Ultraviolet Radiation Carcinogenesis at a Glance
- Ultraviolet radiation (UVR) from the sun is the most prevalent carcinogen in humans, particularly among Caucasians.
- Annual increases continue in the incidence of all types of skin cancer.
- The importance of exposure timing, dose rate, and total UVR exposure differ between the types of skin cancer.
- Sunlight leaves characteristic mutations that identify key molecular and cellular steps in skin tumor development.
- DNA repair, apoptosis, and cell signaling pathways are critical to preventing skin cancer, and UVR affects each of these processes.
- Genetic polymorphisms in genes for DNA repair, melanin, and free radical scavenging affect skin cancer risk.
- Novel, pathway-based approaches to prevent or treat skin cancer are being developed.
- Educational and behavioral approaches are key to minimizing skin cancer rates in the future.
Skin cancer offers a very clear picture of how a carcinogen causes human neoplasia. The basic principles of carcinogen exposure and slow development were discovered when Sir Percivall Pott traced scrotal cancers in adults to childhood employment as a chimney sweep1 and they also apply to sunlight-induced cancers.2,3 The process begins with carcinogen exposure, DNA damage, and failure to repair DNA or failure to apoptotically eliminate a damaged cell.4–7 A mutant gene arises in a single cell which then expands into a mutant clone.8 Rare cells of the clone repeat this carcinogenesis cycle to generate mutations in additional genes. Sunlight acts at each of these steps.
The lifetime expectation of skin cancer in Australia is ∼60%.9 In the southern United States and Hawaii, nonmelanoma skin cancers exceed all other cancers combined.10–12 Basal and squamous cell carcinomas (BCC and SCC), and an SCC precursor, actinic keratosis (AK), are most frequent on sun-exposed skin, in outdoor workers, and at lower latitudes.13–16 SCCs increase more quickly with dose of sun exposure or nearness to the equator than BCCs, and occur later in life, implying that SCC requires more sun-related steps.16–20 In contrast, one-third of BCCs occur on body sites having only intermittent sun exposure, such as the trunk and legs.16,21
Melanoma also depends on sunlight. The relation to latitude is clear,22–25 yet it is often stated that the predilection for the back and lower legs makes the relation to sunlight uncertain. This predilection likely reflects the large surface area of back and legs. When expressed as lesions per unit area, melanomas are 10–20-fold more frequent on the ears of males and face than on intermittently exposed sites such as the lower legs in women, shoulders, back, or neck.25,26 Melanomas are rare on the buttocks and soles. Melanoma appears to have two distinct origins:
A chronic sun damage (CSD) etiology affects the head and neck and is associated with chronic elastosis—a classic indicator ...