Nationwide study of clinical and molecular features of hereditary non-polyposis colorectal cancer (HNPCC) in Latvia.
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.
Irmejs
Arvids
A
Hereditary Cancer Institute, Riga Stradins University, Riga, Latvia. hci@stradini.lv
Borosenko
Viktors
V
Melbarde-Gorkusa
Inga
I
Gardovskis
Andris
A
Bitina
Marianna
M
Kurzawski
Grzegorz
G
Suchy
Janina
J
Gorski
Bohdan
B
Gardovskis
Janis
J
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
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