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Carcinogenesis: UV Radiation

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Textbook of Aging Skin

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Abstract

The incidence of human skin cancers collectively outnumbers that of all other cancers combined. Ultraviolet radiation (UVR) has long been understood to produce photoproducts in DNA, some of which give rise to specific somatic mutations capable of driving epithelial and melanocytic cancers. Accordingly, the vast numbers of somatic point mutations found in melanoma and basal and squamous cell carcinoma are predominantly base changes associated with UVR. While TP53 and NOTCH1 mutation have emerged as hallmarks of squamous cell carcinomas, as have PTCH mutations in basal cell carcinoma, large-scale sequencing projects are illuminating dozens of other known tumor suppressors and oncogenes mutated at low frequency in both melanomas and nonmelanoma skin cancer. Thus, cells tolerating DNA damage without triggering apoptosis eventually acquire mutations favoring clonal growth, and these populations in turn accumulate additional, lower frequency mutations enhancing oncogenic cell behavior. The process of UV-driven transformation in skin cancers is markedly accelerated not only by deficiencies in DNA repair, but also by immunodeficiency, suggesting that surveillance mechanisms actively eliminate UV-damaged cells, perhaps through T-cell detection of neoepitopes. Genetic factors modulating risk of UV carcinogenesis include resistance conferred by melanin and susceptibility associated with impaired free-radical clearance. Epidemiological efforts have begun validating systemic chemopreventatives, such as caffeine, which may be deployed, in concert with sun protection and avoidance, to further delay UV carcinogenesis.

This chapter is adapted with permission from Ch. 112 of Wolff, E, Goldsmith, L, Katz, S, Gilchrest, B, Paller, A and Leffell, D (eds.), Fitzpatrick’s Dermatology in General Medicine, 7th ed., vol. 1, pp 999–1006, Mc-Graw-Hill, 2007.

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Author information

Authors and Affiliations

  1. Departments of Therapeutic Radiology, Genetics, and Dermatology, Yale School of Medicine, 333 Cedar St./HRT 213, New Haven, CT, 06520-8040, USA

    Douglas E. Brash, Timothy P. Heffernan & Paul Nghiem

  2. Department of Dermatology, University of California at San Francisco, San Francisco, CA, USA

    Raymond J. Cho

Authors
  1. Douglas E. Brash
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  2. Timothy P. Heffernan
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  3. Paul Nghiem
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  4. Raymond J. Cho
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Correspondence to Raymond J. Cho .

Editor information

Editors and Affiliations

  1. Procter & Gamble Co., Cincinnati, Ohio, USA

    Miranda A. Farage

  2. Procter & Gamble Co., Cincinnati, Ohio, USA

    Kenneth W. Miller

  3. Department Dermatology, University of California, San Francisco School of Medicine, San Francisco, California, USA

    Howard I. Maibach

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Brash, D.E., Heffernan, T.P., Nghiem, P., Cho, R.J. (2015). Carcinogenesis: UV Radiation. In: Farage, M., Miller, K., Maibach, H. (eds) Textbook of Aging Skin. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-27814-3_56-2

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  • DOI: https://doi.org/10.1007/978-3-642-27814-3_56-2

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