural History (Important subgroups & survival / recovery)

Colorectal adenomatous polyps begin to appear, on average, by age 16. By age 35, 95% of FAP patients have polyps. In virtually all cases, the adenomas will develop into CRC if left untreated. The mean age of CRC diagnosis in untreated individuals is 39 years; 93% of untreated patients develop CRC by age 50.

Likelihood of Outcome

Mode of Inheritance

Autosomal Dominant

Prevalence of Genetic Variants

1-2 in 10000

APC mutations occur in 1 in 10,000 births.

Tier 3

APC mutations can be identified in 80-93% of FAP cases.

Tier 3

Penetrance (Includes any high-risk racial or ethnic subgroups)

>= 40 %

Virtually 100% of untreated individuals with FAP will develop CRC.

Tier 3

Relative Risk (Includes any high-risk racial or ethnic subgroups)

Unknown

No relative risk estimates were identified.

Expressivity

Development of colorectal adenomas is variable, including variability in the number of adenomas within families with the same APC mutation; 50% of patients have polyps by age 15-16, and 95% by 35 years of age. The presence of duodenal adenomas ranges from 33-92%; 26-51% of FAP patients develop stomach polyps.

Tier 3

Intervention Effectiveness

Patient Management

It is recommended that carriers of the APC mutation be referred for genetic counseling, and be followed by a GI specialist.

Tier 2

Prophylactic (procto)colectomy is recommended when the number and size of the polyps impede surveillance of the colon. The chance of rectal carcinoma after ileorectal anastomosis (IRA) is estimated to be 12-43%, depending on endoscopic surveillance. The chance of adenomas in the pouch following ileal pouch-anal anastomosis (IPAA) ranges from 8-62%, depending on surveillance.

Tier 2

Non-aspirin NSAIDs may be effective for reducing the number and size of colorectal polyps and adenomas in individuals with FAP. NSAIDs use has resulted in a 7-30% decrease in rectal polyps following IRA.

Tier 1

Registry-based screening of individuals with FAP has been shown to lead to a reduction in CRC incidence and CRC-related mortality. Odds ratios for CRC incidence following registration range from 0.09-0.44. Odds ratios for CRC-related mortality range from 0.11-0.22.

Tier 1

Surveillance

Endoscopic surveillance for colorectal polyps, adenomas, and/or CRC is recommended annually or semi-annually, until colectomy. CRC incidence was found to be 3-10% among cases identified through surveillance, compared to 50-70% in symptomatic FAP cases.

Tier 2

Regular endoscopic surveillance of the duodenum is advised. However, the efficacy of this surveillance in reducing CRC incidence is not known.

Tier 1

Additional surveillance may include: annual thyroid exam, annual physical exam with a focus on central nervous system disorders, annual abdominal palpation. However, these screening methods have not been shown to be effective in reducing CRC incidence.

Tier 2

Circumstances to Avoid

Nature of Intervention

Nature of Intervention

Endoscopic surveillance is burdensome for individuals.

Context: Adult

Chance to Escape Clinical Detection

General population CRC screening is recommended at age 50. Given the early age of development of adenomas and CRC in FAP patients, general population screening would not allow for prophylactic measures to be taken.

Context: Adult

Tier 1

Gene Condition Association

Gene			Condition Associations
			OMIM Identifier	Primary MONDO Identifier	Additional MONDO Identifiers

References List

Aretz S, Vasen HF, Olschwang S. (2011) Clinical utility gene card for: familial adenomatous polyposis (FAP) and attenuated FAP (AFAP). European journal of human genetics : EJHG. 19(7).

Asano TK, McLeod RS. (2004) Non steroidal anti-inflammatory drugs (NSAID) and Aspirin for preventing colorectal adenomas and carcinomas. The Cochrane database of systematic reviews. CD004079.

Association of Comprehensive Cancer Centres. Hereditary colorectal cancer. Amsterdam, The Netherlands Association of Comprehensive Cancer Centres. Other (2009) URL: https://www.guidelinecentral.com/summaries/hereditary-colorectal-cancer/

Barrow P, Khan M, Lalloo F, Evans DG, Hill J. (2013) Systematic review of the impact of registration and screening on colorectal cancer incidence and mortality in familial adenomatous polyposis and Lynch syndrome. The British journal of surgery. 100(13):1719-31.

Cairns SR, Scholefield JH, Steele RJ, Dunlop MG, Thomas HJ, Evans GD, Eaden JA, Rutter MD, Atkin WP, Saunders BP, Lucassen A, Jenkins P, Fairclough PD, Woodhouse CR. (2010) Guidelines for colorectal cancer screening and surveillance in moderate and high risk groups (update from 2002). Gut. 59(5):666-89.

