Hereditary diffuse gastric cancer (HDGC): Clinical characteristics of a prospective cohort of HDGC patients with and without CDH1 mutation and patients with sporadic GC

Abstract

4543 Background: HDGC is an autosomal dominant cancer syndrome associated with early onset diffuse GC. Germline mutations in E-cadherin(CDH1) cause the disease but are identified in only 20–30% of pts meeting clinical criteria. We began a prospective multicenter GC registry to capture epidemiologic and family history data matched with DNA and tissue to characterize phenotypic and risk factor profiles and their associations with HDGC and other non-HDGC hereditable GC. Herein, we report the clinical characteristics of HDGC, the subset of HDGC pts with CDH1 mutation, pts with sporadic GC, and non-cancer controls. Methods: All patients with GC are eligible for registry participation. HDGC criteria: diffuse GC(< age 45), diffuse GC(< age 50) with 1 relative with GC, diffuse GC(any age) with 2 or more relatives with GC, or a personal or family history of diffuse GC with lobular breast cancer or signet ring colon cancer. Non-HDGC high risk pts: diagnosed < age 50 or with a family history of GC(at least one 1st degree or two 2nd degree relatives with GC), but do not meet HDGC criteria. Sporadic GC: diagnosed > age 50, without family history. Participants complete a family history and epidemiology/ risk factor questionnaire, and provide blood and tissue for repository. Results: 465 participants have enrolled since Jan 2006. Questionnaires are available from 331 participants(69%), see table . CDH1 mutations have been identified in 10 families(16%) and prophylactic gastrectomies in CDH1 mutation carriers have been performed in 8 pts, each without major complications. Pt demographics and epidemiology were not notably different amongst all groups. Conclusions: Except for age and histology, the demographic breakdown and epidemiology of HDGC pts with and without CDH1 mutation is similar to other non HDGC high genetic risk pts and similar to pts with sporadic GC. The GC registry will expand to international sites. (Supported by the DeGregorio Family Foundation) [Table: see text] No significant financial relationships to disclose.