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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
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
Gastric cancer in FAP: a concerning rise in incidence.
Mankaney G, Leone P, Cruise M, LaGuardia L, O'Malley M, Bhatt A, Church J, Burke CA
Fam Cancer 2017 Jul;16(3):371-376. doi: 10.1007/s10689-017-9971-3. PMID: 28185118
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
Current ideas in desmoid tumours.
Sturt NJ, Clark SK
Fam Cancer 2006;5(3):275-85; discussion 287-8. doi: 10.1007/s10689-005-5675-1. PMID: 16998673

Diagnosis

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
The missing heritability of familial colorectal cancer.
Schubert SA, Morreau H, de Miranda NFCC, van Wezel T
Mutagenesis 2020 Jul 11;35(3):221-231. doi: 10.1093/mutage/gez027. PMID: 31605533Free PMC Article
Management of genetically determined colorectal cancer.
Clark SK
Surgeon 2019 Jun;17(3):165-171. Epub 2019 Mar 29 doi: 10.1016/j.surge.2019.03.003. PMID: 30935877
Gastric cancer in FAP: a concerning rise in incidence.
Mankaney G, Leone P, Cruise M, LaGuardia L, O'Malley M, Bhatt A, Church J, Burke CA
Fam Cancer 2017 Jul;16(3):371-376. doi: 10.1007/s10689-017-9971-3. PMID: 28185118
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

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
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
Role of ileostomy in restorative proctocolectomy.
Pellino G, Sciaudone G, Canonico S, Selvaggi F
World J Gastroenterol 2012 Apr 21;18(15):1703-7. doi: 10.3748/wjg.v18.i15.1703. PMID: 22553394Free PMC Article
Clinical cancer genetics: Part I: Gastrointestinal.
Pollock J, Welsh JS
Am J Clin Oncol 2011 Jun;34(3):332-6. doi: 10.1097/COC.0b013e3181dea432. PMID: 20859198
Nutrition considerations surrounding restorative proctocolectomy.
Buckman SA, Heise CP
Nutr Clin Pract 2010 Jun;25(3):250-6. doi: 10.1177/0884533610368708. PMID: 20581318

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
The missing heritability of familial colorectal cancer.
Schubert SA, Morreau H, de Miranda NFCC, van Wezel T
Mutagenesis 2020 Jul 11;35(3):221-231. doi: 10.1093/mutage/gez027. PMID: 31605533Free PMC Article
Gastric cancer in FAP: a concerning rise in incidence.
Mankaney G, Leone P, Cruise M, LaGuardia L, O'Malley M, Bhatt A, Church J, Burke CA
Fam Cancer 2017 Jul;16(3):371-376. doi: 10.1007/s10689-017-9971-3. PMID: 28185118
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
Colorectal tumourigenesis.
Peiser J, Smith A, Bapat B, Stern H
Surg Oncol 1994 Aug;3(4):195-201. doi: 10.1016/0960-7404(94)90034-5. PMID: 7834110

Clinical prediction guides

Papillary thyroid carcinoma with desmoid fibromatosis: a case report and review of literature.
Ramírez Stieben LA, Pozzi D
Rev Fac Cien Med Univ Nac Cordoba 2023 Sep 29;80(3):289-300. doi: 10.31053/1853.0605.v80.n3.40408. PMID: 37773341Free PMC Article
Shortcuts to intestinal carcinogenesis by genetic engineering in organoids.
Maru Y, Onuma K, Ochiai M, Imai T, Hippo Y
Cancer Sci 2019 Mar;110(3):858-866. Epub 2019 Feb 3 doi: 10.1111/cas.13938. PMID: 30637899Free PMC Article
Gastric cancer in FAP: a concerning rise in incidence.
Mankaney G, Leone P, Cruise M, LaGuardia L, O'Malley M, Bhatt A, Church J, Burke CA
Fam Cancer 2017 Jul;16(3):371-376. doi: 10.1007/s10689-017-9971-3. PMID: 28185118
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
Urinary biomarkers for prostate cancer: a review.
Hessels D, Schalken JA
Asian J Androl 2013 May;15(3):333-9. Epub 2013 Mar 25 doi: 10.1038/aja.2013.6. PMID: 23524531Free 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
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
Surveillance for hereditary cancer: does the benefit outweigh the psychological burden?--A systematic review.
Gopie JP, Vasen HF, Tibben A
Crit Rev Oncol Hematol 2012 Sep;83(3):329-40. Epub 2012 Feb 25 doi: 10.1016/j.critrevonc.2012.01.004. PMID: 22366115
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

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    Clinical resources

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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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