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Gastric adenocarcinoma and proximal polyposis of the stomach(GAPPS)

MedGen UID:
1657285
Concept ID:
C4749917
Neoplastic Process
Synonyms: GAPPS; POLYPOSIS, GASTRIC; Polyposis, gastric, Dos Santos and de Magalhaes 1980
SNOMED CT: GAPPS - gastric adenocarcinoma and proximal polyposis of stomach (771474005); Gastric adenocarcinoma and proximal polyposis of stomach (771474005); Familial fundic gland polyposis with gastric cancer (771474005)
Modes of inheritance:
Autosomal dominant inheritance
MedGen UID:
141047
Concept ID:
C0443147
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 heterozygotes. In the context of medical genetics, an autosomal dominant disorder is caused when a single copy of the mutant allele is present. Males and females are affected equally, and can both transmit the disorder with a risk of 50% for each child of inheriting the mutant allele.
 
Gene (location): APC (5q22.2)
 
Monarch Initiative: MONDO:0017790
OMIM®: 619182
Orphanet: ORPHA314022

Disease characteristics

Excerpted from the GeneReview: APC-Associated Polyposis Conditions
APC-associated polyposis conditions include (classic or attenuated) familial adenomatous polyposis (FAP) and gastric adenocarcinoma and proximal polyposis of the stomach (GAPPS). FAP is a colorectal cancer (CRC) predisposition syndrome that can manifest in either classic or attenuated form. Classic FAP is characterized by hundreds to thousands of adenomatous colonic polyps, beginning on average at age 16 years (range 7-36 years). For those with the classic form of FAP, 95% of individuals have polyps by age 35 years; CRC is inevitable without colectomy. The mean age of CRC diagnosis in untreated individuals is 39 years (range 34-43 years). The attenuated form is characterized by multiple colonic polyps (average of 30), more proximally located polyps, and a diagnosis of CRC at a later age than in classic FAP. For those with an attenuated form, there is a 70% lifetime risk of CRC and the mean age of diagnosis is 50-55 years. Extracolonic manifestations are variably present and include polyps of the stomach and duodenum, osteomas, dental abnormalities, congenital hypertrophy of the retinal pigment epithelium (CHRPE), benign cutaneous lesions, desmoid tumors, adrenal masses, and other associated cancers. GAPPS is characterized by proximal gastric polyposis, increased risk of gastric adenocarcinoma, and no duodenal or colonic involvement in most individuals reported. [from GeneReviews]
Authors:
Timothy Yen  |  Peter P Stanich  |  Lisen Axell, et. al.   view full author information

Additional description

From OMIM
Gastric adenocarcinoma and proximal polyposis of the stomach (GAPPS) is characterized by autosomal dominant transmission of fundic gland polyposis (FGP) with occasional hyperplastic and adenomatous polyps, sparing of the gastric antrum, and the development of intestinal-type gastric adenocarcinoma. Colorectal polyposis is not observed, and family history does not include colorectal cancer (Worthley et al., 2012).  http://www.omim.org/entry/619182

Clinical features

From HPO
Abdominal pain
MedGen UID:
7803
Concept ID:
C0000737
Sign or Symptom
An unpleasant sensation characterized by physical discomfort (such as pricking, throbbing, or aching) and perceived to originate in the abdomen.
Melena
MedGen UID:
7523
Concept ID:
C0025222
Pathologic Function
The passage of blackish, tarry feces associated with gastrointestinal hemorrhage. Melena occurs if the blood remains in the colon long enough for it to be broken down by colonic bacteria. One degradation product, hematin, imbues the stool with a blackish color. Thus, melena generally occurs with bleeding from the upper gastrointestinal tract (e.g., stomach ulcers or duodenal ulcers), since the blood usually remains in the gut for a longer period of time than with lower gastrointestinal bleeding.
Gastric adenocarcinoma
MedGen UID:
82961
Concept ID:
C0278701
Neoplastic Process
An adenocarcinoma arising from the stomach glandular epithelium. Gastric carcinoma often produces no specific symptoms when it is superficial and potentially surgically curable, although up to 50% of patients may have nonspecific gastrointestinal complaints such as dyspepsia.
Polyposis of gastric fundus without polyposis coli
MedGen UID:
357403
Concept ID:
C1868001
Neoplastic Process
Multiple polyps in the acid-secreting mucosa of the gastric body and fundus. Fundic gland polyps (FGP) are usually 1 to 5 mm in size, though larger polyps have been found. FGPs are typically sessile, shiny, translucent, pale to pinkish in color (resembling the surrounding mucosa), and often exhibit tiny surface blood vessels. These polyps have characteristically been observed to chunk off or detach entirely at the base when removed with cold forceps, in contrast to other types of gastric polyps.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVGastric adenocarcinoma and proximal polyposis of the stomach

