Familial Adenomatous Polyposis and Turcot and Peutz–Jeghers Syndromes

Chapter

Abstract

To date the majority of colorectal cancers are thought to be sporadic. However, familial predisposition has been well recognized for years. Familial adenomatous polyposis coli, Turcot syndrome, Gardner syndrome, and Peutz–Jeghers syndrome are examples of hereditary syndromes that predispose individuals to colorectal adenocarcinoma as well as a host of other malignant, hamartomatous, and benign growths. While not comprehensive of all familial colorectal predisposition syndromes, a summary of these syndromes is provided in this chapter.

Keywords

Familial adenomatous polyposis coli FAP APC Turcot syndrome Gardner syndrome Attenuated polyposis Desmoid tumors Epidermoid cyst Duodenal adenocarcinoma Papillary thyroid carcinoma CNS tumors Hepatoblastoma CHRPE Peutz-Jeghers syndrome STK11 Juvenile polyposis Intussusception Peutz-Jeghers polyps Mucocutaneous pigmentation 
This is a preview of subscription content, log in to check access.

References

  1. 1.
    Bulow S, Faurschou Nielsen T, Bulow C, Bisgaard ML, Karlsen L, Moesgaard F. The incidence rate of familial adenomatous polyposis. Results from the Danish Polyposis Register. Int J Colorectal Dis. 1996;11:88–91.CrossRefPubMedGoogle Scholar
  2. 2.
    Jarvinen HJ. Epidemiology of familial adenomatous polyposis in Finland: impact of family screening on colorectal cancer rate and survival. Gut. 1992;1992(33):357–60.CrossRefGoogle Scholar
  3. 3.
    American Gastroenterology Association. AGA technical review on hereditary colorectal cacner and genetic testing. Gastroenterology. 2001;121:198–213.CrossRefGoogle Scholar
  4. 4.
    Gardner EJ. A genetic and clinical study of intestinal polyposis, a predisposing factor for carcinoma of the colon and rectum. Am J Hum Genet. 1951;3:167–76.PubMedCentralPubMedGoogle Scholar
  5. 5.
    Turcot J, Despres JP, St Pierre F. Malignant tumors of the central nervous system associated with familial polyposis of the colon: report of two cases. Dis Colon Rectum. 1959;2:465–8.CrossRefPubMedGoogle Scholar
  6. 6.
    Kinzler KW, Nilbert MC, Su LK, Vogelstein B, Bryan TM, Levy DB, et al. Identification of FAP locus genes from chromosome 5q21. Science. 1991;253:661–5.CrossRefPubMedGoogle Scholar
  7. 7.
    Jarrar AM, Milas M, Mitchell J, Laguardia L, O'Malley M, Berber E, et al. Screening for thyroid cancer in patients with familial adenomatous polyposis. Ann Surg. 2011;253:515–21. doi: 10.1097/SLA.0b013e3181fcba8a.CrossRefPubMedGoogle Scholar
  8. 8.
    Harach HR, Williams GT, Williams ED. Familial adenomatous polyposis associated thyroid carcinoma: a distinct type of follicular cell neoplasm. Histopathology. 1994;25:549–61.CrossRefPubMedGoogle Scholar
  9. 9.
    Nose V. Thyroid cancer of follicular cell origin in inherited tumor syndromes. Adv Anat Pathol. 2010;17:428–36. doi: 10.1097/PAP.0b013e3181f8b028.CrossRefPubMedGoogle Scholar
  10. 10.
    Hamilton SR, Liu B, Parsons RE, Papadopoulos N, Jen J, Powell SM, et al. The molecular basis of Turcot’s syndrome. N Engl J Med. 1995;332:839–47. doi: 10.1056/NEJM199503303321302.CrossRefPubMedGoogle Scholar
  11. 11.
    Fallen T, Wilson M, Morlan B, Lindor NM. Desmoid tumors—a characterization of patients seen at Mayo Clinic 1976–1999. Fam Cancer. 2006;5:191–4. doi: 10.1007/s10689-005-5959-5.CrossRefPubMedGoogle Scholar
