Polymorphisms of the BRAF gene predispose males to malignant melanoma

Peter Meyer1, Consolato Sergi2, Claus Garbe3
1Department of Dermatology, University Hospital of Tuebingen, Tuebingen; Institute of Human Genetics, University Hospital of Tuebingen, Tuebingen; Genefinder Technologies Ltd., Munich, Germany
2Directorate of Laboratory Medicine, Bristol Royal Infirmary, Bristol, United Kingdom
3Department of Dermatology, University Hospital of Tuebingen, Tuebingen, Germany
DOI: 10.1186/1477-3163-2-7


The incidence of malignant melanoma has rapidly increased in recent years. Evidence points to the role of inheritance in melanoma development, but specific genetic risk factors are not well understood. Recent reports indicate a high prevalence of somatic mutations of the BRAF gene in melanomas and melanocytic nevi. Here we report that germ-line single nucleotide polymorphisms (SNPs) in BRAF are significantly associated with melanoma in German males, but not females. At-risk haplotypes of BRAF are shown. Based upon their frequencies, we estimate that BRAF could account for a proportion attributable risk of developing melanoma of 4% in the German population. The causal variant has yet to be determined. The burden of disease associated with this variant is greater than that associated with the major melanoma susceptibility locus C DKN2A , which has an estimated attributable risk of less than 1%.

Keywords: Melanoma, BRAF , Single Nucleotide Polymorphism (SNP), Predisposition, Molecular Genetics, Association Study, Familial, Sporadic, Gene.