VANCOUVER, B.C. — Genetic studies suggest that certain people are susceptible to melanomas caused by early, minimal sun exposure, according to speakers at the Sixth World Congress on Melanoma.
The problem with explaining melanoma risk solely by sunlight exposure has always been that, while it is true that melanoma rates in fair-skinned people increase the closer they live to the equator, it is also true that indoor workers get more melanomas than do outdoor workers, said David Whiteman, M.D., chair of the population and clinical sciences division at the Queensland (Australia) Institute for Medical Research.
And every physician knows that younger patients have more melanomas on the trunk than on the perpetually sun-exposed areas of the head and neck, he added. The theory that intermittent exposure is worse for melanoma than is constant exposure has been only partially satisfactory.
On the basis of evidence that younger people tend to get melanomas more frequently on unexposed sites, and older people get melanomas on exposed sites, Dr. Whiteman and his colleagues investigated a group of 306 melanoma patients. They compared those with head and neck melanomas with those with trunk melanomas.
The results showed that the individuals with head and neck melanomas were more likely to report high levels of sun exposure, often occupational. These patients also were more likely to have previous skin cancers or actinic keratoses; low nevus counts; and, in melanomas examined histologically by the investigators, a low probability of nevi remnants.
The individuals with trunk melanomas tended to show the opposite: They had mostly recreational sun exposure, high nevus counts, and a high likelihood of nevi remnants in their melanomas.
The data strongly suggest that there are two types of persons who get melanoma: those without a genetic susceptibility who need high sun exposure, and those with a genetic susceptibility, Dr. Whiteman said.
“This is just a hypothesis, and like all hypotheses, it needs to be tested,” he said.
BRAF mutations might be central to sun and melanoma risk, said Janet Maldonado, M.D., a second-year dermatology resident at the University of California, San Francisco. BRAF is a gene involved in the Ras pathway, which, among other things, mediates cellular proliferation.
In a study she conducted, Dr. Maldonado looked at BRAF mutations in 126 cases of melanoma, and found that the mutation was common when the melanoma was on skin without much sun damage (56%), but uncommon in melanomas from sun-damaged skin (11%).
Other investigations also have shown that true congenital nevi rarely have a BRAF mutation, whereas nevi that arise early in young children and could be confused with congenital nevi often do. This finding suggests that sunlight is necessary for creating BRAF mutations and that certain people are susceptible.
Other research has shown that melanomas that arise on skin without sun damage tend to have BRAF mutations, and melanomas on sun-damaged skin tend to have increased copies of the cyclin D gene, located on chromosome 11, Dr. Maldonado said.
This new information on sun risk, genetics, and melanoma may lead to new targeted treatments, and maybe a susceptibility test, commented Martin Weinstock, M.D., a professor of dermatology at Brown University, Providence, R.I.
Although the association between mutation and melanoma suggests certain individuals are at greater risk from sun exposure than others, it does not mean doctors should stop warning people about too much sun since sunlight is implicated in both types of melanoma identified.
The finding also reinforces the need for public education about the importance of skin self-examination.