Professional guidelines

PubMed

Zaffaroni G, Mannucci A, Koskenvuo L, de Lacy B, Maffioli A, Bisseling T, Half E, Cavestro GM, Valle L, Ryan N, Aretz S, Brown K, Buttitta F, Carneiro F, Claber O, Blanco-Colino R, Collard M, Crosbie E, Cunha M, Doulias T, Fleming C, Heinrich H, Hüneburg R, Metras J, Nagtegaal I, Negoi I, Nielsen M, Pellino G, Ricciardiello L, Sagir A, Sánchez-Guillén L, Seppälä TT, Siersema P, Striebeck B, Sampson JR, Latchford A, Parc Y, Burn J, Möslein G
Br J Surg 2024 May 3;111(5) doi: 10.1093/bjs/znae070. PMID: 38722804Free PMC Article
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
Oliveira C, Pinheiro H, Figueiredo J, Seruca R, Carneiro F
Lancet Oncol 2015 Feb;16(2):e60-70. doi: 10.1016/S1470-2045(14)71016-2. PMID: 25638682

Curated

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

Zaffaroni G, Mannucci A, Koskenvuo L, de Lacy B, Maffioli A, Bisseling T, Half E, Cavestro GM, Valle L, Ryan N, Aretz S, Brown K, Buttitta F, Carneiro F, Claber O, Blanco-Colino R, Collard M, Crosbie E, Cunha M, Doulias T, Fleming C, Heinrich H, Hüneburg R, Metras J, Nagtegaal I, Negoi I, Nielsen M, Pellino G, Ricciardiello L, Sagir A, Sánchez-Guillén L, Seppälä TT, Siersema P, Striebeck B, Sampson JR, Latchford A, Parc Y, Burn J, Möslein G
Br J Surg 2024 May 3;111(5) doi: 10.1093/bjs/znae070. PMID: 38722804Free PMC Article
Tacheci I, Repak R, Podhola M, Benesova L, Cyrany J, Bures J, Kohoutova D
Best Pract Res Clin Gastroenterol 2021 Mar-Apr;50-51:101728. Epub 2021 Feb 15 doi: 10.1016/j.bpg.2021.101728. PMID: 33975682
Dinarvand P, Davaro EP, Doan JV, Ising ME, Evans NR, Phillips NJ, Lai J, Guzman MA
Arch Pathol Lab Med 2019 Nov;143(11):1382-1398. Epub 2019 May 9 doi: 10.5858/arpa.2018-0570-RA. PMID: 31070935
Colvin H, Yamamoto K, Wada N, Mori M
Surg Oncol Clin N Am 2015 Oct;24(4):765-77. Epub 2015 Jul 26 doi: 10.1016/j.soc.2015.06.002. PMID: 26363540
Carneiro F
Pathologe 2012 Nov;33 Suppl 2:231-4. doi: 10.1007/s00292-012-1677-6. PMID: 23052347