Church J, Simmang C. (2003) Practice parameters for the treatment of patients with dominantly inherited colorectal cancer (familial adenomatous polyposis and hereditary nonpolyposis colorectal cancer). Diseases of the colon and rectum. 46(8):1001-12.

Colon and Rectum Cancer.. National Cancer Institute, SEER Stat Fact Sheets, US Department of Health and Human Services, National Institutes of Health. 2-24-2014. (2014) URL: https://seer.cancer.gov/statfacts/html/colorect.html

Colorectal Cancer Screening. Other (2013) URL: https://www.google.com/url?q=http://www.nccn.org/professionals/physician_gls/PDF/colorectal_screening.pdf&sa=U&ved=0ahUKEwiXjIKKne7KAhVW8WMKHUGaDQ0QFggEMAA&client=internal-uds-cse&usg=AFQjCNEBO4lGlL14PJhntw-PBiiCaGupJg

Colorectal Cancer Screening. Other (2012) URL: https://www.icsi.org/guidelines__more/catalog_guidelines_and_more/catalog_guidelines/catalog_prevention__screening_guidelines/colorectal/

Colorectal Screening for Cancer Prevention in Asymptomatic Patients. Other (2013) URL: http://www2.gov.bc.ca/assets/gov/health/practitioner-pro/bc-guidelines/colorectal_screening.pdf

Cooper K, Squires H, Carroll C, Papaioannou D, Booth A, Logan RF, Maguire C, Hind D, Tappenden P. (2010) Chemoprevention of colorectal cancer: systematic review and economic evaluation. Health technology assessment (Winchester, England). 14(32):1-206.

Diagnosis and Management of Colorectal Cancer. SIGN (2015) URL: http://www.sign.ac.uk/pdf/sign126.pdf

Dunlop MG. (2002) Guidance on gastrointestinal surveillance for hereditary non-polyposis colorectal cancer, familial adenomatous polypolis, juvenile polyposis, and Peutz-Jeghers syndrome. Gut. 51 Suppl 5(0017-5749):V21-7.

FAMILIAL ADENOMATOUS POLYPOSIS 1; FAP1. Online Medelian Inheritance in Man, OMIM®. Johns Hopkins University, Baltimore, MD. MIM: 175100, (2016) World Wide Web URL: http://omim.org/

Familial adenomatous polyposis. Orphanet encyclopedia, http://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=en&Expert=733

Guidelines for preventive activities in general practice Colorectal cancer (CRC). Other (2012) URL: http://www.racgp.org.au/your-practice/guidelines/redbook/early-detection-of-cancers/colorectal-cancer-%28crc%29/

Ko C, Hyman NH. (2006) Practice parameter for the detection of colorectal neoplasms: an interim report (revised). Diseases of the colon and rectum. 49(3):299-301.

KW Jasperson, RW Burt. APC-Associated Polyposis Conditions. (1998) [Updated Mar 27 2014]. In: RA Pagon, MP Adam, HH Ardinger, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2026. Available from: https://www.ncbi.nlm.nih.gov/books/NBK1345/

Rex DK, Johnson DA, Anderson JC, Schoenfeld PS, Burke CA, Inadomi JM. (2009) American College of Gastroenterology guidelines for colorectal cancer screening 2009 [corrected]. The American journal of gastroenterology. 104(3):739-50.

Sinha A, Tekkis PP, Gibbons DC, Phillips RK, Clark SK. (2011) Risk factors predicting desmoid occurrence in patients with familial adenomatous polyposis: a meta-analysis. Colorectal disease : the official journal of the Association of Coloproctology of Great Britain and Ireland. 13(11):1222-9.

Vasen HF, Moslein G, Alonso A, Aretz S, Bernstein I, Bertario L, Blanco I, Bulow S, Burn J, Capella G, Colas C, Engel C, Frayling I, Friedl W, Hes FJ, Hodgson S, Jarvinen H, Mecklin JP, Moller P, Myrhoi T, Nagengast FM, Parc Y, Phillips R, Clark SK, de Leon MP, Renkonen-Sinisalo L, Sampson JR, Stormorken A, Tejpar S, Thomas HJ, Wijnen J. (2008) Guidelines for the clinical management of familial adenomatous polyposis (FAP). Gut. 57(5):704-13.

Winawer S, Fletcher R, Rex D, Bond J, Burt R, Ferrucci J, Ganiats T, Levin T, Woolf S, Johnson D, Kirk L, Litin S, Simmang C. (2003) Colorectal cancer screening and surveillance: clinical guidelines and rationale-Update based on new evidence. Gastroenterology. 124(2):544-60.