NEW YORKThe association between intermittent but intense sun exposure and malignant melanoma has long been recognized, though the reasons behind it have not been understood. Researchers have now uncovered mechanisms likely to explain why this specific pattern of sun exposure leads to the deadliest form of skin cancer.
Barbara Gilchrest, MD, professor of dermatology, Boston University, and author of Mechanisms of Disease, a review published in the New England Journal of Medicine (April 29, 1999), summarized her findings at an American Academy of Dermatology briefing.
Melanoma typically occurs in areas of the body intermittently exposed to the sun, the middle of the back being the most common site. This is in contrast to squamous cell and basal cell carcinomas, the two most common skin cancers, which tend to occur in regularly sun-exposed areas such as the face, back of the hands, and forearms, and in people with a history of cumulative exposure over the course of many years.
Specific DNA mutations due to ultraviolet damage are involved in all skin cancers, she said, but the difference lies in the mechanism by which the body repairs or counteracts that DNA damage.
Squamous and basal cell carcinomas arise in the keratinocytes, whereas melanoma is a cancer of the melanocytes. When exposed to UV radiation, the most severely damaged keratinocytes undergo apoptosis, while those less severely damaged remain and continue to be vulnerable to mutation with each subsequent exposure. Melanocytes, on the other hand, are highly resistant to apoptosis, possibly because they exist in far fewer numbers than keratinocytes and serve the important and irreplaceable function of producing the protective pigment melanin. This resistance to cell death enables UV-damaged melanocytes to mutate and divide, Dr. Gilchrest said.
Furthermore, later DNA damage in human skin cells may be repaired to an enhanced degree through a process known as the SOS response. The production of specialized repair proteins is increased within 2 to 3 days of an initial damaging sun exposure, and parallels increased production of melanin pigment, resulting in a tan.
The repair process is not perfect, however, and cells with DNA defects continue to accumulate, accounting for the pattern of cumulative damage associated with the nonmelanoma skin cancers.
A large dose of UV, such as results in a severe sunburn rather than gradual tanning, damages keratinocytes and melanocytes alike. The difference is that the highly damaged keratinocytes undergo apoptosis, whereas the melanocytes remain in their damaged state.
According to Dr. Gilchrests hypothesis, intermittent high-dose exposures are expected to give rise to more melanomas than frequent low-dose exposures because the UV injury occurs when the melanocytes DNA-repair capacity is relatively low, the DNA damage is poorly repaired, and all the damaged cells are retained.
The incidence of malignant melanoma has risen 1,900% since 1930, a trend Dr. Gilchrest attributes to the increase in recreational exposure to skin areas left covered in the past. Excessive sun exposure and severe sunburns in the first 10 to 15 years of life can result in a threefold increase in the lifetime risk of developing melanoma, she said.
The Academy urges sun avoidance, the use of protective clothing and a sunscreen with an SPF of at least 15 when the sun cannot be avoided, regular examination of all areas of the skin, and an annual skin examination by a professional.