  12. 12.
    Gardner EJ, Richards RC. Multiple cutaneous and subcutaneous lesions occurring simultaneously with hereditary polyposis and osteomatosis. Am J Hum Genet. 1953;5:139–47.PubMedCentralPubMedGoogle Scholar
  13. 13.
    Spirio L, Olschwang S, Groden J, Robertson M, Samowitz W, Joslyn G, et al. Alleles of the APC gene: an attenuated form of familial polyposis. Cell. 1993;75:951–7.CrossRefPubMedGoogle Scholar
  14. 14.
    Knudsen AL, Bisgaard ML, Bulow S. Attenuated familial adenomatous polyposis (AFAP). A review of the literature. Fam Cancer. 2003;2:43–55.CrossRefPubMedGoogle Scholar
  15. 15.
    Alkhouri N, Franciosi JP, Mamula P. Familial adenomatous polyposis in children and adolescents. J Pediatr Gastroenterol Nutr. 2010;51:727–32. doi: 10.1097/MPG.0b013e3181e1a224.CrossRefPubMedGoogle Scholar
  16. 16.
    Parc Y, Piquard A, Dozois RR, Parc R, Tiret E. Long-term outcome of familial adenomatous polyposis patients after restorative coloproctectomy. Ann Surg. 2004;239:378–82.PubMedCentralCrossRefPubMedGoogle Scholar
  17. 17.
    Al-Sukhni W, Aronson M, Gallinger S. Hereditary colorectal cancer syndromes: familial adenomatous polyposis and lynch syndrome. Surg Clin North Am. 2008;88(4):819–844 vii. doi: 10.1016/j.suc.2008.04.012.CrossRefPubMedGoogle Scholar
  18. 18.
    Latchford A, Volikos E, Johnson V, Rogers P, Suraweera N, Tomlinson I, et al. APC mutations in FAP-associated desmoid tumours are non-random but not ‘just right’. Hum Mol Genet. 2007;16:78–82. doi: 10.1093/hmg/ddl442.CrossRefPubMedGoogle Scholar
  19. 19.
    Nieuwenhuis MH, Mathus-Vliegen EM, Baeten CG, Nagengast FM, van der Bijl J, van Dalsen AD, et al. Evaluation of management of desmoid tumours associated with familial adenomatous polyposis in Dutch patients. Br J Cancer. 2011;104:37–42. doi: 10.1038/sj.bjc.6605997.PubMedCentralCrossRefPubMedGoogle Scholar
  20. 20.
    Robson ME, Storm CD, Weitzel J, Wollins DS, Offit K. American Society of Clinical Oncology policy statement update: genetic and genomic testing for cancer susceptibility. J Clin Oncol. 2010;28:893–901. doi: 10.1200/JCO.2009.27.0660.CrossRefPubMedGoogle Scholar
  21. 21.
    Lefevre JH, Rodrigue CM, Mourra N, Bennis M, Flejou JF, Parc R, et al. Implication of MYH in colorectal polyposis. Ann Surg. 2006;244:874–9. doi: 10.1097/01.sla.0000246937.54435.50. discussion 879-880.PubMedCentralCrossRefPubMedGoogle Scholar
  22. 22.
    Soravia C, Berk T, Madlensky L, Mitri A, Cheng H, Gallinger S, et al. Genotype-phenotype correlations in attenuated adenomatous polyposis coli. Am J Hum Genet. 1998;62:1290–301. doi: 10.1086/301883.PubMedCentralCrossRefPubMedGoogle Scholar
  23. 23.
    Wallis YL, Morton DG, McKeown CM, Macdonald F. Molecular analysis of the APC gene in 205 families: extended genotype-phenotype correlations in FAP and evidence for the role of APC amino acid changes in colorectal cancer predisposition. J Med Genet. 1999;36:14–20.PubMedCentralPubMedGoogle Scholar
  24. 24.
    Sieber OM, Tomlinson IP, Lamlum H. The adenomatous polyposis coli (APC) tumor suppressor -genetics, function and disease. Mol Med Today. 2000;6:462–9.CrossRefPubMedGoogle Scholar
  25. 25.
    Laken SJ, Petersen GM, Gruber SB, Oddoux C, Ostrer H, Giardiello FM, et al. Familial colorectal cancer in Ashkenazim due to a hypermutable tract in APC. Nat Genet. 1997;17:79–83. doi: 10.1038/ng0997-79.CrossRefPubMedGoogle Scholar
