Der Gastroenterologe

, Volume 3, Issue 2, pp 112–118 | Cite as

Hereditäres Kolonkarzinom

Klinik und molekulargenetische Diagnostik
Schwerpunkt

Zusammenfassung

Das kolorektale Karzinom (KRK) stellt mit etwa 70.000 Neuerkrankungen pro Jahr die zweithäufigste Tumorentität in Deutschland dar. In 20–30% liegt eine positive Familienanamnese vor. Etwa 2–5% aller KRK entstehen auf dem Boden einer im engeren Sinne erblichen Krebsdisposition. Die häufigste Form des hereditären KRK ist das HNPCC-Syndrom (Lynch-Syndrom). Seltener ist die familiäre adenomatöse Polyposis (FAP). Sehr selten sind hamartomatöse Polyposis-Syndrome (Peutz-Jeghers-Syndrom und familiäre juvenile Polyposis). Die autosomal-rezessiv erbliche multiple adenomatöse Polyposis kommt als Differenzialdiagnose zum Lynch-Syndrom und der attenuierten FAP in Betracht. Neben erhöhten Risiken für KRK besteht bei fast allen Formen ein erhöhtes Risiko extrakolonischer Neoplasien. Durch die Aufdeckung der genetischen Grundlagen erblicher KRK-Formen kann heute in den betroffenen Familien mit molekulargenetischen Methoden festgestellt werden, ob Angehörige die Tumordisposition geerbt haben noch bevor sich Krankheitssymptome entwickeln.

Schlüsselwörter

Hereditäres kolorektales Karzinom Genetik Früherkennung HNPCC FAP 

Hereditary colorectal cancer

Clinical and molecular genetic diagnostics

Abstract

Colorectal cancer (CRC) is the 2nd most common cancer in Germany (incidence 70,000 individuals each year). In 20–30% of all cases, a positive familial history is present, and in 2–5% there is a monogenetic background. The most common form of hereditary CRC is hereditary nonpolyposis colorectal cancer (HNPCC), also called Lynch syndrome. Less frequent are familial adenomatous polyposis coli (FAP) and the hamartomatous polyposis syndromes (Peutz–Jeghers syndrome and juvenile polyposis syndrome). Multiple colorectal adenoma syndrome (MAP) is inherited in an autosomal recessive manner and is an important differential diagnosis for Lynch syndrome and attenuated FAP. In all of these syndromes, individuals have a higher risk of developing CRC as well as a broad spectrum of malignancies outside the colorectum. With the identification of genetic background associated with hereditary CRC, at-risk persons now have the chance to know their individual risk before they develop malignancies.

Keywords

Hereditary colorectal cancer Genetic Early diagnosis HNPCC FAP 

Notes

Interessenkonflikt

Der korrespondierende Autor gibt an, dass kein Interessenkonflikt besteht.

