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Familial adenomatous polyposis 3(FAP3)

MedGen UID:
902388
•Concept ID:
C4225157
•
Disease or Syndrome
Synonyms: NTHL1-Related Adenomatous Polyposis and Colorectal Cancer; NTHL1-related attenuated familial adenomatous polyposis
Modes of inheritance:
Autosomal recessive inheritance
MedGen UID:
141025
•Concept ID:
C0441748
•
Intellectual Product
Source: Orphanet
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in individuals with two pathogenic alleles, either homozygotes (two copies of the same mutant allele) or compound heterozygotes (whereby each copy of a gene has a distinct mutant allele).
Autosomal recessive inheritance (Orphanet)
 
Gene (location): NTHL1 (16p13.3)
 
Monarch Initiative: MONDO:0014630
OMIM®: 616415
Orphanet: ORPHA454840

Disease characteristics

Excerpted from the GeneReview: NTHL1 Tumor Syndrome
NTHL1 tumor syndrome is characterized by an increased lifetime risk for colorectal cancer (CRC), breast cancer, and colorectal polyposis. Colorectal polyps can be adenomatous, hyperplastic, and/or sessile serrated. Duodenal polyposis has also been reported. Additional cancers reported in individuals with NTHL1 tumor syndrome include endometrial cancer, cervical cancer, urothelial carcinoma of the bladder, meningiomas, unspecified brain tumors, basal cell carcinomas, head and neck squamous cell carcinomas, and hematologic malignancies. The cumulative lifetime risk of developing extracolonic cancer by age 60 years has been estimated at 35% to 78%. [from GeneReviews]
Full text of GeneReview (by section):
Summary  |  Diagnosis  |  Clinical Characteristics  |  Genetically Related (Allelic) Disorders  |  Differential Diagnosis  |  Management  |  Genetic Counseling  |  Resources  |  Molecular Genetics  |  Chapter Notes  |  References
Authors:
Roland P Kuiper  |  Maartje Nielsen  |  Richarda M De Voer, et. al.   view full author information

Additional description

From OMIM
Familial adenomatous polyposis-3 is an autosomal recessive cancer predisposition syndrome characterized by the development of multiple colonic adenomas, often with progression to colorectal cancer. Carcinomas affecting other tissues may also occur, and the carcinomas tend to develop in middle age or late adulthood (summary by Weren et al., 2015). For a discussion of genetic heterogeneity of familial adenomatous polyposis, see FAP1 (175100).  http://www.omim.org/entry/616415

Clinical features

From HPO
Bladder neoplasm
MedGen UID:
594
•Concept ID:
C0005695
•
Neoplastic Process
The presence of a neoplasm of the urinary bladder.
See: Feature record | Search on this feature
Malignant tumor of prostate
MedGen UID:
138169
•Concept ID:
C0376358
•
Neoplastic Process
A cancer of the prostate.
See: Feature record | Search on this feature
Skin basal cell carcinoma
MedGen UID:
1648304
•Concept ID:
C4721806
•
Neoplastic Process
The presence of a basal cell carcinoma of the skin.
See: Feature record | Search on this feature
Endometrial carcinoma
MedGen UID:
96903
•Concept ID:
C0476089
•
Neoplastic Process
A carcinoma of the endometrium, the mucous lining of the uterus.
See: Feature record | Search on this feature
Colon cancer
MedGen UID:
2839
•Concept ID:
C0007102
•
Neoplastic Process
A primary or metastatic malignant neoplasm that affects the colon. Representative examples include carcinoma, lymphoma, and sarcoma.
See: Feature record | Search on this feature
Duodenal adenocarcinoma
MedGen UID:
82985
•Concept ID:
C0278804
•
Neoplastic Process
A malignant epithelial tumor with a glandular organization that originates in the duodenum.
See: Feature record | Search on this feature
Pancreatic adenocarcinoma
MedGen UID:
83800
•Concept ID:
C0281361
•
Neoplastic Process
The presence of an adenocarcinoma of the pancreas.
See: Feature record | Search on this feature
Adenomatous colonic polyposis
MedGen UID:
358118
•Concept ID:
C1868071
•
Finding
Presence of multiple adenomatous polyps in the colon.
See: Feature record | Search on this feature
Meningioma
MedGen UID:
7532
•Concept ID:
C0025286
•
Neoplastic Process
The presence of a meningioma, i.e., a benign tumor originating from the dura mater or arachnoid mater.
See: Feature record | Search on this feature
Breast carcinoma
MedGen UID:
146260
•Concept ID:
C0678222
•
Neoplastic Process
The presence of a carcinoma of the breast.
See: Feature record | Search on this feature
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Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVFamilial adenomatous polyposis 3