  26. 26.
    Kerr SE, Thomas CB, Thibodeau SN, Ferber MJ, Halling KC. APC germline mutations in individuals being evaluated for familial adenomatous polyposis: a review of the Mayo Clinic experience with 1591 consecutive tests. J Mol Diagn. 2013;15:31–43.CrossRefPubMedGoogle Scholar
  27. 27.
    Nielsen M, Bik E, Hes FJ, Breuning MH, Vasen HF, Bakker E, et al. Genotype-phenotype correlations in 19 Dutch cases with APC gene deletions and a literature review. Eur J Hum Genet. 2007;15:1034–42. doi: 10.1038/sj.ejhg.5201871.CrossRefPubMedGoogle Scholar
  28. 28.
    Friedl W, Caspari R, Sengteller M, Uhlhaas S, Lamberti C, Jungck M, et al. Can APC mutation analysis contribute to therapeutic decisions in familial adenomatous polyposis? Experience from 680 FAP families. Gut. 2001;48:515–21.PubMedCentralCrossRefPubMedGoogle Scholar
  29. 29.
    Westerman AM, Entius MM, de Baar E, Boor PP, Koole R, van Velthuysen ML, et al. Peutz-Jeghers syndrome: 78-year follow-up of the original family. Lancet. 1999;353:1211–5.CrossRefPubMedGoogle Scholar
  30. 30.
    Jeghers H, Mc KV, Katz KH. Generalized intestinal polyposis and melanin spots of the oral mucosa, lips and digits; a syndrome of diagnostic significance. N Engl J Med. 1949;241:1031–6. doi: 10.1056/NEJM194912292412601.CrossRefPubMedGoogle Scholar
  31. 31.
    Hamilton SR, Aaltonen LA. Pathology and genetics of tumours of the digestive system. In: Kleihues P, Sobin LH, editors. World Health Organization classification of tumours. Lyon, France: IARC Press; 2000. p. 251.Google Scholar
  32. 32.
    Giardiello FM, Brensinger JD, Tersmette AC, Goodman SN, Petersen GM, Booker SV, et al. Very high risk of cancer in familial Peutz-Jeghers syndrome. Gastroenterology. 2000;119:1447–53.CrossRefPubMedGoogle Scholar
  33. 33.
    van Lier MG, Wagner A, Mathus-Vliegen EM, Kuipers EJ, Steyerberg EW, van Leerdam ME. High cancer risk in Peutz-Jeghers syndrome: a systematic review and surveillance recommendations. Am J Gastroenterol. 2010;105:1258–64. doi: 10.1038/ajg.2009.725. author reply 1265.CrossRefPubMedGoogle Scholar
  34. 34.
    Hearle N, Schumacher V, Menko FH, Olschwang S, Boardman LA, Gille JJ, et al. Frequency and spectrum of cancers in the Peutz-Jeghers syndrome. Clin Cancer Res. 2006;12:3209–15. doi: 10.1158/1078-0432.CCR-06-0083.CrossRefPubMedGoogle Scholar
  35. 35.
    Jass JR, Williams CB, Bussey HJ, Morson BC. Juvenile polyposis–a precancerous condition. Histopathology. 1988;13:619–30.CrossRefPubMedGoogle Scholar
  36. 36.
    McCarthy PM, Piehler JM, Schaff HV, Pluth JR, Orszulak TA, Vidaillet Jr HJ, et al. The significance of multiple, recurrent, and “complex” cardiac myxomas. J Thorac Cardiovasc Surg. 1986;91:389–96.PubMedGoogle Scholar
  37. 37.
    van Lier MG, Westerman AM, Wagner A, Looman CW, Wilson JH, de Rooij FW, et al. High cancer risk and increased mortality in patients with Peutz-Jeghers syndrome. Gut. 2011;60:141–7. doi: 10.1136/gut.2010.223750.CrossRefPubMedGoogle Scholar
  38. 38.
    Beggs AD, Latchford AR, Vasen HF, Moslein G, Alonso A, Aretz S, et al. Peutz-Jeghers syndrome: a systematic review and recommendations for management. Gut. 2010;59:975–86. doi: 10.1136/gut.2009.198499.CrossRefPubMedGoogle Scholar
  39. 39.
