title: High incidence of familial gastric cancer in Tuscany, a region in Italy.
abstract: OBJECTIVE
  Only 1% of diffuse gastric cancers occur in families with autosomal dominant gastric cancer susceptibility. Germline mutations in the E-cadherin gene account for the hereditary diffuse gastric cancer (HDGC) syndrome. We studied a large cohort of gastric cancer patients from Tuscany, a region in Italy, to evaluate the presence of familial clustering of gastric cancer.
  
  
  METHODS
  238 pedigrees were retrospectively studied by structured interviews. All probands with diagnosed gastric cancer were contacted in-person or by phone and tumor types were assessed in first- and second-degree relatives. Familial aggregation was investigated in order to search for families with suspected HDGC.
  
  
  RESULTS
  Familial aggregation for gastric cancer was observed in 79 of 238 cases (33.2%). Among these, there were 64 families (81%) with one gastric cancer other than the proband, 10 families with two gastric cancers (12.7%) and 5 families with three gastric cancers (6.3%). Fourteen families fulfilled the HDGC clinical criteria, one of them presenting with a pathogenic germline mutation in the E-cadherin gene (7.1%).
  
  
  CONCLUSIONS
  The prevalence of familial HDGC appears extremely high. Since only one pathogenic germline mutation was noted in a family fulfilling the HDGC clinical criteria, factors other than E-cadherin gene mutations may contribute to the familial clustering of HDGC.
authors.affiliation: Department of Human Pathology and Oncology, University of Siena, Siena, Italy. roviello@unisi.it
authors.forename: Franco
authors.initials: F
authors.lastname: Roviello
authors.forename: Giovanni
authors.initials: G
authors.lastname: Corso
authors.forename: Corrado
authors.initials: C
authors.lastname: Pedrazzani
authors.forename: Daniele
authors.initials: D
authors.lastname: Marrelli
authors.forename: Giulia
authors.initials: G
authors.lastname: De Falco
authors.forename: Gianpaolo
authors.initials: G
authors.lastname: Suriano
authors.forename: Carla
authors.initials: C
authors.lastname: Vindigni
authors.forename: Anna
authors.initials: A
authors.lastname: Berardi
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Garosi
authors.forename: Alfonso
authors.initials: A
authors.lastname: De Stefano
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Leoncini
authors.forename: Raquel
authors.initials: R
authors.lastname: Seruca
authors.forename: Enrico
authors.initials: E
authors.lastname: Pinto
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015820:Cadherins / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease; D018095:Germ-Line Mutation; D006801:Humans; D015994:Incidence; D007558:Italy / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D010375:Pedigree; D012189:Retrospective Studies; D013274:Stomach Neoplasms / Q000453:epidemiology* / Q000235:genetics*
chemical_list: D015820:Cadherins