title: hMLH1 and hMSH2 gene mutation in Brazilian families with suspected hereditary nonpolyposis colorectal cancer.
abstract: BACKGROUND
  The aim of this study was to search for mutations in the human mutS homolog 2 (hMSH2) and human mutL homolog 1 (hMLH1) genes in 25 unrelated Brazilian kindreds with suspected hereditary nonpolyposis colorectal cancer (HNPCC).
  
  
  METHODS
  The families were grouped according to the following clinical criteria: Amsterdam I or II; familial colorectal cancer (CRC); an early age of onset of CRC in the proband only; or with at least one or two relatives who had HNPCC-related cancers; CRC in the proband only. All patients were studied with direct sequencing.
  
  
  RESULTS
  Ten mutations were detected (10 of 25 [40%]); of nine different mutations, seven were novel. The hMLH1 gene had a higher mutation detection rate than hMSH2 (8 of 25 [32%] vs. 2 of 25 [8%]). Only 3 of these 10 families fulfilled the Amsterdam criteria. Two different polymorphisms were detected in the hMLH1 gene and four in the hMSH2 gene.
  
  
  CONCLUSIONS
  The hMLH1 gene had a higher mutation detection rate than hMSH2. The physician who deals with CRC must take into consideration the heredity issue with patients who present with an early age of onset or a familial history of CRC- or HNPCC-related cancers, including gastric cancer, even if they do not fulfill the former Amsterdam criteria.
authors.affiliation: Department of Pelvic Surgery, the Hospital do Câncer A. C. Camargo, Fundação Antonio Prudente, São Paulo, Brazil.
authors.forename: Benedito Mauro
authors.initials: BM
authors.lastname: Rossi
authors.forename: Ademar
authors.initials: A
authors.lastname: Lopes
authors.forename: Fabio
authors.initials: F
authors.lastname: Oliveira Ferreira
authors.forename: Wilson Toshihiko
authors.initials: WT
authors.lastname: Nakagawa
authors.forename: Cláudia C
authors.initials: CC
authors.lastname: Napoli Ferreira
authors.forename: José C
authors.initials: JC
authors.lastname: Casali Da Rocha
authors.forename: Catarina C
authors.initials: CC
authors.lastname: Simpson
authors.forename: Andrew J G
authors.initials: AJ
authors.lastname: Simpson
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000293:Adolescent; D000328:Adult; D000368:Aged; D001938:Brazil; D002352:Carrier Proteins; D003123:Colorectal Neoplasms, Hereditary Nonpolyposis / Q000235:genetics*; D004268:DNA-Binding Proteins; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein; D009154:Mutation; D009363:Neoplasm Proteins / Q000235:genetics*; D009687:Nuclear Proteins; D010375:Pedigree; D011110:Polymorphism, Genetic; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D017422:Sequence Analysis, DNA
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D004268:DNA-Binding Proteins; C501486:MLH1 protein, human; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; C497172:MSH2 protein, human; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein