Melanoma is a type of skin cancer. Melanoma tumors form in the skin’s pigment-producing cells or melanocytes. Growing evidence points to complex interactions between genetics and environmental exposures that contribute to the risk of developing melanoma. Ultraviolet (UV) radiation from the sun causes genetic mutations in melanocytes. This sun exposure interacts with genetic variations that may make people more or less vulnerable to such DNA damage. For example, genetic variations that control skin color or the cell’s ability to repair DNA, and that influence how easily people develop sunburn, all affect whether UV damage leads to melanoma. However, some forms of melanoma are not caused by sun exposure at all.
Most of the genetic variations linked to melanoma have a small effect on the risk of developing the disease. So, it is unlikely that these genes alone cause melanoma. Few studies have been able to map the complex interactions between genes and the environment that lead to melanoma. So far, it has been unclear if there are different genetic mechanisms that lead to an increased risk for sun-exposure linked melanoma and non-sun linked melanoma.
Now, Ferguson et al. show that variations in the genes involved in DNA repair during normal cell growth are linked to non-sun linked melanoma. Sun-linked melanoma, on the other hand, was associated with genes involved in the production of proteins in part of the cell called ribosomes. In the experiments, the effects of both UV light and various genetic variations were assessed across many different strains of mice. Mutations that impair the cell’s ability to repair UV-induced DNA damage or that contribute to excessive inflammation in response to sunburn did not increase melanoma susceptibility in these experiments.
Ferguson et al. show that the amount of UV-induced DNA damage alone does not explain melanoma risk, which may not always depend on skin pigmentation. The experiments also suggest that non-UV linked melanoma is caused by a different mechanism than sun exposure-linked melanoma. Learning more about different genetic factors that affect the risk of developing different types of melanoma may help scientists develop more specific treatments.