title: Clinicopathological and genetic features of Chinese hereditary nonpolyposis colorectal cancer (HNPCC).
abstract: The aim of this study was to investigate the clinical value of different criteria and to understand the relationship between genotype and phenotype in Chinese hereditary nonpolyposis colorectal cancer (HNPCC). A total of 116 unrelated probands of suspected HNPCC families from the Fudan Colorectal Registry were studied. A total of 32, 28, and 56 families fulfilled the Amsterdam criteria, the Fudan criteria and the revised Bethesda guideline, respectively. Direct DNA sequencing of all exons of hMSH2 and hMLH1 genes were performed on all 116 samples. Mutations and clinicopathological features were compared between the groups. Thirty-two pathological germline mutations were identified. Out of 32 mutations, 16 were located at hMLH1 and 16 at hMSH2. The sensitivity of Amsterdam criteria was 50%, specificity was 81%, and Youden's index was 31%. The sensitivity of Fudan criteria was 75%, specificity was 58%, and Youden's index was 33%. Among all the 32 families with mutations, families with hMSH2 mutation had a higher ratio of synchronous and metachronous colon cancers than families with hMLH1 mutation (33 vs. 6%, P=0.04). Patients with hMSH2 mutation more frequently harbour synchronous and metachronous colon cancers. Fudan criteria had a little higher sensitivity and accuracy than Amsterdam criteria for identification of Chinese HNPCC.
authors.affiliation: Department of Colorectal Surgery, Fudan University Shanghai Cancer Center, Shanghai, 200032, China.
authors.forename: Fangqi
authors.initials: F
authors.lastname: Liu
authors.forename: Li
authors.initials: L
authors.lastname: Yang
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Zhou
authors.forename: Weiqi
authors.initials: W
authors.lastname: Sheng
authors.forename: Sanjun
authors.initials: S
authors.lastname: Cai
authors.forename: Lei
authors.initials: L
authors.lastname: Liu
authors.forename: Peng
authors.initials: P
authors.lastname: Nan
authors.forename: Ye
authors.initials: Y
authors.lastname: Xu
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics*; D044466:Asian People / Q000235:genetics; D002681:China / Q000453:epidemiology; D003123:Colorectal Neoplasms, Hereditary Nonpolyposis / Q000235:genetics* / Q000473:pathology; D004252:DNA Mutational Analysis; D005260:Female; D056726:Genetic Association Studies; D018095:Germ-Line Mutation; D006801:Humans; D008297:Male; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein / Q000235:genetics*; D009687:Nuclear Proteins / Q000235:genetics*; D012042:Registries
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C501486:MLH1 protein, human; D009687:Nuclear Proteins; C497172:MSH2 protein, human; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein