title: CDH1/E-cadherin germline mutations in early-onset gastric cancer.
abstract: BACKGROUND
  Gastric cancer remains a leading cause of cancer deaths worldwide. Genetic factors, including germline mutations in E-cadherin (CDH1, MIM#192090) in hereditary diffuse gastric cancer (HDGC, MIM#137215), are implicated in this disease. Family studies have reported CDH1 germline mutations in HDGC but the role of CDH1 germline mutations in the general population remains unclear.
  
  
  OBJECTIVE
  To examine the frequency of CDH1 germline mutations in a population-based series of early-onset gastric cancer (EOGC <50 years old).
  
  
  METHODS
  211 cases of EOGC were identified in Central-East Ontario region from 1989 to 1993, with archival material and histological confirmation of non-intestinal type gastric cancer available for 81 subjects. Eligible cases were analysed for CDH1 germline mutations by single-strand conformation polymorphism, variants were sequenced, and tumours from cases with functional mutations were stained for E-cadherin (HECD-1) using immunohistochemistry.
  
  
  RESULTS
  1155 (89%) of 1296 polymerase chain reactions amplified successfully. One new germline deletion (nt41delT) was identified in a 30-year-old patient with isolated cell gastric cancer. The overall frequency of germline CDH1 mutations was 1.3% (1/81) for EOGC and 2.8% (1/36) for early-onset isolated cell gastric cancer.
  
  
  CONCLUSIONS
  This is the first population-based study, in a low-incidence region, of genetic predisposition to gastric cancer. Combined with our previous report of germline hMLH1 mutations in two other subjects from this series, it is suggested that 2-3% of EOCG cases in North Americans may be owing to high-risk genetic mutations. These data should inform cancer geneticists on the utility of searching for specific genetic mutations in EOGC.
authors.forename: J T
authors.initials: JT
authors.lastname: Bacani
authors.forename: M
authors.initials: M
authors.lastname: Soares
authors.forename: R
authors.initials: R
authors.lastname: Zwingerman
authors.forename: N
authors.initials: N
authors.lastname: di Nicola
authors.forename: J
authors.initials: J
authors.lastname: Senz
authors.forename: R
authors.initials: R
authors.lastname: Riddell
authors.forename: D G
authors.initials: DG
authors.lastname: Huntsman
authors.forename: S
authors.initials: S
authors.lastname: Gallinger
mesh_terms: D000328:Adult; D017668:Age of Onset; D015703:Antigens, CD; D015820:Cadherins / Q000235:genetics*; D004252:DNA Mutational Analysis; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing; D018095:Germ-Line Mutation; D006801:Humans; D013274:Stomach Neoplasms / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology
chemical_list: D015703:Antigens, CD; C513384:CDH1 protein, human; D015820:Cadherins