Genetics of melanoma predisposition

Oncogene. 2003 May 19;22(20):3053-62. doi: 10.1038/sj.onc.1206445.


Predisposition to melanoma is genetically heterogeneous. Two high penetrance susceptibility genes, CDKN2A and CDK4, have so far been identified and mapping is ongoing to localize and identify others. With the advent of a catalogue of millions of potential DNA polymorphisms, attention is now also being focused on identification of genes that confer a more modest contribution to melanoma risk, such as those encoding proteins involved in pigmentation, DNA repair, cell growth and differentiation or detoxification of metabolites. One such pigmentation gene, MC1R, has not only been found to be a low penetrance melanoma gene but has also been shown to act as a genetic modifier of melanoma risk in individuals carrying CDKN2A mutations. Most recently, an environmental agent, ultraviolet radiation, has also been established as a modifier of melanoma risk in CDKN2A mutation carriers. Hence, melanoma is turning out to be an excellent paradigm for studying gene-gene and gene-environment interactions.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Cyclin-Dependent Kinase 4
  • Cyclin-Dependent Kinases / genetics
  • Cytochrome P-450 CYP2D6 / genetics
  • Epidermal Growth Factor / genetics
  • Genes, p16
  • Genetic Predisposition to Disease*
  • Glutathione Transferase / genetics
  • Humans
  • Melanoma / etiology
  • Melanoma / genetics*
  • Mutation
  • Penetrance
  • Polymorphism, Genetic
  • Proto-Oncogene Proteins*
  • Receptors, Calcitriol / genetics
  • Receptors, Corticotropin / genetics
  • Receptors, Melanocortin
  • Skin Pigmentation / genetics
  • Tumor Suppressor Protein p14ARF / genetics
  • Ultraviolet Rays / adverse effects


  • Proto-Oncogene Proteins
  • Receptors, Calcitriol
  • Receptors, Corticotropin
  • Receptors, Melanocortin
  • Tumor Suppressor Protein p14ARF
  • Epidermal Growth Factor
  • Cytochrome P-450 CYP2D6
  • Glutathione Transferase
  • glutathione S-transferase M1
  • CDK4 protein, human
  • Cyclin-Dependent Kinase 4
  • Cyclin-Dependent Kinases