Test
Predictive genetic testing for at-risk patients (i.e., patients with a family history of familial adenomatous polyposis [FAP]) and patients with suspected FAP is required for diagnosis.[9]National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: genetic/familial high-risk assessment: colorectal, endometrial, and gastric [internet publication].
https://www.nccn.org/guidelines/category_2
[12]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 May;91(5):963-82.e2.
https://linkinghub.elsevier.com/retrieve/pii/S0016-5107(20)30054-7
http://www.ncbi.nlm.nih.gov/pubmed/32169282?tool=bestpractice.com
[24]Hyer W, Cohen S, Attard T, et al. Management of familial adenomatous polyposis in children and adolescents: Position paper from the ESPGHAN polyposis working group. J Pediatr Gastroenterol Nutr. 2019 Mar;68(3):428-41.
https://journals.lww.com/jpgn/Fulltext/2019/03000/Management_of_Familial_Adenomatous_Polyposis_in.30.aspx
http://www.ncbi.nlm.nih.gov/pubmed/30585891?tool=bestpractice.com
[28]Poylin VY, Shaffer VO, Felder SI, et al. The American Society of Colon and Rectal Surgeons Clinical Practice Guidelines for the management of inherited adenomatous polyposis syndromes. Dis Colon Rectum. 2024 Feb 1;67(2):213-27.
https://journals.lww.com/dcrjournal/fulltext/2024/02000/the_american_society_of_colon_and_rectal_surgeons.6.aspx
http://www.ncbi.nlm.nih.gov/pubmed/37682806?tool=bestpractice.com
[30]Monahan KJ, Bradshaw N, Dolwani S, et al. Guidelines for the management of hereditary colorectal cancer from the British Society of Gastroenterology (BSG)/Association of Coloproctology of Great Britain and Ireland (ACPGBI)/United Kingdom Cancer Genetics Group (UKCGG). Gut. 2020 Mar;69(3):411-44.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7034349
http://www.ncbi.nlm.nih.gov/pubmed/31780574?tool=bestpractice.com
Most cases of FAP are caused by a germline mutation in the tumour-suppressor gene adenomatous polyposis coli, but some cases result from germline mutations in POLD1, POLE, or GREM1.[16]Yamaguchi K, Komura M, Yamaguchi R, et al. Detection of APC mosaicism by next-generation sequencing in an FAP patient. J Hum Genet. 2015 May;60(5):227-31.
https://www.doi.org/10.1038/jhg.2015.14
http://www.ncbi.nlm.nih.gov/pubmed/25716913?tool=bestpractice.com
[17]Bellido F, Pineda M, Aiza G, et al. POLE and POLD1 mutations in 529 kindred with familial colorectal cancer and/or polyposis: review of reported cases and recommendations for genetic testing and surveillance. Genet Med. 2016 Apr;18(4):325-32.
https://www.doi.org/10.1038/gim.2015.75
http://www.ncbi.nlm.nih.gov/pubmed/26133394?tool=bestpractice.com
[18]Esteban-Jurado C, Garre P, Vila M, et al. New genes emerging for colorectal cancer predisposition. World J Gastroenterol. 2014 Feb 28;20(8):1961-71.
https://www.doi.org/10.3748/wjg.v20.i8.1961
http://www.ncbi.nlm.nih.gov/pubmed/24587672?tool=bestpractice.com
[19]Rohlin A, Eiengård F, Lundstam U, et al. GREM1 and POLE variants in hereditary colorectal cancer syndromes. Genes Chromosomes Cancer. 2016 Jan;55(1):95-106.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5057327
http://www.ncbi.nlm.nih.gov/pubmed/26493165?tool=bestpractice.com
If the pathogenic variant is already known, patients should undergo genetic testing for the identified familial pathogenic variant.[9]National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: genetic/familial high-risk assessment: colorectal, endometrial, and gastric [internet publication].
https://www.nccn.org/guidelines/category_2
Where there are no known pathogenic variants in any polyposis genes, the National Comprehensive Cancer Network (NCCN) recommends germline multigene panel testing.[9]National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: genetic/familial high-risk assessment: colorectal, endometrial, and gastric [internet publication].
https://www.nccn.org/guidelines/category_2
Germline testing is important to differentiate between other aetiologies of adenomatous polyposis (e.g., MUTYH-associated polyposis) for the consideration of extracolonic screening, as well as counselling, risk assessment, and testing of family members.[9]National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: genetic/familial high-risk assessment: colorectal, endometrial, and gastric [internet publication].
https://www.nccn.org/guidelines/category_2
While the identification of a pathogenic variant confirms the diagnosis, FAP should not be excluded even where a pathogenic variant cannot be identified.[24]Hyer W, Cohen S, Attard T, et al. Management of familial adenomatous polyposis in children and adolescents: Position paper from the ESPGHAN polyposis working group. J Pediatr Gastroenterol Nutr. 2019 Mar;68(3):428-41.
https://journals.lww.com/jpgn/Fulltext/2019/03000/Management_of_Familial_Adenomatous_Polyposis_in.30.aspx
http://www.ncbi.nlm.nih.gov/pubmed/30585891?tool=bestpractice.com