Exposure to ultraviolet radiation is a well-established risk factor for melanoma in light-skinned populations, but genetic factors also play a role. Studying melanomas that occur on skin with little chronic sun damage, Landi et al. discover an interaction between two genes that contributes to cancer risk. Individuals with allelic variants of the gene encoding the melanocortin-1 receptor (MC1R), which contributes to phenotypic traits such as fair skin, freckling, and red hair, have a much greater risk of developing melanomas with mutations in the BRAF oncogene. The mechanism underlying this association is unclear but appears to be independent of MC1R's effects on pigmentation.
M. T. Landi, J. Bauer, R. M. Pfeiffer, D. E. Elder, B. Hulley, P. Minghetti, D. Calista, P. A. Kanetsky, D. Pinkel, B. C. Bastian, MC1R germline variants confer risk for BRAF-mutant melanoma. Science 313, 521-522 (2006). [Abstract] [Full Text]