Hereditary diffuse gastric cancer

Abstract

Approximately 10% of patients with gastric cancer show familial clustering, and 3% show autosomal dominance and high penetrance. Hereditary diffuse gastric cancer (HDGC) is an autosomal-dominant, inherited cancer syndrome in which affected individuals develop diffuse-type gastric cancer at a young age. Inactivating mutations in the E-cadherin gene CDH1 have been identified in 30% to 50% of patients. CDH1 mutation carriers have an approximately 70% lifetime risk of developing DGC, and affected women carry an additional 20% to 40% risk of developing lobular breast cancer. Because endoscopic surveillance is ineffective in identifying early HDGC, gene-directed prophylactic total gastrectomy currently is offered for CDH1 mutation carriers. In series of asymptomatic individuals undergoing total gastrectomy for CDH1 mutations, the removed stomachs usually contain small foci of early DGC, making surgery not prophylactic but curative.The authors of this review recommend consideration of total gastrectomy in CDH1 mutation carriers at an age 5 years younger than the youngest family member who developed gastric cancer. Individuals who choose not to undergo prophylactic gastrectomy should be followed with biannual chromoendoscopy, and women with CDH1 mutations also should undergo regular surveillance with magnetic resonance imaging studies of the breast. Because of the emergence of gene-directed gastrectomy for HDGC, today, a previously lethal disease is detected by molecular techniques, allowing curative surgery at an early stage.

Role of DNA Methylation in the Development of Diffuse-Type Gastric Cancer

“…HDGC is an autosomal-dominant inherent cancer syndrome, and approximately 30% of individuals with a clinical diagnosis of HDGC harbor germline mutation of CDH1 [31,32]. Among individuals with CDH1 germline mutations, the cumulative risk of advanced gastric cancer by age 80 years is 69% in men and 83% in women [33].…”

Hereditary gastric cancer

“…Alternatively, it has been suggested that total gastrectomy should be considered in CDH1 mutation carriers at an age five years younger than the youngest family member who developed gastric cancer [69].…”

Occult Gastric Cancer Presenting as Hypoxia from Pulmonary Tumor Thrombotic Microangiopathy

“…HDGC is a subgroup of diffuse gastric cancer 22. The average age of onset of HDGC is 38 years, and the CDH1 gene mutation is the only genetic mutation described so far that has been associated with the occurrence of HDGC (25%~50% of cases) 23.…”