Frequency of hereditary non-polyposis colorectal cancer in Danish colorectal cancer patients
- 1Surgical Research Unit 900, Department of Surgery L, Aarhus University Hospital, Aarhus Amtssygehus, Aarhus, Denmark
- 2Department of Clinical Biochemistry, Aarhus University Hospital, Skejby Sygehus, Aarhus, Denmark
- Correspondence to:
Dr N Katballe, Surgical Research Unit, afd. 900, Department of Surgery L, Aarhus Amtssygehus, Aarhus University Hospital, Tage Hansens Gade 2, 8000 Aarhus C, Denmark
- Accepted 12 April 2001
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.
Aim: 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 fulfilment 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.
Conclusion: 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.
- hereditary non-polyposis colorectal cancer
- colorectal cancer
- microsatellite instability
- Danish patients
- CRC, colorectal cancer
- HD, heteroduplex analysis
- hMLH1, mutator L homologue gene (h=human), HNPCC gene
- hMSH2, mutator S homologue gene 2 (h=human) HNPCC gene
- hMSH6, mutator S homologue gene 6 (h=human) HNPCC gene
- HNPCC, hereditary non-polyposis colorectal cancer
- hPMS1–2, human homologue of yeast postmeiotic segregation genes 1 and 2
- ICG-HNPCC, International Collaborative Group for HNPCC
- IHC, immunohistochemistry
- MMR, mismatch repair
- MSI, microsatellite instability
- MSI-H, high microsatellite instability
- MSI-L, low microsatellite instability
- MS-S, stable microsatellites
- PCR, polymerase chain reaction
- SSCP, single stranded conformational polymorphism