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Science 313 (5786): 521-522

Copyright © 2006 by the American Association for the Advancement of Science

MC1R Germline Variants Confer Risk for BRAF-Mutant Melanoma

Maria Teresa Landi,1*{dagger} Jürgen Bauer,2,3* Ruth M. Pfeiffer,1 David E. Elder,4 Benjamin Hulley,1 Paola Minghetti,5 Donato Calista,5 Peter A. Kanetsky,7 Daniel Pinkel,6 Boris C. Bastian2

Abstract: Germline variants in MC1R, the gene encoding the melanocortin-1 receptor, and sun exposure increase risk for melanoma in Caucasians. The majority of melanomas that occur on skin with little evidence of chronic sun-induced damage (non-CSD melanoma) have mutations in the BRAF oncogene, whereas in melanomas on skin with marked CSD (CSD melanoma) these mutations are less frequent. In two independent Caucasian populations, we show that MC1R variants are strongly associated with BRAF mutations in non-CSD melanomas. In this tumor subtype, the risk for melanoma associated with MC1R is due to an increase in risk of developing melanomas with BRAF mutations.

1 Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Bethesda, MD 20892, USA.
2 Departments of Dermatology and Pathology and Comprehensive Cancer Center, University of California, San Francisco, CA 94143, USA.
3 Department of Dermatology, Eberhard Karls University, 72076 Tübingen, Germany.
4 Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.
5 Department of Dermatology, M. Bufalini Hospital, Cesena, 47023, Italy.
6 Department of Laboratory Medicine, University of California, San Francisco, CA 94143, USA.
7 Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.

* These authors contributed equally to this work.

{dagger} To whom correspondence should be addressed. E-mail: landim{at}

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