# 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

## TL;DR

This paper describes the first Danish families diagnosed with a rare inherited stomach cancer syndrome called GAPPS, highlighting the genetic variant and variable symptoms.

## Contribution

The study reports the first Danish cases of GAPPS and emphasizes the variability in clinical presentation linked to the APC gene variant c.-191T > C.

## Key findings

- Two Danish families with GAPPS were identified, with seven confirmed cases in one family.
- The APC promotor 1B variant c.-191T > C was found in both families, showing variable phenotypic expression.
- GAPPS patients presented with multiple fundic gland polyps and increased gastric cancer risk.

## Abstract

Gastric adenocarcinoma and proximal polyposis of the 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. The genetic cause is recognized as a pathogenic variant in the promotor 1B of the APC gene. Presently, there are no established clinical criteria, and current guidelines are based on limited evidence. In this report, we identified two families with GAPPS. Family I had a family history of gastric cancer, and we identified seven family members with GAPPS. The diagnosis was verified by endoscopic findings 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 finding 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. This is the first report of patients with GAPPS from Denmark, and it emphasizes the variable phenotypic expression and subsequently the difficulty of surveillance and genetic counseling in these patients and their families.