Genetic profiling in der Diagnostik des hereditären Prostatakarzinoms – wo stehen wir?

Zusammenfassung

Prostatakrebs weist im Vergleich zu anderen Tumorentitäten ein heterogenes genetisches Profil auf. Dementsprechend sind auch Mutationen, die das Prostatakarzinomrisiko erhöhen, vielfältig. Manche genetische Varianten fallen bei der Risikoerhöhung nur milde ins Gewicht. Andere Genmutationen (BRCA1 /2; HOXB13) erhöhen das Risiko jedoch teils erheblich. Insgesamt ist die Wahrscheinlichkeit für einen nicht familiär vorbelasteten Mann, ein Träger von Mutationen zu sein, welche mit einem erhöhten PCa-Risiko assoziiert sind, niedrig. Ist aber die familiäre Belastung durch in jungem Alter erkrankte Verwandte oder eine bereits bekannte Mutation in der Familie vorhanden, so steigt auch diese Wahrscheinlichkeit an. In diesen Fällen sollte die genetische Beratung und Testung in Betracht gezogen werden. Insbesondere soll hier an BRCA1 /2-Mutationen und HOXB13-Mutationen gedacht werden. Für die breite Bevölkerungsmasse kann genetic profiling bislang jedoch nicht die PSA-Wert-Bestimmung, mpMRT der Prostata und/oder die Prostatabiopsie im Rahmen der Vorsorge oder des diagnostischen Algorithmus ersetzen. Lediglich können Männer bei Vorliegen der mit PCa assoziierten Mutationen einem engmaschigeren und früheren Screening unterzogen werden und ggf. früher eine definitive Therapie erhalten.

Abstract

Prostate cancer has a heterogeneous genetic profile compared with other tumour entities. Accordingly, there are also various mutations that increase the risk of prostate cancer. Some genetic variants only have a mild impact, whereas other gene mutations (BRCA1 /2; HOXB13) may increase the risk significantly. All in all, a man with a negative family history is unlikely to be a carrier of mutations that are associated with an increased risk of PCa. However, this likelihood increases if the family history is positive for a known mutation or if there are relatives who were affected at an early age. In such cases, genetic counselling and testing should be considered, with a particular focus on BRCA1/2 mutations and HOXB13 mutations. However, genetic profiling has not had the potential to replace PSA testing, mpMRI of the prostate gland and/or prostate biopsies as part of cancer screening or the diagnostic algorithm in the general population. The presence of mutations associated with PCa merely allows patients to undergo screening earlier and in tighter intervals and possibly receive earlier definitive treatment.

Schlüsselwörter

Diagnostik - Genanalyse - Prostatakarzinom

Keywords

prostate cancer - diagnosis - genetic profiling

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