medizinische genetik

, Volume 19, Issue 2, pp 210–215 | Cite as

Genetik des Prostatakarzinoms

Schwerpunktthema: Krebs und Genetik
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Zusammenfassung

Das Prostatakarzinom ist der häufigste maligne Tumor des Mannes, und es weist ätiologisch den größten genetischen Einfluss auf. Dennoch konnten bislang keine Gene identifiziert werden, die einen größeren Teil familiärer Fälle erklären und entsprechende Diagnostik ermöglichen. Keimbahnmutationen in 3 aus Kopplungsanalysen hervorgegangenen Genen (ELAC2, RNASEL, MSR1) sind zu selten und in ihrer Penetranz fraglich. Assoziationen zu diversen Genen sind meist schwach und nur für BRCA2 bzw. familiären Brustkrebs klinisch von Bedeutung. Infolge der extremen Heterogenität muss sich die genetische Beratung auf Risikoschätzungen aus dem Stammbaum stützen, wobei bereits ein betroffener Verwandter 1. Grades zu einem relevanten Risiko führt.

Schlüsselwörter

Prostatakarzinom Hereditäres Prostatakarzinom ELAC2 RNASEL MSR1 

Genetics of prostate cancer

Abstract

Prostate cancer is the most frequent malignancy in males and its etiology is strongly influenced by genetic factors. Nevertheless, no mutated genes which could be used for diagnosis have been identified in a major proportion of familial cases. Three genes with germline mutations have been identified after linkage analysis (ELAC2, RNASEL, MSR1), but these mutations are very rare and their penetrance is not well defined. The association of most genes with genetic variants is weak, and only BRCA2/familial breast cancer is of clinical relevance. As a consequence of the extreme genetic heterogeneity, diagnostic tools are not available and genetic counseling has to rely on risk estimates from pedigree data in which a single affected first degree relative indicates a relevant risk.

Keywords

Prostate cancer Hereditary prostate cancer ELAC2 RNASEL MSR1 

Literatur

  1. 1.
    Carpten J, Nupponen N, Isaacs S et al. (2002) Germline mutations in the ribonuclease L gene in families showing linkage with HPC1. Nat Genet 30: 181–184CrossRefPubMedGoogle Scholar
  2. 2.
    Carter BS, Bova GS, Beaty TH et al. (1993) Hereditary prostate cancer: epidemiologic and clinical features. J Urol 150: 797–802PubMedGoogle Scholar
  3. 3.
    Cui J, Staples MP, Hopper JL et al. (2001) Segregation analyses of 1,476 population-based Australian families affected by prostate cancer. Am J Hum Genet 68: 1207–1218CrossRefPubMedGoogle Scholar
  4. 4.
    Easton DF, Schaid DJ, Whittemore AS et al. (2003) Where are the prostate cancer genes?-A summary of eight genome wide searches. Prostate 57: 261–269CrossRefPubMedGoogle Scholar
  5. 5.
    Edwards SM, Kote-Jarai Z, et al. (2003) Two percent of men with early-onset prostate cancer harbor germline mutations in the BRCA2 gene. Am J Hum Genet 72: 1–12CrossRefPubMedGoogle Scholar
  6. 6.
    Gong G, Oakley-Girvan I, Wu AH et al. (2002) Segregation analysis of prostate cancer in 1,719 white, African-American and Asian-American families in the United States and Canada. Cancer Causes Control 13: 471–482CrossRefPubMedGoogle Scholar
  7. 7.
    Lichtenstein P, Holm NV, Verkasalo PK et al. (2000) Environmental and heritable factors in the causation of cancer – analyses of cohorts of twins from Sweden, Denmark, and Finland. N Engl J Med 343: 78–85CrossRefPubMedGoogle Scholar
  8. 8.
    Ostrander EA, Stanford JL (2000) Genetics of prostate cancer: too many loci, too few genes. Am J Hum Genet 67: 1367–1375CrossRefPubMedGoogle Scholar
  9. 9.
    Schaid DJ (2004) The complex genetic epidemiology of prostate cancer. Hum Mol Genet 13: R103–R121CrossRefPubMedGoogle Scholar
  10. 10.
    Schaid DJ (2006) Pooled genome linkage scan of aggressive prostate cancer: results from the International Consortium for Prostate Cancer Genetics. Hum Genet 120: 471–485CrossRefPubMedGoogle Scholar
  11. 11.
    Tavtigian SV, Simard J, Teng DH et al. (2001) A candidate prostate cancer susceptibility gene at chromosome 17p. Nat Genet 27: 172–180CrossRefPubMedGoogle Scholar
  12. 12.
    Xu J, Zheng SL, Komiya A et al. (2002) Germline mutations and sequence variants of the macrophage scavenger receptor 1 gene are associated with prostate cancer risk. Nat Genet 32: 321–325CrossRefPubMedGoogle Scholar
  13. 13.
    Xu J, Dimitrov L, Chang BL et al. (2005) A combined genomewide linkage scan of 1,233 families for prostate cancer-susceptibility genes conducted by the international consortium for prostate cancer genetics. Am J Hum Genet 77: 219–229CrossRefPubMedGoogle Scholar

Copyright information

© Springer Medizin Verlag 2007

Authors and Affiliations

  1. 1.Institut für HumangenetikUniversitätsklinikum UlmUlmDeutschland

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