Professional guidelines

PubMed

Genetic Predisposition to Colorectal Cancer: How Many and Which Genes to Test?
Rebuzzi F, Ulivi P, Tedaldi G
Int J Mol Sci 2023 Jan 21;24(3) doi: 10.3390/ijms24032137. PMID: 36768460Free PMC Article
Evolving strategies for management of desmoid tumor.
Riedel RF, Agulnik M
Cancer 2022 Aug 15;128(16):3027-3040. Epub 2022 Jun 7 doi: 10.1002/cncr.34332. PMID: 35670122Free PMC Article
ACG clinical guideline: Genetic testing and management of hereditary gastrointestinal cancer syndromes.
Syngal S, Brand RE, Church JM, Giardiello FM, Hampel HL, Burt RW; American College of Gastroenterology
Am J Gastroenterol 2015 Feb;110(2):223-62; quiz 263. Epub 2015 Feb 3 doi: 10.1038/ajg.2014.435. PMID: 25645574Free PMC Article

Curated

UK NICE Clinical Guideline CG118, Colorectal cancer prevention: colonoscopic surveillance in adults with ulcerative colitis, Crohn's disease or adenomas, 2022

American College of Medical Genetics and Genomics, Genomic Testing (Secondary Findings) ACT Sheet, APC Pathogenic Variants (Familial Adenomatous Polyposis [FAP]), 2019

Recent clinical studies

Etiology

Hereditary colorectal, gastric, and pancreatic cancer: comprehensive review.
Seppälä TT, Burkhart RA, Katona BW
BJS Open 2023 May 5;7(3) doi: 10.1093/bjsopen/zrad023. PMID: 37165697Free PMC Article
Evolving strategies for management of desmoid tumor.
Riedel RF, Agulnik M
Cancer 2022 Aug 15;128(16):3027-3040. Epub 2022 Jun 7 doi: 10.1002/cncr.34332. PMID: 35670122Free PMC Article
Cancer Genetics.
Van Cott C
Surg Clin North Am 2020 Jun;100(3):483-498. Epub 2020 Apr 16 doi: 10.1016/j.suc.2020.02.012. PMID: 32402295
Hereditary Colorectal Polyposis and Cancer Syndromes: A Primer on Diagnosis and Management.
Kanth P, Grimmett J, Champine M, Burt R, Samadder NJ
Am J Gastroenterol 2017 Oct;112(10):1509-1525. Epub 2017 Aug 8 doi: 10.1038/ajg.2017.212. PMID: 28786406
ACG clinical guideline: Genetic testing and management of hereditary gastrointestinal cancer syndromes.
Syngal S, Brand RE, Church JM, Giardiello FM, Hampel HL, Burt RW; American College of Gastroenterology
Am J Gastroenterol 2015 Feb;110(2):223-62; quiz 263. Epub 2015 Feb 3 doi: 10.1038/ajg.2014.435. PMID: 25645574Free PMC Article

Diagnosis

Hereditary colorectal, gastric, and pancreatic cancer: comprehensive review.
Seppälä TT, Burkhart RA, Katona BW
BJS Open 2023 May 5;7(3) doi: 10.1093/bjsopen/zrad023. PMID: 37165697Free PMC Article
Evolving strategies for management of desmoid tumor.
Riedel RF, Agulnik M
Cancer 2022 Aug 15;128(16):3027-3040. Epub 2022 Jun 7 doi: 10.1002/cncr.34332. PMID: 35670122Free PMC Article
Cancer Genetics.
Van Cott C
Surg Clin North Am 2020 Jun;100(3):483-498. Epub 2020 Apr 16 doi: 10.1016/j.suc.2020.02.012. PMID: 32402295
Hereditary gastrointestinal cancer.
Hata K, Yamamoto Y, Kiyomatsu T, Tanaka T, Kazama S, Nozawa H, Kawai K, Tanaka J, Nishikawa T, Otani K, Yasuda K, Kishikawa J, Nagai Y, Anzai H, Shinagawa T, Arakawa K, Yamaguchi H, Ishihara S, Sunami E, Kitayama J, Watanabe T
Surg Today 2016 Oct;46(10):1115-22. Epub 2015 Dec 16 doi: 10.1007/s00595-015-1283-3. PMID: 26676416
ACG clinical guideline: Genetic testing and management of hereditary gastrointestinal cancer syndromes.
Syngal S, Brand RE, Church JM, Giardiello FM, Hampel HL, Burt RW; American College of Gastroenterology
Am J Gastroenterol 2015 Feb;110(2):223-62; quiz 263. Epub 2015 Feb 3 doi: 10.1038/ajg.2014.435. PMID: 25645574Free PMC Article

