title: Clinical and genetic characteristics of Chinese hereditary nonpolyposis colorectal cancer families.
abstract: OBJECTIVE
  To analyze the clinical characteristics of Chinese hereditary nonpolyposis colorectal cancer (HNPCC) families and to screen the germline mutations of human mismatch repair genes hMLH1 and hMSH2 in the probands.
  
  
  METHODS
  Thirty-one independent Chinese HNPCC families were collected in Zhejiang Province. All of them met Chinese HNPCC criteria. Clinical data about patient gender, site of colorectal cancer, age of onset, history of multiple colorectal cancer, associated extracolonic cancer were recorded. PCR and denaturing high performance liquid chromatography (DHPLC) were employed to screen the mutations. Sequencing analysis was used to find out the exact mutation site and characteristics of the samples showing abnormal DHPLC profiles.
  
  
  RESULTS
  One hundred and thirty-six malignant neoplasms were found in 107 patients including 14 multiple cancers. One hundred and six of the 136 neoplasms (77.9%) were diagnosed as colorectal cancer, with an average age of onset at 48.57 +/- 29.00 years. Gastric cancer was the most common extracolonic cancer (10.3%) in these families. Twenty-three different sequence variations in hMLHl and hMSH2 genes were detected in these 17 families. Fifteen sequence variations were located in the exons, including 5 SNPs, 3 silent mutations, 3 missense mutations, 2 nonsense mutations and 2 frameshift mutations. The latter seven mutations seemed to be pathogenic.
  
  
  CONCLUSIONS
  Germline mutations of hMLH1 and hMSH2 genes are identified in about one-third HNPCC kindreds fulfilling Chinese HNPCC criteria. Chinese HNPCC families have some particular clinical characteristics, such as a left-sided predominance, less synchronous or metachronous colorectal cancer, and frequent occurrence of gastric cancer.
authors.affiliation: Cancer Institute, the 2nd Affiliated Hospital, College of Medicine, Zhejiang University, 88 Jie-Fang Road, Hangzhou 310009, Zhejiang Province, China.
authors.forename: Xu-Lin
authors.initials: XL
authors.lastname: Wang
authors.forename: Ying
authors.initials: Y
authors.lastname: Yuan
authors.forename: Su-Zhan
authors.initials: SZ
authors.lastname: Zhang
authors.forename: Shan-Rong
authors.initials: SR
authors.lastname: Cai
authors.forename: Yan-Qin
authors.initials: YQ
authors.lastname: Huang
authors.forename: Qiang
authors.initials: Q
authors.lastname: Jiang
authors.forename: Shu
authors.initials: S
authors.lastname: Zheng
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000328:Adult; D000368:Aged; D002352:Carrier Proteins / Q000235:genetics*; D002681:China / Q000453:epidemiology; D002851:Chromatography, High Pressure Liquid; D003123:Colorectal Neoplasms, Hereditary Nonpolyposis / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology; D005260:Female; D052138:Genes, Neoplasm; D020022:Genetic Predisposition to Disease / Q000453:epidemiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein / Q000235:genetics*; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics*; D017422:Sequence Analysis, DNA; D013274:Stomach Neoplasms / Q000453:epidemiology / Q000235:genetics
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; C501486:MLH1 protein, human; D009687:Nuclear Proteins; C497172:MSH2 protein, human; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein