Exame
O teste genético preditivo para pacientes com risco (isto é, pacientes com história familiar de polipose adenomatosa familiar [PAF]) e pacientes com suspeita de PAF é necessário para o diagnóstico.[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
A maioria dos casos de PAF são causados por uma mutação das linhas germinativas no gene supressor tumoral polipose adenomatosa do cólon, mas alguns casos resultam de mutação das linhas germinativas em POLD1, POLE ou 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
Se a variante patogênica já for conhecida, os pacientes devem ser submetidos a testes genéticos para a variante patogênica familiar identificada.[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
Quando não há nenhuma variante patogênica conhecida em qualquer gene da polipose, a National Comprehensive Cancer Network (NCCN) recomenda o teste do perfil multigênico de linha germinativa.[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
O teste de linha germinativa é importante para diferenciar entre outras etiologias de polipose adenomatosa (por exemplo, polipose associada a MUTYH) para a consideração de rastreamento extracolônico, bem como aconselhamento, avaliação de risco e testagem de familiares.[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
Embora a identificação de uma variante patogênica confirme o diagnóstico, a PAF não deve ser descartada mesmo quando uma variante patogênica não for identificada.[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