Therapy

Protective Role of Spermidine in Colitis and Colon Carcinogenesis.
Gobert AP, Latour YL, Asim M, Barry DP, Allaman MM, Finley JL, Smith TM, McNamara KM, Singh K, Sierra JC, Delgado AG, Luis PB, Schneider C, Washington MK, Piazuelo MB, Zhao S, Coburn LA, Wilson KT
Gastroenterology 2022 Mar;162(3):813-827.e8. Epub 2021 Nov 10 doi: 10.1053/j.gastro.2021.11.005. PMID: 34767785Free PMC Article
Mouse Models of Human Gastric Cancer Subtypes With Stomach-Specific CreERT2-Mediated Pathway Alterations.
Seidlitz T, Chen YT, Uhlemann H, Schölch S, Kochall S, Merker SR, Klimova A, Hennig A, Schweitzer C, Pape K, Baretton GB, Welsch T, Aust DE, Weitz J, Koo BK, Stange DE
Gastroenterology 2019 Dec;157(6):1599-1614.e2. Epub 2019 Oct 1 doi: 10.1053/j.gastro.2019.09.026. PMID: 31585123Free PMC Article
Small Bowel Adenocarcinoma.
Aparicio T, Zaanan A, Mary F, Afchain P, Manfredi S, Evans TR
Gastroenterol Clin North Am 2016 Sep;45(3):447-57. doi: 10.1016/j.gtc.2016.04.004. PMID: 27546842
Chemoprevention of familial adenomatous polyposis.
Lynch PM
Fam Cancer 2016 Jul;15(3):467-75. doi: 10.1007/s10689-016-9901-9. PMID: 27083160
Vitamin C selectively kills KRAS and BRAF mutant colorectal cancer cells by targeting GAPDH.
Yun J, Mullarky E, Lu C, Bosch KN, Kavalier A, Rivera K, Roper J, Chio II, Giannopoulou EG, Rago C, Muley A, Asara JM, Paik J, Elemento O, Chen Z, Pappin DJ, Dow LE, Papadopoulos N, Gross SS, Cantley LC
Science 2015 Dec 11;350(6266):1391-6. Epub 2015 Nov 5 doi: 10.1126/science.aaa5004. PMID: 26541605Free PMC Article

Prognosis

Evolving strategies for management of desmoid tumor.
Riedel RF, Agulnik M
Cancer 2022 Aug 15;128(16):3027-3040. Epub 2022 Jun 7 doi: 10.1002/cncr.34332. PMID: 35670122Free PMC Article
Surveillance of Duodenal Polyposis in Familial Adenomatous Polyposis: Should the Spigelman Score Be Modified?
Sourrouille I, Lefèvre JH, Shields C, Colas C, Bellanger J, Desaint B, Paye F, Tiret E, Parc Y
Dis Colon Rectum 2017 Nov;60(11):1137-1146. doi: 10.1097/DCR.0000000000000903. PMID: 28991077
Chemoprevention of familial adenomatous polyposis.
Lynch PM
Fam Cancer 2016 Jul;15(3):467-75. doi: 10.1007/s10689-016-9901-9. PMID: 27083160
ACG clinical guideline: Genetic testing and management of hereditary gastrointestinal cancer syndromes.
Syngal S, Brand RE, Church JM, Giardiello FM, Hampel HL, Burt RW; American College of Gastroenterology
Am J Gastroenterol 2015 Feb;110(2):223-62; quiz 263. Epub 2015 Feb 3 doi: 10.1038/ajg.2014.435. PMID: 25645574Free PMC Article
Familial adenomatous polyposis: clinical presentation, detection and surveillance.
Laurent S, Franchimont D, Coppens JP, Leunen K, Macken L, Peeters M, Plomteux O, Polus M, Poppe B, Sempoux C, Tejpar S, Van Den Eynde M, Van Gossum A, Vannoote J, Kartheuser A, Van Cutsem E
Acta Gastroenterol Belg 2011 Sep;74(3):415-20. PMID: 22103047

