Genetic Syndromes Associated with Gastric Cancer

Abstract

Although environmental factors such as Helicobacter pylori, tobacco, and diet are major contributors to the development of gastric cancer (GC) worldwide, it is estimated that up to 5% to 10% of GC cases are due to an underlying hereditary susceptibility caused by germline pathogenic variants. Hereditary diffuse gastric cancer (HDGC) caused by germline pathogenic variants in the CDH1 gene is the principal familial GC syndrome. However, other well-established hereditary gastrointestinal syndromes have been associated with an increased risk of GC. In this review, we will discuss the latest insights and advances in our understanding of GC associated with Lynch syndrome (LS), familial adenomatous polyposis (FAP), gastric adenocarcinoma and proximal polyposis of the stomach (GAPPS), Li-Fraumeni syndrome (LFS), Peutz-Jeghers syndrome (PJS), and juvenile polyposis syndrome (JPS). We will also discuss the emergence of new associations of the homologous recombination pathway genes (BRCA1, BRCA2) with GC.

Keywords: Familial polyposis; GAPPS; Gastric cancer; Juvenile polyposis syndrome; Li-Fraumeni syndrome; Lynch syndrome; Peutz–Jeghers syndrome.