Hereditary Diffuse Gastric Cancer Syndrome

Abstract

Quiz Ref ID Gastric cancer (GC) is the third most common cause of cancer-related mortality worldwide.¹ The 2 major subtypes, diffuse GC (DGC) and intestinal-type GC, are distinguished by molecular, epidemiologic, and morphologic features.² Although GC is usually sporadic, familial aggregation occurs in approximately 10% of cases.^3,4 Quiz Ref ID Clinically defined hereditary DGC (HDGC) (OMIM #137215) is characterized by early-onset, multigenerational DGC and lobular breast cancer. Clinical criteria for this entity was established by the International Gastric Cancer Linkage Consortium (IGCLC) (Table 1).^5,6 Approximately 40% of HDGC families have germline mutations in CDH1 (E-cadherin) (Ensembl ENSG00000039068; OMIM *192090), and over 100 different pathogenic germline mutations are reported across multiple ethnicities (eTable 1 in the Supplement).