Clinical prediction guides

Hereditary gastrointestinal carcinomas and their precursors: An algorithm for genetic testing.
Spoto CPE, Gullo I, Carneiro F, Montgomery EA, Brosens LAA
Semin Diagn Pathol 2018 May;35(3):170-183. Epub 2018 Jan 31 doi: 10.1053/j.semdp.2018.01.004. PMID: 29397239
Surveillance of Duodenal Polyposis in Familial Adenomatous Polyposis: Should the Spigelman Score Be Modified?
Sourrouille I, Lefèvre JH, Shields C, Colas C, Bellanger J, Desaint B, Paye F, Tiret E, Parc Y
Dis Colon Rectum 2017 Nov;60(11):1137-1146. doi: 10.1097/DCR.0000000000000903. PMID: 28991077
Chemoprevention of familial adenomatous polyposis.
Lynch PM
Fam Cancer 2016 Jul;15(3):467-75. doi: 10.1007/s10689-016-9901-9. PMID: 27083160
Oral manifestations in patients with familial adenomatous polyposis: A systematic review and meta-analysis.
Almeida FT, Pachêco-Pereira C, Porporatti AL, Flores-Mir C, Leite AF, De Luca Canto G, Guerra EN
J Gastroenterol Hepatol 2016 Mar;31(3):527-40. doi: 10.1111/jgh.13149. PMID: 26331960
ACG clinical guideline: Genetic testing and management of hereditary gastrointestinal cancer syndromes.
Syngal S, Brand RE, Church JM, Giardiello FM, Hampel HL, Burt RW; American College of Gastroenterology
Am J Gastroenterol 2015 Feb;110(2):223-62; quiz 263. Epub 2015 Feb 3 doi: 10.1038/ajg.2014.435. PMID: 25645574Free PMC Article

Recent systematic reviews

Colectomy and desmoid tumours in familial adenomatous polyposis: a systematic review and meta-analysis.
Aelvoet AS, Struik D, Bastiaansen BAJ, Bemelman WA, Hompes R, Bossuyt PMM, Dekker E
Fam Cancer 2022 Oct;21(4):429-439. Epub 2022 Jan 13 doi: 10.1007/s10689-022-00288-y. PMID: 35022961Free PMC Article
Pancreas-Preserving Total Duodenectomy: A Systematic Review.
Cantalejo-Díaz M, Ramia-Ángel JM, Palomares-Cano A, Serradilla-Martín M
Dig Surg 2021;38(3):186-197. Epub 2021 May 17 doi: 10.1159/000515718. PMID: 34000717
Mosaicism in Patients With Colorectal Cancer or Polyposis Syndromes: A Systematic Review.
Jansen AML, Goel A
Clin Gastroenterol Hepatol 2020 Aug;18(9):1949-1960. Epub 2020 Mar 5 doi: 10.1016/j.cgh.2020.02.049. PMID: 32147591Free PMC Article
Oral manifestations in patients with familial adenomatous polyposis: A systematic review and meta-analysis.
Almeida FT, Pachêco-Pereira C, Porporatti AL, Flores-Mir C, Leite AF, De Luca Canto G, Guerra EN
J Gastroenterol Hepatol 2016 Mar;31(3):527-40. doi: 10.1111/jgh.13149. PMID: 26331960
Peutz-Jeghers syndrome: a systematic review and recommendations for management.
Beggs AD, Latchford AR, Vasen HF, Moslein G, Alonso A, Aretz S, Bertario L, Blanco I, Bülow S, Burn J, Capella G, Colas C, Friedl W, Møller P, Hes FJ, Järvinen H, Mecklin JP, Nagengast FM, Parc Y, Phillips RK, Hyer W, Ponz de Leon M, Renkonen-Sinisalo L, Sampson JR, Stormorken A, Tejpar S, Thomas HJ, Wijnen JT, Clark SK, Hodgson SV
Gut 2010 Jul;59(7):975-86. doi: 10.1136/gut.2009.198499. PMID: 20581245

Supplemental Content

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      See practice and clinical guidelines in NCBI Bookshelf. The search results may include broader topics and may not capture all published guidelines. See the FAQ for details.

    Curated

    • NICE, 2022
      UK NICE Clinical Guideline CG118, Colorectal cancer prevention: colonoscopic surveillance in adults with ulcerative colitis, Crohn's disease or adenomas, 2022
    • ACMG ACT, 2019
      American College of Medical Genetics and Genomics, Genomic Testing (Secondary Findings) ACT Sheet, APC Pathogenic Variants (Familial Adenomatous Polyposis [FAP]), 2019

    Reviews

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