Hereditäre nicht-polypöse kolorektale Karzinome

 

 Buy Article Permissions and Reprints

Zusammenfassung

Etwa 20 – 25 % aller kolorektalen Karzinome treten familiär gehäuft auf. Bei 4 – 5 % ist die Familienanamnese positiv mit autosomal dominanter Vererbung. Erbliche kolorektale Karzinome sind grundsätzlich in adenomatöse, und die seltenen hyperplastischen, hamartomatösen bzw. juvenilen polypösen Erkrankungen zu differenzieren.

Familien mit hereditären nicht-polypösen kolorektalen Karzinomen (HNPCC; hereditary non-polyposis colorectal cancer) umfassen zwei Tumorentitäten. Zum einen Tumore mit Mikrosatelliteninstabilität und Keimbahnmutation in einem der DNA-Reparaturgene (MSI, Lynch-Syndrom) und zum anderen Tumore ohne Mikrosatelliteninstabilität (MSS). Familien mit Lynch-Syndrom weisen gegenüber Familien mit MSS-Tumoren zusätzliche assoziierte Tumorerkrankungen, ein früheres Erkrankungsalter und ein höheres Risiko für syn- und metachrone Zweitneoplasien auf.

Summary

Familial clusternig is found in 20–25% of all cases with colorectal cancer (CRC), 4–5% revealing autosomal dominant inheritance. Hereditary CRC develops from adenomatous, hyperplastic hamartomatous juvenile lesions. Hereditory nonpolyposis colorectal cancer includes two genetically different tumor entities, those with and without microsatellite instability in the corresponding tumors. Those with such instability and with germ-line mutation in DNA mismatch repair genes (Lynch syndrome) have additional neoplasms, an earlier age at onset and a higher risk for syn- and metachronous cancers.

Literatur

• 1 Boland C R, Thibodeau S N, Hamilton S R. et al . A 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 cancer.  Cancer Res. 1998;  58 5248-5257
  Google Scholar
• 2 Dove-Edwin I, de Jong A E, Adams J. et al . Prospective results of surveillance colonoscopy in dominant familial colorectal cancer with and without Lynch syndrome.  Gastroenterology. 2006;  130 1995-2000
  Google Scholar
• 3 Engel C, Forberg J, Holinski-Feder E. et al . Novel strategy for optimal sequential application of clinical criteria, immunohistochemistry and microsatellite analysis in the diagnosis of hereditary nonpolyposis colorectal cancer.  Int J Cancer. 2006;  118 115-122
  Google Scholar
• 4 Goecke T, Schulmann K, Engel C. et al . Genotype-phenotype comparison of German MLH1 and MSH2 mutation carriers clinically affected with Lynch syndrome: a report by the German HNPCC Consortium.  J Clin Oncol. 2006;  24 4285-4292
  Google Scholar
• 5 Hampel H, Stephens J A, Pukkala E. et al . Cancer risk in hereditary nonpolyposis colorectal cancer syndrome: later age of onset.  Gastroenterology. 2005;  129 415-421
  Google Scholar
• 6 Herman J G, Umar A, Polyak K. et al . Incidence and functional consequences of hMLH1 promoter hypermethylation in colorectal carcinoma.  Proc Natl Acad Sci U S A. 1998;  95 6870-6875
  Google Scholar
• 7 Hitchins M P, Wong J J, Suthers G. et al . Inheritance of a cancer-associated MLH1 germ-line epimutation.  N Engl J Med. 2007;  356 697-705
  Google Scholar
• 8 Johns L E, Houlston R S. A systematic review and meta-analysis of familial colorectal cancer risk.  Am J Gastroenterol. 2001;  96 2992-3003
  Google Scholar
• 9 Kuismanen S A, Holmberg M T, Salovaara R, de la Chapelle A, Peltomaki P. Genetic and epigenetic modification of MLH1 accounts for a major share of microsatellite-unstable colorectal cancers.  Am J Pathol. 2000;  156 1773-1779
  Google Scholar
• 10 Lindor N M, Rabe K, Petersen G M. et al . Lower cancer incidence in Amsterdam-I criteria families without mismatch repair deficiency: familial colorectal cancer type X.  JAMA. 2005;  293 1979-1985
  Google Scholar
• 11 Morak M, Schackert H K, Rahner N. et al . Further evidence for heritability of an epimutation in one of 12 cases with MLH1 promoter methylation in blood cells clinically displaying HNPCC.  Eur J Hum Genet. 2008;  16 (7) 804-811
  Google Scholar
• 12 Mueller-Koch Y, Vogelsang H, Kopp R. et al . Hereditary non-polyposis colorectal cancer: clinical and molecular evidence for a new entity of hereditary colorectal cancer.  Gut. 2005;  54 1733-1740
  Google Scholar
• 13 Olsson L, Lindblom A. Family history of colorectal cancer in a Sweden county.  Fam Cancer. 2003;  2 87-93
  Google Scholar
• 14 Renkonen-Sinisalo L, Butzow R, Leminen A, Lehtovirta P, Mecklin J P, Jarvinen H J. Surveillance for endometrial cancer in hereditary nonpolyposis colorectal cancer syndrome.  Int J Cancer. 2007;  120 821-824
  Google Scholar
• 15 Salovaara R, Loukola A, Kristo P. et al . Population-based molecular detection of hereditary nonpolyposis colorectal cancer.  J Clin Oncol. 2000;  18 2193-2200
  Google Scholar
• 16 St John D J, McDermott F T, Hopper J L, Debney E A, Johnson W R, Hughes E S. Cancer risk in relatives of patients with common colorectal cancer.  Ann Intern Med. 1993;  118 785-790
  Google Scholar
• 17 Umar A, Boland C R, Terdiman J P. et al . Revised Bethesda Guidelines for hereditary nonpolyposis colorectal cancer (Lynch syndrome) and microsatellite instability.  J Natl Cancer Inst. 2004;  96 261-268
  Google Scholar
• 18 Vasen H F, Mecklin J P, Khan P M, Lynch H T. The International Collaborative Group on Hereditary Non-Polyposis Colorectal Cancer (ICG-HNPCC).  Dis Colon Rectum. 1991;  34 424-425
  Google Scholar
• 19 Vasen H F, Moslein G, Alonso A. et al . Guidelines for the clinical management of Lynch syndrome (hereditary non-polyposis cancer).  J Med Genet. 2007;  44 353-362
  Google Scholar
• 20 Vasen H F, Taal B G, Nagengast F M. et al . Hereditary nonpolyposis colorectal cancer: results of long-term surveillance in 50 families.  Eur J Cancer. 1995;  31A 1145-1148
  Google Scholar
• 21 Vasen H F, Watson P, Mecklin J P, Lynch H T. New clinical criteria for hereditary nonpolyposis colorectal cancer (HNPCC, Lynch syndrome) proposed by the International Collaborative group on HNPCC.  Gastroenterology. 1999;  116 1453-1456
  Google Scholar
• 22 Vasen H F, Wijnen J T, Menko F H. et al . Cancer risk in families with hereditary nonpolyposis colorectal cancer diagnosed by mutation analysis.  Gastroenterology. 1996;  110 1020-1027
  Google Scholar
• 23 Watson P, Vasen H F, Mecklin J P. et al . The risk of extra-colonic, extra-endometrial cancer in the Lynch syndrome.  Int J Cancer. 2008;  123 444-449
  Google Scholar

PD Dr. med. Dipl. chem. Elke Holinski-Feder

Medizinisch Genetisches Zentrum München

Bayerstr. 3 – 5

80335 München