Hereditary Diffuse Gastric Cancer: Approaches to Screening, Surveillance, and Treatment

Annu Rev Med. 2021 Jan 27:72:263-280. doi: 10.1146/annurev-med-051019-103216. Epub 2020 Nov 20.


Hereditary diffuse gastric cancer (HDGC) is a cancer syndrome associated with a significant lifetime risk of diffuse gastric cancer (DGC), a malignancy characterized by late clinical presentation and poor prognosis, as well as lobular breast cancer. HDGC is linked to germline pathogenic variants in the E-cadherin gene (CDH1) that are inherited in an autosomal dominant pattern; however, in many families with DGC clustering, no genetic cause has been identified. This review discusses key elements that allow risk assessment of potential inherited DGC susceptibility. We provide a practical overview of the recommendations for surveillance and treatment of individuals at risk and patients with early disease. The review also outlines future research avenues to improve our understanding of the genetic background and natural history of the disease, the endoscopic detection of early lesions, and the outcome of prophylactic surgery in young individuals.

Keywords: E-cadherin; cancer surveillance; genetic testing; hereditary lobular breast cancer; signet ring cell carcinoma.

Publication types

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

MeSH terms

  • Combined Modality Therapy / methods
  • Early Detection of Cancer / methods*
  • Genetic Predisposition to Disease*
  • Humans
  • Stomach Neoplasms / diagnosis
  • Stomach Neoplasms / genetics*
  • Stomach Neoplasms / therapy