title: Frequency of hereditary non-polyposis colorectal cancer among unselected patients with colorectal cancer in Germany.
abstract: BACKGROUND
  Hereditary non-polyposis colorectal cancer (HNPCC) is a major form of familial colorectal cancer (CRC). It is diagnosed when either the Amsterdam criteria (AC) are fulfilled or mutations in one of the mismatch repair (MMR) genes have been identified. This project aims at estimating the proportion of HNPCC among unselected patients with CRC.
  
  
  METHODS
  During a period of 2 years, a total of 351 non-selected patients with CRC were registered prospectively. 92 patients met the Bethesda criteria (9 of them fulfilled the AC) and 259 did not. 348 tumours were examined for microsatellite instability (MSI) and expression of MMR proteins.
  
  
  RESULTS
  MSI-H and MSI-L were identified in 17 and 6%, respectively. Loss of MSH2 or MLH1 was found in 1.5 and 8.8%, respectively. Based on the results of tumour tissue analyses, 80 patients with MSI and/or loss of MSH2 or MLH1 expression were identified as candidates for germline mutation screening. DNA of 40/80 patients was available. These patients were screened for MSH2 and MLH1 mutations; 19/40 patients with MSI and normal MSH2 or MLH1 expression were screened for mutations in MSH6. Three patients had relevant MMR gene mutations and six variants of unknown functional relevance were detected.
  
  
  CONCLUSIONS
  After adjusting for the cases not evaluable for germline mutations, 1.7% of the CRC patients had HNPCC proven by molecular genetics.
authors.affiliation: Department of Internal Medicine I,University of Bonn, Bonn, Germany. christof.lamberti@ukb.uni-bonn.de
authors.forename: C
authors.initials: C
authors.lastname: Lamberti
authors.forename: E
authors.initials: E
authors.lastname: Mangold
authors.forename: C
authors.initials: C
authors.lastname: Pagenstecher
authors.forename: M
authors.initials: M
authors.lastname: Jungck
authors.forename: D
authors.initials: D
authors.lastname: Schwering
authors.forename: M
authors.initials: M
authors.lastname: Bollmann
authors.forename: J
authors.initials: J
authors.lastname: Vogel
authors.forename: D
authors.initials: D
authors.lastname: Kindermann
authors.forename: R
authors.initials: R
authors.lastname: Nikorowitsch
authors.forename: N
authors.initials: N
authors.lastname: Friedrichs
authors.forename: B
authors.initials: B
authors.lastname: Schneider
authors.forename: F
authors.initials: F
authors.lastname: Houshdaran
authors.forename: I G H
authors.initials: IG
authors.lastname: Schmidt-Wolf
authors.forename: W
authors.initials: W
authors.lastname: Friedl
authors.forename: P
authors.initials: P
authors.lastname: Propping
authors.forename: T
authors.initials: T
authors.lastname: Sauerbruch
authors.forename: R
authors.initials: R
authors.lastname: Büttner
authors.forename: M
authors.initials: M
authors.lastname: Mathiak
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins / Q000235:genetics; D015331:Cohort Studies; D003123:Colorectal Neoplasms, Hereditary Nonpolyposis / Q000453:epidemiology* / Q000235:genetics*; D004260:DNA Repair; D004268:DNA-Binding Proteins / Q000235:genetics; D018095:Germ-Line Mutation; D005858:Germany / Q000453:epidemiology; D006801:Humans; D053842:Microsatellite Instability; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein / Q000235:genetics; D009687:Nuclear Proteins / Q000235:genetics; D011446:Prospective Studies
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