GAPPS – Gastric Adenocarcinoma and Proximal Polyposis of the Stomach Syndrome in 8 Families Tested at Masaryk Memorial Cancer Institute – Prevention and Prophylactic Gastrectomies

Abstract

Gastric adenocarcinoma and proximal polyposis of the stomach (GAPPS) is a rare variant of familial adenomatous polyposis. It is an autosomal-dominant cancer-predisposition syndrome with massive polyposis of the stomach and a significant risk of gastric adenocarcinoma. Li et al., 2016, described point mutations in the Ying Yang 1 binding site of the APC gene 1B promoter associated with GAPPS syndrome. The first GAPPS syndrome in a Czech family was described in 2016. At Masaryk Memorial Cancer Institute, GAPPS syndrome was dia gnosed in eight families using Sanger sequencing. In all families, one mutation in promoter 1B of APC gene NM_001127511: c.-191T>C was detected. This mutation was not found in any patient with multiple colon polyposis without a detected classic mutation in the APC gene. In total, 24 carriers of this mutation in promoter 1B of the APC gene were detected. Out of those 24 carriers, 20 had massive gastric polyposis with more than 100 fundic glandular polyps dia gnosed between the age of 22 and 65, 5 had already died of adenocarcinoma of the stomach (at the ages of 29, 40, 59, 60 and 64, respectively) and another woman was treated at the age of 29. Two female carriers do not yet have polyposis of the stomach at the ages of 31 and 65, respectively; one female carrier has incipient polyposis at the age of 58. A male carrier does not have any clinical symptoms, gastroscopy was not indicated because of his age. Prophylactic total gastrectomy with D2 lymphadenectomy has already been performed 6 times at Masaryk Memorial Cancer Institute, in 5 cases without adenocarcinoma at the ages of 27, 34, 44, 51 and 66, respectively; in one female carrier adenocarcinoma of the stomach was detected in a histology specimen. Two prophylactic gastrectomies with D1 lymphadenectomy were performed at University Hospital Brno at the ages of 42 and 50, respectively. In the Czech Republic point mutation c.-191T>C (rs879253783) in the 1B promoter of the APC gene is a frequent cause of gastric polyposis with a high risk of gastric adenocarcinoma, even at a young age. Positively tested individuals are recommended to high-risk oncology clinic. A necessary part of the discus sion with the patient is information about a preventive gastrectomy.

Environmental and genetic risk factors for gastric cancer

“…The gene mutations responsible were described by Li et al in 2016 as various point mutations in Exon 1B of the APC gene 49 . Given its recent discovery, data concerning lifetime risk of gastric cancer is sparse, however, in the available literature, risks of 12%–20% have been described 15–18 …”

Mutational landscape of gastric adenocarcinoma in Latin America: A genetic approach for precision medicine

“…36 For GAPPS patients, point pathogenic variants in exon 1B of APC (c.−191T > C, c.−192A > G, and c.−195A > C) have been found in Caucasian. 37 , 38 However, we found no reports from LATAM cohorts exposing germline pathogenic variants for these two syndromes.…”

RareAPCpromoter 1B variants in gastric cancer kindreds unselected for fundic gland polyposis

“…Although several families have been reported in the literature, clinical knowledge of GAPPS is limited. [5][6][7][8][9] Our findings suggest that GAPPS-associated variants are rare among individuals at risk for inherited predisposition to primarily diffuse GC, identified in one kindred with a history of gastric polyposis evaluated retrospectively. Based on current…”