Familial Cancer

, Volume 4, Issue 3, pp 239–244 | Cite as

Frequency of Familial Colon Cancer and Hereditary Nonpolyposis Colorectal Cancer (Lynch Syndrome) in a Large Population Database

  • Richard A. Kerber
  • Deborah W. Neklason
  • Wade S. Samowitz
  • Randall W. Burt
Article

Abstract

Background and aims: Estimates have been made concerning the fraction of colorectal cancer (CRC) cases that meet Amsterdam I criteria but not Amsterdam II criteria. The aim of this study was to determine in a population setting what fraction of CRC cases can be considered familial high-risk, what fraction of these meet Amsterdam I or II criteria, and what fraction of CRC cases overall meet Amsterdam I and II criteria. Methods: The Utah Population Data Base (UPDB), which links Utah genealogies to the Utah Cancer Registry, was used to examine the aims of the study. Familial high-risk was operationally defined as CRC occurring at an age <50 years or as a part of a first-degree relative pair. A subset of Amsterdam positive cancers was tested for microsatellite instability (MSI) to determine what fraction of Amsterdam families was likely to have hereditary nonpolyposis colorectal cancer (HNPCC). Results: Of the 6,628 CRC cases in the UPDB, 24.5% met the criteria for familial high-risk. Of these, 2.6% met Amsterdam I criteria and 5.5% Amsterdam II. Of total data base CRC cases, 0.8% met Amsterdam I criteria and 2.3% Amsterdam II. In a subset of colon tumors from Amsterdam families, 70% were MSI stable. Conclusions: Although nearly 25% of CRC cases in our population data base met a simple definition of familial high-risk, only a small fraction of these and a smaller fraction of total CRC cases met Amsterdam I or II criteria. Less than half of a limited set of tumors from Amsterdam families were MSI positive.

Key words

Amsterdam criteria familial colon cancer hereditary nonpolyposis colorectal cancer HNPCC Lynch syndrome 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Burt, RW 2000Colon cancer screeningGastroenterology11983753CrossRefPubMedGoogle Scholar
  2. 2.
    Cannon-Albright, LA,  et al. 1988Common inheritance of susceptibility to colonic adenomatous polyps and associated colorectal cancersN Engl J Med3195337PubMedGoogle Scholar
  3. 3.
    Lichtenstein, P,  et al. 2000Environmental and heritable factors in the causation of cancerN Engl J Med3437885CrossRefPubMedGoogle Scholar
  4. 4.
    Potter, JD 1999Colorectal cancer: molecules and populationsJ Natl Cancer Inst9191632CrossRefPubMedGoogle Scholar
  5. 5.
    Johns, LE, Houlston, RS 2001A systematic review and meta-analysis of familial colorectal cancer riskAm J Gastroenterol9629923003CrossRefPubMedGoogle Scholar
  6. 6.
    Winawer, S,  et al. 2003Colorectal cancer screening and surveillance: Clinical guidelines and rationale-Update based on new evidenceGastroenterology12454460CrossRefPubMedGoogle Scholar
  7. 7.
    Samowitz, WS,  et al. 2001The colon cancer burden of genetically defined hereditary nonpolyposis colon cancerGastroenterology1218308CrossRefPubMedGoogle Scholar
  8. 8.
    Lynch, HT, Chapelle de la, A 2003Hereditary colorectal cancerN Engl J Med34891932CrossRefPubMedGoogle Scholar
  9. 9.
    Lewis, C, Neuhausen, SL, Daley, D et al 1996Genetic heterogeneity and unmapped genes for colorectal cancerCancer Res56138288PubMedGoogle Scholar
  10. 10.
    Vasen, HFA,  et al. 1999New clinical criteria for hereditary nonpolyposis colorectal cancer (HNPCC, Lynch syndrome) proposed by the International Collaborative Group on HNPCCGastroenterology116145356PubMedGoogle Scholar
  11. 11.
    Skolnick, M 1980

    The Utah Genealogical Database: A resource for genetic epidemiology

    Cairns, JJLyon, JLSkolnick, M eds. Cancer Incidence in Defined Populations.Cold Spring Harbor LaboratoryCold Spring Harbor, NY28596
    Google Scholar
  12. 12.
    Wylie, JE, Mineau, GP 2003Biomedical databases: Protecting privacy and promoting researchTrends Biotechnol211136CrossRefPubMedGoogle Scholar
  13. 13.
    Vasen, HFA,  et al. 1991The International Collaborative Group on Hereditary Non-Polyposis Colorectal Cancer (ICG-HNPCC)Dis Colon Rectum344245CrossRefPubMedGoogle Scholar
  14. 14.
    Umar, A,  et al. 2004Revised Bethesda guidelines for hereditary nonpolyposis colorectal cancer (Lynch syndrome) and microsatellite instabilityJ Natl Cancer Inst962618PubMedGoogle Scholar
  15. 15.
    Samowitz, WS, Slattery, ML, Kerber, RA 1995Microsatellite instability in human colonic cancer is not a useful clinical indicator of familial colorectal cancerGastroenterology109176571CrossRefPubMedGoogle Scholar
  16. 16.
    Boland, CR,  et al. 1998A National Cancer Institute Workshop on microsatellite instability for cancer detection and familial predisposition: Development of international criteria for the determination of microsatellite instability in colorectal cancerCancer Res58524857PubMedGoogle Scholar
  17. 17.
    Spirio, L,  et al. 1993Alleles of the APC gene: An attenuated form of familial polyposisCell759517CrossRefPubMedGoogle Scholar
  18. 18.
    Burt, RW,  et al. 2004Genetic testing and phenotype in a large kindred with attenuated familial adenomatous polyposisGastroenterology12744451CrossRefPubMedGoogle Scholar
  19. 19.
    Solomon CH, Pho LN, Burt RW. Current status of genetic testing for colorectal cancer susceptibility. Oncology (Huntingt), 2002; 16(2): 161–71; discussion 176, 179–80Google Scholar
  20. 20.
    O’Brien, E,  et al. 1994Genetic structure of the Utah Mormons: Comparison of results based on RFLPs, blood groups, migration matrices, isonymy, and pedigreesHum Biol6674359PubMedGoogle Scholar
  21. 21.
    McLellan, T, Jorde, LB, Skolnick, MH 1984Genetic distances between the Utah Mormons and related populationsAm J Hum Genet3683657PubMedGoogle Scholar
  22. 22.
    Jorde, LB 1982The genetic structure of the Utah Mormons: Migration analysisHum Biol5458397PubMedGoogle Scholar

Copyright information

© Springer 2005

Authors and Affiliations

  • Richard A. Kerber
    • 1
  • Deborah W. Neklason
    • 1
  • Wade S. Samowitz
    • 2
  • Randall W. Burt
    • 3
    • 4
  1. 1.Department of Oncological SciencesUniversity of Utah, School of MedicineUSA
  2. 2.Department of PathologyUniversity of Utah, School of MedicineUSA
  3. 3.Department of MedicineUniversity of Utah, School of MedicineUSA
  4. 4.Huntsman Cancer InstituteUniversity of UtahSalt Lake CityUSA

Personalised recommendations