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Familial Adenomatous Polyposis and Turcot and Peutz-Jeghers Syndromes

  • Holly L. Neibergs
  • Amy T. Massey
Chapter
  • 1.7k Downloads

Abstract

Familial adenomatous polyposis (FAP) is an autosomal dominantly inherited disorder that predisposes affected individuals to colon cancer through the early development of hundreds to thousands of adenomatous polyps (Figure 18-1). Florid polyposis throughout the colon will develop in 50% of affected individuals by age 16, and 95% will have polyposis by age 35.1 If left untreated, colorectal cancer is inevitable in those with FAP, with an average age at diagnosis of 39 years. The incidence of FAP is estimated to be 1 in 8,300 to 1 in 14,025 live births and represents less than 1% of all colon cancers.1 FAP is clinically diagnosed when an individual has greater than 100 colorectal adenomatous polyps.

Keywords

Familial Adenomatous Polyposis Adenomatous Polyp Desmoid Tumor Mismatch Repair Gene Familial Adenomatous Polyposis Patient 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. 1.
    American Gastroenterological Association. AGA technical review on hereditary colorectal cancer and genetic testing. Gastroenterology. 2001;121:198–213.CrossRefGoogle Scholar
  2. 2.
    Soravia C, Berk T, Madlensky L, et al. Genotype-phenotype correlations in attenuated adenomatous polyposis coli. Am J Hum Genet. 1998;62:1290–1301.PubMedCrossRefGoogle Scholar
  3. 3.
    Lynch HT, Smyrk TC, Watson P, et al. Hereditary flat adenoma syndrome: a variant of familial adenomatous polyposis? Dis Colon Rectum. 1992;35:411–421.PubMedCrossRefGoogle Scholar
  4. 4.
    Spirio L, Olschwang S, Groden J, et al. Alleles of the APC gene: an attenuated form of familial polyposis. Cell. 1993;75:951–957.PubMedCrossRefGoogle Scholar
  5. 5.
    Kinzler KW, Vogelstein B. Colorectal tumors. In: Vogelstein B, Kinzler KW, eds. The Genetic Basis of Human Cancer. New York: McGraw-Hill; 2002:583–612.Google Scholar
  6. 6.
    Truta B, Allen BA, Conrad PG, et al. A comparison of the phenotype and genotype in adenomatous polyposis patients with and without a family history. Fam Cancer. 2005;4:127–133.PubMedCrossRefGoogle Scholar
  7. 7.
    Moisio A-L, Jarvinen H, Peltomaki P. Genetic and clinical characterisation of familial adenomatous polyposis: a population based study. Gut. 2002;50:845–850.PubMedCrossRefGoogle Scholar
  8. 8.
    Friedl W, Caspari R, Sengteller M, et al. Can APC mutation analysis contribute to therapeutic decisions in familial adenomatous polyposis? Experience from 680 FAP families. Gut. 2001;48:515–521.PubMedCrossRefGoogle Scholar
  9. 9.
    Heppner Goss K, Trzepacz C, Tuohy TM, Groden J. Attenuated APC alleles produce functional protein from internal translation initiation. Proc Natl Acad Sci USA. 2002;99:8161–8166.PubMedCrossRefGoogle Scholar
  10. 10.
    Sieber OM, Lipton L, Crabtree M, et al. Multiple colorectal adenomas, classic adenomatous polyposis, and germ-line mutations in MYH. N Engl J Med. 2003;348:791–799.PubMedCrossRefGoogle Scholar
  11. 11.
    Hedge MR, Chong B, Blazo ME, et al. A homozygous mutation in MSH6 causes Turcot syndrome. Clin Cancer Res. 2005;11:4689–4693.CrossRefGoogle Scholar
  12. 12.
    Hamilton SR, Liu B, Parsons RE, et al. The molecular basis of Turcot’s syndrome. N Engl J Med. 1995;332:839–847.PubMedCrossRefGoogle Scholar
  13. 13.
    Wallis YL, Morton DG, McKeown CM, Macdonald F. Molecular analysis of the APC gene in 205 families: extended genotype-phenotype correlation in FAP and evidence of the role of APC amino acid changes in colorectal cancer predisposition. J Med Genet. 1999;36:14–20.PubMedGoogle Scholar
  14. 14.
    Leung SY, Yuen ST, Chan TL, et al. Chromosomal instability and p53 inactivation are required for genesis of glioblastoma but not for colorectal cancer in patients with germline mismatch repair gene mutation. Oncogene. 2000;19:4079–4083.PubMedCrossRefGoogle Scholar
  15. 15.
    Miyaki M, Iijima T, Shiba K, et al. Alterations of repeated sequences in 5′ upstream and coding regions in colorectal tumors from patients with hereditary nonpolyposis colorectal cancer and Turcot syndrome. Oncogene. 2001;20:5215–5218.PubMedCrossRefGoogle Scholar
  16. 16.
    Boardman LA. Heritable colorectal cancer syndromes: recognition and preventive management. Gastroenterol Clin North Am. 2002;31:1107–1131.PubMedCrossRefGoogle Scholar
  17. 17.
    Aaltonen L. Peutz-Jeghers syndrome. In: Vogelstein B, Kinzler KW, eds. The Genetic Basis of Human Cancer. New York: McGraw-Hill; 2002:337–341.Google Scholar
  18. 18.
    Hampel H, Peltomaki P. Hereditary colorectal cancer: risk assessment and management. Clin Genet. 2000;58:89–97.PubMedCrossRefGoogle Scholar
  19. 19.
    Giardiello FM, Brensinger JD, Tersmette AC, et al. Very high risk of cancer in familial Peutz-Jeghers syndrome. Gastroenterology. 2000;119:1447–1453.PubMedCrossRefGoogle Scholar
  20. 20.
    Ylikorkala A, Avizienyte E, Tomlinson IP, et al. Mutations and impaired function of LKB1 in familial and non-familial Peutz-Jeghers syndrome and a sporadic testicular cancer. Hum Mol Genet. 1999;8:45–51.PubMedCrossRefGoogle Scholar
  21. 21.
    Karuman P, Gozani O, Odze RD, et al. The Peutz-Jegher gene product LKB1 is a mediator of p53-dependent cell death. Mol Cell. 2001;7:1307–1319.PubMedCrossRefGoogle Scholar
  22. 22.
    Mehenni H, Lin-Marq N, Buchet-Poyau K, et al. LKB1 interacts with and phosphorylates PTEN: a functional link between two proteins involved in cancer predisposing syndromes. Hum Mol Genet. 2005;14:2209–2219.PubMedCrossRefGoogle Scholar
  23. 23.
    Forcet C, Etienne-Manneville S, Gaude H, et al. Functional analysis of Peutz-Jeghers mutations reveals that the LKB1 C-terminal region exerts a crucial role in regulating both the AMPK pathway and the cell polarity. Hum Mol Genet. 2005;14:1283–1292.PubMedCrossRefGoogle Scholar
  24. 24.
    Gruber SB, Entius MM, Petersen GM, et al. Pathogenesis of adenocarcinoma in Peutz-Jeghers syndrome. Cancer Res. 1998;58:5267–5270.PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2007

Authors and Affiliations

  • Holly L. Neibergs
    • 1
  • Amy T. Massey
    • 2
  1. 1.Hereditary Cancer InstituteNorton HealthcareLouisvilleUSA
  2. 2.Department of Biochemistry and Molecular BiologyUniversity of Louisville School of MedicineLouisvilleUSA

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