title: History, pathogenesis, and management of familial gastric cancer: original study of John XXIII's family.
abstract: BACKGROUND
  Hereditary diffuse gastric cancer is associated with the E-cadherin germline mutations, but genetic determinants have not been identified for familial intestinal gastric carcinoma. The guidelines for hereditary diffuse gastric cancer are clearly established; however, there are no defined recommendations for the management of familial intestinal gastric carcinoma.
  
  
  METHODS
  In this study we describe Pope John XXIII's pedigree that harboured gastric cancer as well as six other family members. Family history was analysed according to the International Gastric Cancer Linkage Consortium criteria, and gastric tumours were classified in accord with the last Japanese guidelines.
  
  
  RESULTS
  Seven out of 109 members in this pedigree harboured gastric cancer, affecting two consecutive generations. John XXIII's clinical tumour (cTN) was classified as cT4bN3a (IV stage). In two other cases, gastric carcinomas were classified as intestinal histotype and staged as pT1bN0 and pT2N2, respectively.
  
  
  CONCLUSIONS
  Pope John XXIII's family presents a strong aggregation for gastric cancer affecting almost seven members; it spreads through two consecutive generations. In absence of defined genetic causes and considering the increased risk of gastric cancer's development in these families, as well as the high mortality rates and advanced stages, we propose an intensive surveillance protocol for asymptomatic members.
authors.affiliation: Department of Human Pathology and Oncology, Section of General Surgery and Surgical Oncology and Translational Research Laboratory, University of Siena, Viale Bracci, 53100 Siena, Italy. corso.giov@tiscali.it
authors.forename: Giovanni
authors.initials: G
authors.lastname: Corso
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Roncalli
authors.forename: Daniele
authors.initials: D
authors.lastname: Marrelli
authors.forename: Fátima
authors.initials: F
authors.lastname: Carneiro
authors.forename: Franco
authors.initials: F
authors.lastname: Roviello
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D005190:Family; D005260:Female; D030342:Genetic Diseases, Inborn / Q000235:genetics / Q000473:pathology / Q000628:therapy; D006239:Haplotypes; D006801:Humans; D008297:Male; D010375:Pedigree; D013274:Stomach Neoplasms / Q000235:genetics / Q000473:pathology / Q000628:therapy