    Wei C, Amos CI, Zhang N, Wang X, Rashid A, Walker CL, et al. Suppression of Peutz-Jeghers polyposis by targeting mammalian target of rapamycin signaling. Clin Cancer Res. 2008;14:1167–71. doi: 10.1158/1078-0432.CCR-07-4007.CrossRefPubMedGoogle Scholar
  40. 40.
    Hemminki A, Markie D, Tomlinson I, Avizienyte E, Roth S, Loukola A, et al. A serine/threonine kinase gene defective in Peutz-Jeghers syndrome. Nature. 1998;391:184–7. doi: 10.1038/34432.CrossRefPubMedGoogle Scholar
  41. 41.
    Jenne DE, Reimann H, Nezu J, Friedel W, Loff S, Jeschke R, et al. Peutz-Jeghers syndrome is caused by mutations in a novel serine threonine kinase. Nat Genet. 1998;18:38–43. doi: 10.1038/ng0198-38.CrossRefPubMedGoogle Scholar
  42. 42.
    Volikos E, Robinson J, Aittomaki K, Mecklin JP, Jarvinen H, Westerman AM, et al. LKB1 exonic and whole gene deletions are a common cause of Peutz-Jeghers syndrome. J Med Genet. 2006;43, e18. doi: 10.1136/jmg.2005.039875.PubMedCentralCrossRefPubMedGoogle Scholar
  43. 43.
    Aretz S, Stienen D, Uhlhaas S, Loff S, Back W, Pagenstecher C, et al. High proportion of large genomic STK11 deletions in Peutz-Jeghers syndrome. Hum Mutat. 2005;26:513–9. doi: 10.1002/humu.20253.CrossRefPubMedGoogle Scholar
  44. 44.
    Mehenni H, Gehrig C, Nezu J, Oku A, Shimane M, Rossier C, et al. Loss of LKB1 kinase activity in Peutz-Jeghers syndrome, and evidence for allelic and locus heterogeneity. Am J Hum Genet. 1998;63:1641–50.PubMedCentralCrossRefPubMedGoogle Scholar
  45. 45.
    Tiainen M, Vaahtomeri K, Ylikorkala A, Makela TP. Growth arrest by the LKB1 tumor suppressor: induction of p21(WAF1/CIP1). Hum Mol Genet. 2002;11:1497–504.Google Scholar
  46. 46.
    Karuman P, Gozani O, Odze RD, Zhou XC, Zhu H, Shaw R, et al. The Peutz-Jegher gene product LKB1 is a mediator of p53-de pendent cell death. Mol Cell. 2001;7:1307–19.Google Scholar
  47. 47.
    Morton DG, Roos JM, Kemphues KJ. par-4, a gene required for cytoplasmic localization and determination of specific cell types in Caenorhabditis elegans embryogenesis. Genetics. 1992;130:771–90.PubMedCentralPubMedGoogle Scholar
  48. 48.
    Alessi DR, Sakamoto K, Bayascas JR. LKB1-dependent signaling pathways. Annu Rev Biochem. 2006;75:137–63. doi: 10.1146/annurev.biochem.75.103004.142702.CrossRefPubMedGoogle Scholar
  49. 49.
    Lin-Marq N, Borel C, Antonarakis SE. Peutz-Jeghers LKB1 mutants fail to activate GSK-3beta, preventing it from inhibiting Wnt signaling. Mol Genet Genomics. 2005;273:184–96. doi: 10.1007/s00438-005-1124-y.CrossRefPubMedGoogle Scholar
  50. 50.
    Corradetti MN, Inoki K, Bardeesy N, DePinho RA, Guan KL. Regulation of the TSC pathway by LKB1: evidence of a molecular link between tuberous sclerosis complex and Peutz-Jeghers syndrome. Genes Dev. 2004;18:1533–8. doi: 10.1101/gad.1199104.PubMedCentralCrossRefPubMedGoogle Scholar
  51. 51.
    Mehenni H, Resta N, Guanti G, Mota-Vieira L, Lerner A, Peyman M, et al. Molecular and clinical characteristics in 46 families affected with Peutz-Jeghers syndrome. Dig Dis Sci. 2007;52:1924–33. doi: 10.1007/s10620-006-9435-3.CrossRefPubMedGoogle Scholar

Copyright information

© Springer International Publishing Switzerland 2016

Authors and Affiliations

  1. 1.Department of Laboratory Medicine and Pathology, Laboratory GeneticsMayo ClinicRochesterUSA

Personalised recommendations