title: Nationwide study of clinical and molecular features of hereditary non-polyposis colorectal cancer (HNPCC) in Latvia.
abstract: BACKGROUND
  The mutational spectrum of mismatch repair (MMR) genes in the Baltic States has been reported to be quite similar to that in Poland; however during a country-wide study considerable differences in the population of Latvia were discovered. This study was undertaken to investigate the clinical and molecular features of HNPCC in Latvia.
  
  
  METHODS
  Family cancer histories were collected, from January 2000 until October 2003, for 702 consecutive hospital based colorectal cancer (CRC) cases. In families suspected of having a history consistent with hereditary non-polyposis colorectal cancer (HNPCC), DNA testing for MLH1, MSH2 and MSH6 genes was performed. Immunohistochemical examination of the normal and the cancer tissue from large bowel tumors was undertaken for MSH2 and MSH6 protein expression in 182 out of 702 (26%) of the cases.
  
  
  RESULTS
  Among the 702 CRC patients only 1 (0.14%) fulfilled the Amsterdam criteria. Thirteen (1.9%) cases matched the criteria for suspected HNPCC and 10 (1.4%) cases matched the late onset HNPCC criteria. Altogether in 7 out of 702 (1%) cases MMR gene mutations were detected: 2 in MLH1, 3 in MSH2 and 2 in MSH6 gene. Only one out of the seven mutations was registered in the Human Genome Mutation Database and the ICG (International Collaborational Group)-HNPCC mutation data base. Negative MSH2 and MSH6 protein expression was detected in 4 (2.2%) and 18 out of 182 (9.9%) cases respectively.
  
  
  CONCLUSIONS
  The role of the classical Amsterdam criteria in diagnosing HNPCC in CRC patients from Latvia is very limited and diagnostic criteria for suspected HNPCC are the most effective. The frequency of constitutional mutations within the MMR genes is 1% of all newly diagnosed CRC cases and the spectrum of mutations is potentially characteristic.
authors.affiliation: Hereditary Cancer Institute, Riga Stradins University, Riga, Latvia. hci@stradini.lv
authors.forename: Arvids
authors.initials: A
authors.lastname: Irmejs
authors.forename: Viktors
authors.initials: V
authors.lastname: Borosenko
authors.forename: Inga
authors.initials: I
authors.lastname: Melbarde-Gorkusa
authors.forename: Andris
authors.initials: A
authors.lastname: Gardovskis
authors.forename: Marianna
authors.initials: M
authors.lastname: Bitina
authors.forename: Grzegorz
authors.initials: G
authors.lastname: Kurzawski
authors.forename: Janina
authors.initials: J
authors.lastname: Suchy
authors.forename: Bohdan
authors.initials: B
authors.lastname: Gorski
authors.forename: Janis
authors.initials: J
authors.lastname: Gardovskis
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins / Q000235:genetics; D003123:Colorectal Neoplasms, Hereditary Nonpolyposis / Q000453:epidemiology / Q000235:genetics*; D053843:DNA Mismatch Repair; D004252:DNA Mutational Analysis; D004268:DNA-Binding Proteins / Q000235:genetics; D005192:Family Health; D005260:Female; D006801:Humans; D007844:Latvia / Q000453:epidemiology; D008297:Male; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein / Q000235:genetics; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics; D010375:Pedigree
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D004268:DNA-Binding Proteins; C094443:G-T mismatch-binding protein; C501486:MLH1 protein, human; D009687:Nuclear Proteins; C497172:MSH2 protein, human; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein