Zusammenfassung
Hintergrund
Ultraviolette Strahlung kann DNA-Schäden hervorrufen, die, wenn sie nicht durch die Nukleotidexzisionsreparatur (NER) behoben werden, DNA-Mutationen verursachen und somit die Entwicklung von Hautkrebs auslösen können. Defekte im NER-System bilden die Ursache einer Reihe von seltenen genetischen Syndromen.
Fragestellung
Übersicht zum aktuellen Verständnis der Fotokarzinogenese und dazu, wie Defekte im NER-System das Hautkrebsrisiko erhöhen. Des Weiteren wird ein Überblick zu Diagnostik und Therapie des Xeroderma pigmentosum (XP) sowie zu UV-Schutzmaßnahmen gegeben.
Material und Methoden
Zusammenfassung der aktuellen Literatur zu Fotokarzinogenese, NER-Defekt-Syndromen und UV-Schutz.
Ergebnisse
Ein Energietransfer von UV-Strahlung auf DNA bewirkt die Bildung von Cyclobutanpyrimidindimeren (CPD) und Pyrimidin-Pyrimidon-Fotoprodukten (6-4-PP). Werden diese Läsionen nicht repariert, entstehen DNA-Mutationen, die die Krebsentwicklung befördern. Genetische Defekte im NER-System können zu verschiedenen seltenen meist autosomal-rezessiven genetischen Syndromen, wie dem Cockayne-Syndrom (CS), einer Trichothiodystrophie (TTD), dem zerebro-okulo-fazio-skeletalen Syndrom (COFS), dem UV-sensitiven Syndrom (UVSS) und dem XP führen. Die Syndrome sind abhängig vom betroffen Gen des NER-Systems und gehen mit erhöhter UV-Sensitivität, neurologischen Störungen und/oder erhöhtem Hautkrebsrisiko einher. Erste Hautveränderungen treten bei XP-Patienten bereits ab einem Alter von 3 bis 5 Jahren auf, und im Alter von 9 Jahren wird im Median erstmals nichtmelanozytärer Hautkrebs diagnostiziert.
Schlussfolgerungen
Schutzmaßnahmen sind für Patienten mit XP unverzichtbar. Das Beispiel der XP-Patienten zeigt im Zeitraffertempo, wie wichtig auch der UV-Schutz bei allen Kindern ist.
Abstract
Background
Exposure of skin to ultraviolet (UV) radiation can cause DNA damage. An intact nucleotide excision repair (NER) system usually prevents the formation of DNA mutations as a consequence of such lesions; however, defects in the NER system are the cause of a variety of rare genetic syndromes.
Objective
Overview of the current understanding of photocarcinogenesis and how defects in the NER system increase the risk of skin cancer. Furthermore, a brief review of the diagnostics and treatment of xeroderma pigmentosum (XP) as well as UV protection is provided.
Material and methods
A literature search was performed to summarize the current knowledge on photocarcinogenesis, NER defect syndromes and UV protection.
Results
Energy transfer from UV radiation to DNA leads to formation of cyclobutane pyrimidine dimers (CPD) and pyrimidine-pyrimidone (6–4) photoproducts (6–4 PP). If not repaired by NER these DNA lesions are transformed into DNA mutations and drive carcinogenesis. Genetic defects in the NER system are the underlying cause of a variety of rare mostly autosomal recessive genetic syndromes, such as the Cockayne syndrome (CS), trichothiodystrophy (TTD), cerebrooculofacioskeletal (COFS) syndrome, UV-sensitive syndrome (UVSS), and XP depending on which NER gene is affected. These syndromes are associated with increased UV sensitivity, neurological disorders, and/or increased risk of skin cancer. The first skin changes in XP patients usually occur at the age of 3‑5 years and nonmelanoma skin cancer is first diagnosed at a median age of 9 years.
Conclusion
Strict UV protection is essential for patients with rare DNA repair defect syndromes, such as XP. The example of XP shows in time-lapse how important UV protection is for all children.
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Diese Arbeit wurde teilweise durch den Europäischen Sozialfonds (ESF) mit dem Förderkennzeichen ESF/14-BM-A55-0001/18 und dem Ministerium für Bildung, Wissenschaft und Kultur des Landes Mecklenburg-Vorpommern, DFG EM 63/13‑1, die Damp Stiftung, das TBI Projekt „AmbuPlas“ und das Nachwuchsförderprogramm FORUN der Universitätsmedizin Rostock gefördert. Einzelne Passagen des Textes wurden bereits in ähnlicher Form in anderen Publikationen der Arbeitsgruppe der Autoren publiziert.
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M.C. Martens, S. Emmert und L. Boeckmann geben an, dass kein Interessenkonflikt besteht.
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P. Höger, Wilhelmstift
F. Zepp, Mainz
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Martens, M.C., Emmert, S. & Boeckmann, L. Genetisch bedingte UV‑Empfindlichkeit. Monatsschr Kinderheilkd (2021). https://doi.org/10.1007/s00112-020-01115-3
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Schlüsselwörter
- Fotokarzinogenese
- Nukleotidexzisionsreparatur
- Hautkrebs
- Xeroderma pigmentosum
- UV-Schutz
Keywords
- Photocarcinogenesis
- Nucleotide excision repair
- Skin cancer
- Xeroderma pigmentosum
- UV protection