Phenotypic Spectrum of Gastric Adenocarcinoma and Proximal Polyposis of the Stomach (GAPPS) in Denmark - A Case Series Characterizing the First Danish Families With the APC Promotor 1B Variant c.-191T >C

Sep 30, 2026

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Gastric adenocarcinoma and proximal polyposis of the stomach (GAPPS) is a rare, autosomal dominant gastric cancer syndrome marked by fundic gland polyposis (more than 100) and an elevated risk of gastric cancer, driven by pathogenic variants in the APC promotor 1B region. This case series identifies two Danish families carrying the promotor 1B variant c.-191T>C, with diagnosis confirmed by endoscopic polyposis findings and genetic analysis. The report highlights variable phenotypic expression and the resulting challenges for surveillance and genetic counseling.

LanguageEnglish

CategoryHealthcare

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Introduction

Case Reports in Genetics

Case Report

Family I

Family II

Wiley Case Reports in Genetics Volume 2026, Article ID 4024148, 4 pages [https://doi.org/10.1155/crig/4024148](https://doi.org/10.1155/crig/4024148) Case Series Phenotypic Spectrum of Gastric Adenocarcinoma and Proximal Polyposis ofthe Stomach (GAPPS) in Denmark: A Case Series Characterizing the First Danish Families With the APC Promotor 1B Variant c.-191T >C P. A. Skat-Rørdam , 1 A. M. Jelsig , 1,2 J. G. Karstensen ,2,3 A. H. Petersen ,4 M. B. Madsen ,5 and T. D. Jensen4 1 Department of Clinical Genetics, Copenhagen University Hospital, Rigshospitalet, Denmark 2 Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark 3 Danish Polyposis Registry, Gastrounit, Copenhagen University Hospital –Amager and Hvidovre, Hvidovre, Denmark 4 Department of Clinical Genetics, Vejle Hospital, Vejle, Denmark 5 Department of Genomic Medicine, Copenhagen University Hospital, Rigshospitalet, Denmark Correspondence should be addressed to P. A. Skat-Rørdam; [pskatrordam@gmail.com](pskatrordam@gmail.com) Received 17 April 2025; Revised 30 June 2025; Accepted 18 December 2025 Academic Editor: Balraj Mittal Copyright © 2026 P. A. Skat-Rørdam et al. Case Reports in Genetics published by John Wiley & Sons Ltd. Tis is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. Gastric adenocarcinoma and proximal polyposis ofthe stomach (GAPPS) is a rare autosomal dominantly inherited gastric cancer syndrome that is characterized by fundic gland polyposis of the stomach (> 100) and an increased risk of gastric cancer. Te genetic cause is recognized as a pathogenic variant in the promotor 1B ofthe APC gene. Presently, there are no established clinical criteria, and current guidelines are based on limited evidence. In this report, we identifed two families with GAPPS. Family I hada family history of gastric cancer, and we identifed seven family members with GAPPS. Te diagnosis was verifed by endoscopic fndings of polyposis and genetic analysis identifying a variant in the promotor 1B of the APC gene, NM_ 001127511.3: c. - 191T > C. In Family II, the same pathogenic variant, NM_ 001127511.3: c.-191T > C, was detected as an incidental fnding in a 61-year-old patient with hepatocellular carcinoma, clear cell renal carcinoma, and small cell lung cancer. An esophagogastroduodenoscopy (EGD) at the age of 59 had revealed only one small fundic polyp. Tis is the frst report of patients with GAPPS from Denmark, and it emphasizes the variable phenotypic expression and subsequently the difculty of surveillance and genetic counseling in these patients and their families. Keywords: APC; GAPPS; gastric adenocarcinoma and proximal polyposis ofthe stomach; gastric cancer; gastric polyps; promotor region 1. Introduction Gastric adenocarcinoma and proximal polyposis of the stomach (GAPPS) is a novel and rare gastric cancer syndrome [frst described by](frst described by Worthley et al. in 2012)[ Worthley](frst described by Worthley et al. in 2012)[ et al. in 2012](frst described by Worthley et al. in 2012) [1]. Te syndrome is characterized by fundic gland polyposis of the stomach sparing the antrum (> 100 polyps) and a predisposition to gastric cancer. However, knowledge of the phenotypic spectrum is limited. Te underlying genetic cause have been identifed as single nucleotide variants in the promotor 1B region of the APC gene inherited in an autosomal dominant manner. A pathogenic variant in this region causes a reduced binding of the transcription factor Ying Yang 1 (YY1) and, hence, a reduced activity from the promotor 1B [2]. 2 Case Reports in Genetics Fundic gland polyposis of the stomach is also seen in familial adenomatous polyposis (FAP), but as opposed to FAP, GAPPS presents with minimal to no polyposis of the duodenum and colon [3] . Due to the increased risk of gastric

FAQs

What genetic change defines GAPPS in this case series?

The study reports a pathogenic variant in the APC promotor 1B region, specifically c.-191T>C, detected through genetic analysis.

How were the patients diagnosed as having GAPPS?

Diagnosis was verified by endoscopic findings showing fundic gland polyposis and by genetic testing identifying the APC promotor 1B variant.

Why is surveillance and genetic counseling challenging in GAPPS?

The report emphasizes variable phenotypic expression across affected family members, which complicates establishing consistent clinical criteria and guiding monitoring strategies.

Sep 30, 2026

Uploaded by Jiven