Human Genetics

, Volume 126, Issue 4, pp 499–510 | Cite as

Genetic risk factors for melanoma

  • Kathrine Damm Meyle
  • Per GuldbergEmail author
Review Article


The genetic basis of melanoma is complex and has both inherited and acquired components. Different genomic approaches have been used to identify a number of inherited risk factors, which can be stratified by penetrance and prevalence. Rare high-penetrance factors are expressed in familial clustering of melanoma and include mutations in CDKN2A (encoding p16INK4a and p14ARF) and CDK4. These genes are involved in cell-cycle arrest and melanocyte senescence and are nearly invariably targeted by somatic mutations during melanoma progression. Low-penetrance factors are common in the general population and include single-nucleotide polymorphisms in or near MC1R, ASIP, TYR and TYRP1. These genes are major determinants of hair and skin pigmentation, but their role in melanoma development remains unclear. This review describes the efforts that have led to the current understanding of melanoma susceptibility as the result of complex gene–gene and gene–environment interactions. Despite the significant advances, the majority of familial cases remain unaccounted for.


Melanoma BRAF Mutation Melanoma Risk Melanoma Development Oculocutaneous Albinism 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



Work that forms the basis of this discussion is supported by grants from the Danish Cancer Society, the Neye Foundation and the Novo Nordisk Foundation.


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© Springer-Verlag 2009

Authors and Affiliations

  1. 1.Institute of Cancer BiologyDanish Cancer SocietyCopenhagenDenmark

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