title: Frequency of hereditary non-polyposis colorectal cancer in Danish colorectal cancer patients.
abstract: BACKGROUND
  Hereditary non-polyposis colorectal cancer (HNPCC) is an autosomal dominant cancer syndrome, characterised by familial aggregation of HNPCC related cancers, germline mutations in mismatch repair genes, and/or microsatellite instability (MSI) in tumour tissue.
  
  
  OBJECTIVE
  To estimate the frequency of HNPCC among non-selected Danish patients with colorectal cancer (CRC), and to evaluate the value of MSI analysis as a pre-screen test.
  
  
  METHODS
  This was a prospective population based study on consecutive CRC patients. A family history of malignancy was obtained and suspected HNPCC cases were screened for hMLH1/hMSH2 mutations and subjected to MSI analysis. Patients with germline mutations and/or those with Amsterdam criteria I or II families were categorised as HNPCC patients.
  
  
  RESULTS
  Among 1328 eligible CRC patients, 1200 (90.4%) completed a questionnaire. A total of 1.7% (95% confidence interval (CI) 1.0-2.4) (20 cases) were categorised as HNPCC patients. Amsterdam criteria I or II were met in 18 cases (1.5%), and in another two cases (0.2%) pathogenic hMLH1/hMSH2 mutations were detected without fulfillment of the Amsterdam criteria I or II. Among 77 patients younger than 50 years of age, 11 cases (14.3%) were categorised as HNPCC. The Amsterdam criteria I or II were met in eight of 10 gene carriers (80%). The MSI-high phenotype was demonstrated in all 10 gene carriers.
  
  
  CONCLUSIONS
  The frequency of HNPCC was approximately 1.7% among all CRC cases and 14.3% among patients younger than 50 years of age. MSI analysis is a reliable pre-screen test for hMLH1/hMSH2 mutations in families suspected of having HNPCC.
authors.affiliation: Surgical Research Unit 900, Department of Surgery L, Aarhus University Hospital, Aarhus Amtssygehus, Aarhus, Denmark.
authors.forename: N
authors.initials: N
authors.lastname: Katballe
authors.forename: M
authors.initials: M
authors.lastname: Christensen
authors.forename: F P
authors.initials: FP
authors.lastname: Wikman
authors.forename: T F
authors.initials: TF
authors.lastname: Ørntoft
authors.forename: S
authors.initials: S
authors.lastname: Laurberg
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016010:Binomial Distribution; D002352:Carrier Proteins; D003123:Colorectal Neoplasms, Hereditary Nonpolyposis / Q000453:epidemiology* / Q000235:genetics; D016001:Confidence Intervals; D004268:DNA-Binding Proteins; D003718:Denmark / Q000453:epidemiology; D005260:Female; D018095:Germ-Line Mutation; D006579:Heterozygote; D006801:Humans; D015994:Incidence; D008297:Male; D018895:Microsatellite Repeats / Q000235:genetics; D008875:Middle Aged; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein; D009363:Neoplasm Proteins / Q000235:genetics; D009687:Nuclear Proteins; D010375:Pedigree; D010641:Phenotype; D016133:Polymerase Chain Reaction; D011237:Predictive Value of Tests; D011446:Prospective Studies; D011518:Proto-Oncogene Proteins / Q000235:genetics; D012680:Sensitivity and Specificity
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