Diagnosis

Zaffaroni G, Mannucci A, Koskenvuo L, de Lacy B, Maffioli A, Bisseling T, Half E, Cavestro GM, Valle L, Ryan N, Aretz S, Brown K, Buttitta F, Carneiro F, Claber O, Blanco-Colino R, Collard M, Crosbie E, Cunha M, Doulias T, Fleming C, Heinrich H, Hüneburg R, Metras J, Nagtegaal I, Negoi I, Nielsen M, Pellino G, Ricciardiello L, Sagir A, Sánchez-Guillén L, Seppälä TT, Siersema P, Striebeck B, Sampson JR, Latchford A, Parc Y, Burn J, Möslein G
Br J Surg 2024 May 3;111(5) doi: 10.1093/bjs/znae070. PMID: 38722804Free PMC Article
Carneiro F
Best Pract Res Clin Gastroenterol 2022 Jun-Aug;58-59:101800. Epub 2022 May 4 doi: 10.1016/j.bpg.2022.101800. PMID: 35988963
Tacheci I, Repak R, Podhola M, Benesova L, Cyrany J, Bures J, Kohoutova D
Best Pract Res Clin Gastroenterol 2021 Mar-Apr;50-51:101728. Epub 2021 Feb 15 doi: 10.1016/j.bpg.2021.101728. PMID: 33975682
Dinarvand P, Davaro EP, Doan JV, Ising ME, Evans NR, Phillips NJ, Lai J, Guzman MA
Arch Pathol Lab Med 2019 Nov;143(11):1382-1398. Epub 2019 May 9 doi: 10.5858/arpa.2018-0570-RA. PMID: 31070935
Colvin H, Yamamoto K, Wada N, Mori M
Surg Oncol Clin N Am 2015 Oct;24(4):765-77. Epub 2015 Jul 26 doi: 10.1016/j.soc.2015.06.002. PMID: 26363540

Therapy

McDuffie LA, Sabesan A, Allgäeuer M, Xin L, Koh C, Heller T, Davis JL, Raffeld M, Miettienen M, Quezado M, Rudloff U
J Clin Pathol 2016 Sep;69(9):826-33. Epub 2016 Jul 12 doi: 10.1136/jclinpath-2016-203746. PMID: 27406052Free PMC Article

Prognosis

Dinarvand P, Davaro EP, Doan JV, Ising ME, Evans NR, Phillips NJ, Lai J, Guzman MA
Arch Pathol Lab Med 2019 Nov;143(11):1382-1398. Epub 2019 May 9 doi: 10.5858/arpa.2018-0570-RA. PMID: 31070935
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
Donner I, Kiviluoto T, Ristimäki A, Aaltonen LA, Vahteristo P
Fam Cancer 2015 Jun;14(2):241-6. doi: 10.1007/s10689-015-9778-z. PMID: 25576241

Clinical prediction guides

Carneiro F
Best Pract Res Clin Gastroenterol 2022 Jun-Aug;58-59:101800. Epub 2022 May 4 doi: 10.1016/j.bpg.2022.101800. PMID: 35988963
Matsumoto C, Iwatsuki M, Iwagami S, Morinaga T, Yamashita K, Nakamura K, Eto K, Kurashige J, Baba Y, Miyamoto Y, Yoshida N, Komohara Y, Baba H
Gastric Cancer 2022 Mar;25(2):473-478. Epub 2021 Sep 23 doi: 10.1007/s10120-021-01253-x. PMID: 34554346
Sugai T, Uesugi N, Habano W, Sugimoto R, Eizuka M, Fujita Y, Osakabe M, Toya Y, Suzuki H, Matsumoto T
Virchows Arch 2020 Dec;477(6):835-844. Epub 2020 Jun 12 doi: 10.1007/s00428-020-02846-0. PMID: 32533343Free PMC Article
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
Beer A, Streubel B, Asari R, Dejaco C, Oberhuber G
Z Gastroenterol 2017 Nov;55(11):1131-1134. Epub 2017 Nov 15 doi: 10.1055/s-0043-117182. PMID: 29141268

Recent systematic reviews

Zaffaroni G, Mannucci A, Koskenvuo L, de Lacy B, Maffioli A, Bisseling T, Half E, Cavestro GM, Valle L, Ryan N, Aretz S, Brown K, Buttitta F, Carneiro F, Claber O, Blanco-Colino R, Collard M, Crosbie E, Cunha M, Doulias T, Fleming C, Heinrich H, Hüneburg R, Metras J, Nagtegaal I, Negoi I, Nielsen M, Pellino G, Ricciardiello L, Sagir A, Sánchez-Guillén L, Seppälä TT, Siersema P, Striebeck B, Sampson JR, Latchford A, Parc Y, Burn J, Möslein G
Br J Surg 2024 May 3;111(5) doi: 10.1093/bjs/znae070. PMID: 38722804Free PMC Article

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    • PubMed
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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

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

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