Hereditary Diffuse Gastric Cancer

Gastroenterology. 2023 Apr;164(5):719-735. doi: 10.1053/j.gastro.2023.01.038. Epub 2023 Feb 4.

Abstract

Hereditary diffuse gastric cancer (HDGC) is a dominantly inherited cancer syndrome characterized by a high incidence of diffuse gastric cancer (DGC) and lobular breast cancer (LBC). HDGC is caused by germline mutations in 2 genes involved in the epithelial adherens junction complex, CDH1 and CTNNA1. We discuss the genetics of HDGC and the variability of its clinical phenotype, in particular the variable penetrance of advanced DGC and LBC, both within and between families. We review the pathology of the disease, the mechanism of tumor initiation, and its natural history. Finally, we describe current best practice for the clinical management of HDGC, including emerging genetic testing criteria for the identification of new families, methods for endoscopic surveillance, the complications associated with prophylactic surgery, postoperative quality of life, and the emerging field of HDGC chemoprevention.

Keywords: CDH1; CTNNA1; Cancer Predisposition; Hereditary Diffuse Gastric Cancer.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Breast Neoplasms* / genetics
  • Cadherins / genetics
  • Carcinoma, Lobular*
  • Female
  • Genetic Predisposition to Disease
  • Genetic Testing / methods
  • Germ-Line Mutation
  • Humans
  • Quality of Life
  • Stomach Neoplasms* / diagnosis
  • Stomach Neoplasms* / genetics
  • Stomach Neoplasms* / prevention & control

Substances

  • Cadherins