title: Molecular and survival differences between familial and sporadic gastric cancers.
abstract: Mismatch repair (MMR) and germline E-cadherin (CDH1) mutations are two of the major pathways of carcinogenesis in familial gastric cancer (GC). A total of 260 sporadic and 66 familial GC patients were enrolled and molecular and survival differences were compared. Familial GC patients had earlier onset and were diagnosed at an earlier stage and had both a better 5-year overall survival rate and 3-year disease-free survival rate compared with sporadic GC patients. Only in diffuse type GC, the MSI-H phenotype and abnormal MMR protein expression were significantly higher in familial GC than in sporadic GC. In MSI-H GC, MLH1 promoter methylation was slightly higher in sporadic GC than familial GC (50% versus 23.1%), while the frequency of MMR gene mutation was slightly higher in familial GC than in sporadic GC (15.4% versus 3.1%). All of the patients with MMR gene mutation had diffuse type GC. Among familial GC patients with CDH1 mutation, most patients (72.3%) had diffuse type GC. In summary, for familial GC patients, we recommend screening of MSI status and CDH1 mutation especially for diffuse type GC. Because of the low incidence, mutation analysis of MMR gene might be considered in MSI-H familial GC with diffuse type only.
authors.affiliation: Division of General Surgery, Department of Surgery, Taipei Veterans General Hospital, 201 Section 2, Shih-Pai Road, Taipei 11217, Taiwan.
authors.forename: Wen-Liang
authors.initials: WL
authors.lastname: Fang
authors.forename: Shih-Ching
authors.initials: SC
authors.lastname: Chang
authors.forename: Yuan-Tzu
authors.initials: YT
authors.lastname: Lan
authors.forename: Kuo-Hung
authors.initials: KH
authors.lastname: Huang
authors.forename: Su-Shun
authors.initials: SS
authors.lastname: Lo
authors.forename: Anna Fen-Yau
authors.initials: AF
authors.lastname: Li
authors.forename: Chin-Wen
authors.initials: CW
authors.lastname: Chi
authors.forename: Chew-Wun
authors.initials: CW
authors.lastname: Wu
authors.forename: Shih-Hwa
authors.initials: SH
authors.lastname: Chiou
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000096:biosynthesis / Q000235:genetics*; D000368:Aged; D015703:Antigens, CD; D015820:Cadherins / Q000096:biosynthesis / Q000235:genetics*; D019175:DNA Methylation / Q000235:genetics; D053843:DNA Mismatch Repair / Q000235:genetics; D018572:Disease-Free Survival; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D053842:Microsatellite Instability; D008875:Middle Aged; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein / Q000235:genetics*; D009687:Nuclear Proteins / Q000096:biosynthesis / Q000235:genetics*; D011401:Promoter Regions, Genetic; D013274:Stomach Neoplasms / Q000453:epidemiology* / Q000235:genetics / Q000473:pathology
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D015703:Antigens, CD; C513384:CDH1 protein, human; D015820:Cadherins; C501486:MLH1 protein, human; D009687:Nuclear Proteins; C497172:MSH2 protein, human; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein
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