Molekulare Mechanismen der kutanen Photokarzinogenese: ein Update

Zusammenfassung

UV-Strahlung gilt als primäre Ursache der Photokarzinogenese und trägt somit zur Entwicklung von kutanen Hautkrebsentitäten wie Plattenepithelkarzinom, Basalzellkarzinom und Melanom bei. Durch UV-Strahlung entstehen einerseits typische DNA-Photoprodukte und andererseits indirekte DNA-Schäden durch reaktive Sauerstoffspezies. UV-bedingte DNA-Schäden werden durch die Nukleotid-Exzisions-Reparatur behoben, die somit der Bildung von Mutationen und der Hautkrebsentwicklung entgegenwirkt. Durch Mutationen werden Tumorsuppressorgene inaktiviert und wachstumsfördernde Signalwege aktiviert, die die normale Zellzyklusprogression stören. Abhängig von der jeweilig zugrunde liegenden Hautkrebsentität, sind bestimmte Gene häufiger betroffen als andere. Basalzellkarzinome weisen häufig Patched- oder Smoothened-Mutationen auf, die den Sonic hedgehog-Signalweg beeinflussen. Plattenepithelkarzinome zeigen vermehrt TP53-Mutationen. Weitere Mutationen umfassen den epidermalen Wachstumsfaktorrezeptor, RAS, FYN und CDKN2A. In Melanomen konnten vor allem UV-induzierte Mutationen in TP53 und CDKN2A nachgewiesen werden. Zudem tragen UV-induzierte Entzündungsprozesse zur Photokarzinogenese bei. Neuere Studien konnten einen Einfluss von Zitrusfruchtkonsum, Alkoholkonsum, Hormonersatztherapien und oralen Kontrazeptiva auf die Photokarzinogenese feststellen. Präventive Maßnahmen gegen UV-bedingte Karzinogenese beinhalten den adäquaten Gebrauch von Sonnenschutz und regelmäßige Hautkrebsvorsorgeuntersuchungen.

Abstract

UV radiation is acknowledged to be the primary cause for photocarcinogenesis and therefore contributes to the development of skin cancer entities such as squamous cell carcinoma, basal cell carcinoma, and melanoma. Typical DNA-photoproducts and indirect DNA damage through reactive oxygen species are the results of UV radiation. UV-induced DNA damages are repaired by nucleotide excision repair, which consequently counteracts the development of mutations and skin cancerogenesis. Tumor suppressor genes are inactivated by mutation and growth-promoting pathways are activated so that the normal cell cycle progression is disrupted. Depending on the skin cancer entity some genes are more often affected than others. In basal cell carcinoma mutations in Patched or Smoothened are common and affect the Sonic hedgehog pathway. In SCC TP53 mutations are prevalent as well as mutations of the epidermal growth factor receptor, RAS, FYN, and CDKN2A. UV-induced mutations of TP53 and CDKN2A are frequent in melanoma. UV-induced inflammatory processes facilitate photocarcinogenesis. Recent studies showed a connection between citrus consumption, alcohol consumption, hormone replacement therapy, oral contraceptives, and photocarcinogenesis. Preventive measures include adequate use of sun protection and skin cancer screening at regular intervals.

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