Literatur

  1. 1.
    Agnifili A, Verzaro R, Gola P et al. (1999) Juvenile polyposis: case report and assessment of the neoplastic risk in 271 patients reported in the literature. Dig Surg 16: 161–166PubMedCrossRefGoogle Scholar
  2. 2.
    Al-Tassan N, Chmiel NH, Maynard J et al. (2002) Inherited variants of MYH associated with somatic G: C–>T: A mutations in colorectal tumors. Nat Genet 30: 227–232PubMedCrossRefGoogle Scholar
  3. 3.
    Bulow S, Bjork J, Christensen IJ et al. (2004) Duodenal adenomatosis in familial adenomatous polyposis. Gut 53: 381–386PubMedCrossRefGoogle Scholar
  4. 4.
    Bulow C, Vasen H, Jarvinen H et al. (2000) Ileorectal anastomosis is appropriate for a subset of patients with familial adenomatous polyposis. Gastroenterology 119: 1454–1460PubMedCrossRefGoogle Scholar
  5. 5.
    Burt RW, Leppert MF, Slattery ML et al. (2004) Genetic testing and phenotype in a large kindred with attenuated familial adenomatous polyposis. Gastroenterology 127: 444–451PubMedCrossRefGoogle Scholar
  6. 6.
    Jong AE de, Hendriks YM, Kleibeuker JH et al. (2006) Decrease in mortality in Lynch syndrome families because of surveillance. Gastroenterology 130: 665–671PubMedCrossRefGoogle Scholar
  7. 7.
    Friedl W, Uhlhaas S, Schulmann K et al. (2002) Juvenile polyposis: massive gastric polyposis is more common in MADH4 mutation carriers than in BMPR1A mutation carriers. Hum Genet 111: 108–111PubMedCrossRefGoogle Scholar
  8. 8.
    Galle TS, Juel K, Bulow S (1999) Causes of death in familial adenomatous polyposis. Scand J Gastroenterol 34: 808–812PubMedCrossRefGoogle Scholar
  9. 9.
    Giardiello FM, Welsh SB, Hamilton SR et al. (1987) Increased risk of cancer in the Peutz-Jeghers syndrome. N Engl J Med 316: 1511–1514PubMedCrossRefGoogle Scholar
  10. 10.
    Groves CJ, Saunders BP, Spigelman AD, Phillips RK (2002) Duodenal cancer in patients with familial adenomatous polyposis (FAP): results of a 10 year prospective study. Gut 50: 636–641PubMedCrossRefGoogle Scholar
  11. 11.
    Hampel H, Frankel WL, Martin E et al. (2005) Screening for the Lynch syndrome (hereditary nonpolyposis colorectal cancer). N Engl J Med 352: 1851–1860PubMedCrossRefGoogle Scholar
  12. 12.
    Hampel H, Stephens JA, Pukkala E et al. (2005) Cancer risk in hereditary nonpolyposis colorectal cancer syndrome: later age of onset. Gastroenterology 129: 415–421PubMedGoogle Scholar
  13. 13.
    Handra-Luca A, Condroyer C, Moncuit C de et al. (2005) Vessels‘ morphology in SMAD4 and BMPR1A-related juvenile polyposis. Am J Med Genet 138: 113–117CrossRefGoogle Scholar
  14. 14.
    Hearle N, Schumacher V, Menko FH et al. (2006) Frequency and spectrum of cancers in the Peutz-Jeghers syndrome. Clin Cancer Res 12: 3209–3215PubMedCrossRefGoogle Scholar
  15. 15.
    Jarvinen HJ, Aarnio M, Mustonen H et al. (2000) Controlled 15-year trial on screening for colorectal cancer in families with hereditary nonpolyposis colorectal cancer. Gastroenterology 118: 829–834PubMedCrossRefGoogle Scholar
  16. 16.
    Jass JR, Williams CB, Bussey HJ, Morson BC (1988) Juvenile polyposis – a precancerous condition. Histopathology 13: 619–630PubMedCrossRefGoogle Scholar
  17. 17.
    Lynch HT, Boland CR, Gong G et al. (2006) Phenotypic and genotypic heterogeneity in the Lynch syndrome: diagnostic, surveillance and management implications. Eur J Hum Genet 14: 390–402PubMedCrossRefGoogle Scholar
  18. 18.
    Sassatelli R, Bertoni G, Serra L et al. (1993) Generalized juvenile polyposis with mixed pattern and gastric cancer. Gastroenterology 104: 910–915PubMedGoogle Scholar
  19. 19.
    Schmiegel W, Pox C, Adler G et al. (2004) S3-Leitlinien-Konferenz „Kolorektales Karzinom“ 2004. Z Gastroenterol 42: 1129–1177PubMedCrossRefGoogle Scholar
  20. 20.
    Schmeler KM, Lynch HT, Chen LM et al. (2006) Prophylactic surgery to reduce the risk of gynecologic cancers in the Lynch syndrome. N Engl J Med 354: 261–269PubMedCrossRefGoogle Scholar
  21. 21.
    Schulmann K, Engel C, Propping P, Schmiegel W (2008) Small bowel cancer risk in HNPCC. Gut, in pressGoogle Scholar
  22. 22.
    Schulmann K, Hollerbach S, Kraus K et al. (2005) Feasibility and diagnostic utility of video capsule endoscopy for the detection of small bowel polyps in patients with hereditary polyposis syndromes. Am J Gastroenterol 100: 27–37PubMedCrossRefGoogle Scholar
  23. 23.
    Sieber OM, Lipton L, Crabtree M et al. (2003) Multiple colorectal adenomas, classic adenomatous polyposis, and germ-line mutations in MYH. N Engl J Med 348: 791–799PubMedCrossRefGoogle Scholar
  24. 24.
    Spigelman AD, Williams CB, Talbot IC et al. (1989) Upper gastrointestinal cancer in patients with familial adenomatous polyposis. Lancet 2: 783–785PubMedCrossRefGoogle Scholar
  25. 25.
    Umar A, Boland CR, Terdiman JP et al. (2004) Revised Bethesda Guidelines for hereditary nonpolyposis colorectal cancer (Lynch syndrome) and microsatellite instability. J Natl Cancer Inst 96: 261–268PubMedCrossRefGoogle Scholar
  26. 26.
    Vasen HF, Mecklin JP, Khan PM, Lynch HT (1991) The International Collaborative Group on Hereditary Non-Polyposis Colorectal Cancer (ICG-HNPCC). Dis Colon Rectum 34: 424–425PubMedCrossRefGoogle Scholar
  27. 27.
    Vasen HF, Watson P, Mecklin JP, Lynch HT (1999) New clinical criteria for hereditary nonpolyposis colorectal cancer (HNPCC, Lynch syndrome) proposed by the International Collaborative group on HNPCC. Gastroenterology 116: 1453–1456PubMedCrossRefGoogle Scholar
  28. 28.
    Walpole IR, Cullity G (1989) Juvenile polyposis: a case with early presentation and death attributable to adenocarcinoma of the pancreas. Am J Med Genet 32: 1–8PubMedCrossRefGoogle Scholar
  29. 29.
    Wang L, Baudhuin LM, Boardman LA et al. (2004) MYH mutations in patients with attenuated and classic polyposis and with young-onset colorectal cancer without polyps. Gastroenterology 127: 9–16. Erratum in: Gastroenterology (2004) 127: 1651Google Scholar
  30. 30.
    Watanabe A, Nagashima H, Motoi M, Ogawa K (1979) Familial juvenile polyposis of the stomach. Gastroenterology 77: 148–151PubMedGoogle Scholar

Copyright information

© Springer Medizin Verlag 2008

Authors and Affiliations

  1. 1.KnappschaftskrankenhausRuhr-Universität Bochum,Medizinische UniversitätsklinikBochumDeutschland
  2. 2.Abteilung für HumangenetikRuhr-Universität BochumBochumDeutschland

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