title: Evidence of tumor microsatellite instability in gastric cancer with familial aggregation.
abstract: About 90% of gastric cancer (GC) cases appear in a sporadic setting. Nonetheless, in high incidence areas high familial aggregation rates have been recently described. Microsatellite instability (MSI) is thought to be an important molecular phenotype both in sporadic GC and in tumors of the HNPCC spectrum. The aim of this study was to assess the frequency of MSI in GC with familial aggregation. Five quasimonomorphic mononucleotide repeats (BAT-26, BAT-25, NR-24, NR-21 and NR-27) were analyzed in 250 GC patients. Seventy-five patients (30%) had at least one-first-degree family member affected by GC and 63 patients (25.2%) showed MSI. The frequency of MSI was significantly higher in patients with a positive family history of GC (38.7%) compared to patients with other tumor types within the family (15.7%) or with a negative oncological familial history (21.9%, P = 0.004). Within cases with a positive familial oncological history, the MSI frequency in families with GC only was similar to the one observed in families with GC and colon cancer (P = 0.96). Nonetheless, in families with GC and lung cancer, the frequency of MSI was significantly lower (5.6%, P = 0.007). MSI occurs in GCs with familial aggregation. Similar MSI rates have been observed in GC patients with other family members affected by GC or colon cancer. The same does not occur in families with other members affected by lung cancer. Our data seem to suggest that familial aggregation for either GC alone or gastric and colon cancer share common etiological factors in contrast to families with gastric and lung cancers.
authors.affiliation: Department of Human Pathology and Oncology, Unit of Surgical Oncology, University of Siena, Policlinico Le Scotte, 53100 Siena, Italy. pedrazzani@unisi.it
authors.forename: Corrado
authors.initials: C
authors.lastname: Pedrazzani
authors.forename: Giovanni
authors.initials: G
authors.lastname: Corso
authors.forename: Sérgia
authors.initials: S
authors.lastname: Velho
authors.forename: Marina
authors.initials: M
authors.lastname: Leite
authors.forename: Valeria
authors.initials: V
authors.lastname: Pascale
authors.forename: Francesca
authors.initials: F
authors.lastname: Bettarini
authors.forename: Daniele
authors.initials: D
authors.lastname: Marrelli
authors.forename: Raquel
authors.initials: R
authors.lastname: Seruca
authors.forename: Franco
authors.initials: F
authors.lastname: Roviello
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000368:Aged; D003110:Colonic Neoplasms / Q000235:genetics; D005190:Family; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006801:Humans; D008297:Male; D053842:Microsatellite Instability; D008875:Middle Aged; D013274:Stomach Neoplasms / Q000235:genetics* / Q000473:pathology
chemical_list: D048868:Adaptor Proteins, Signal Transducing