Is there more than one road to melanoma?

Lancet. 2004 Feb 28;363(9410):728-30. doi: 10.1016/S0140-6736(04)15649-3.


Context: Sunlight is the main environmental cause of most cutaneous melanomas. Exposure to intense bursts of ultraviolet radiation, especially in childhood, starts the transformation of benign melanocytes into a malignant phenotype. Paradoxically, outdoor workers have a decreased risk of melanoma compared with indoor workers, suggesting that chronic sunlight exposure can have a protective effect. Further, some melanomas form on sun-exposed regions; others do not. Although some melanomas arise from pre-existing melanocytic naevi (moles), many arise de novo. These observations suggest that melanoma arises from multiple pathways, with initiating and promoting factors differing for each.

Starting point: Janet Maldonado and colleagues recently studied the distribution of BRAF gene mutations in 115 patients with invasive primary melanomas (J Natl Cancer Inst 2003; 95: 1878-80). These researchers found that BRAF mutations were statistically significantly more common in melanomas occurring on intermittently sun-exposed skin than elsewhere. By contrast, BRAF mutations in melanomas on chronically sun-damaged skin were rare. These findings strongly suggest that distinct genetic pathways lead to melanoma. WHERE NEXT? The study of gene-environment interactions is clearly the next arena for epidemiological research into melanoma. The recent identification of polymorphisms in the melanocortin-1 receptor could open up an avenue of investigation into a molecular distinction between those individuals whose melanomas arise on chronic sun-exposed skin from those in whom tumours will develop on sun-protected skin or from melanocytic naevi. If a dual pathway for melanoma is supported by other investigations, public-health messages can be tailored to the population at risk.

Publication types

  • Review

MeSH terms

  • Carcinogens
  • Humans
  • Melanoma / etiology*
  • Melanoma / genetics*
  • Melanoma / prevention & control
  • Mutation / genetics
  • Nevus, Pigmented / genetics
  • Receptor, Melanocortin, Type 1
  • Risk Factors
  • Skin / radiation effects
  • Skin Neoplasms / etiology*
  • Skin Neoplasms / genetics*
  • Skin Neoplasms / prevention & control
  • Sunlight / adverse effects
  • Sunscreening Agents / therapeutic use
  • Ultraviolet Rays / adverse effects


  • Carcinogens
  • Receptor, Melanocortin, Type 1
  • Sunscreening Agents