MC1R variation and melanoma risk in relation to host/clinical and environmental factors in CDKN2A positive and negative melanoma patients

Exp Dermatol. 2012 Sep;21(9):718-20. doi: 10.1111/j.1600-0625.2012.01549.x.


Host, environmental and genetic factors differently modulate cutaneous melanoma (CM) risk across populations. Currently, the main genetic risk determinants are germline mutations in the major known high-risk susceptibility genes, CDKN2A and CDK4, and variants of the low-risk gene MC1R, which is key in the pigmentation process. This case-control study aimed at investigating the influence of the main host and environmental risk factors and of MC1R variation on CM risk in 390 CDKN2A-negative and 49 CDKN2A-positive Italian individuals. Multivariate analysis showed that MC1R variation, number of nevi and childhood sunburns doubled CM risk in CDKN2A-negative individuals. In CDKN2A-positive individuals, family history of CM and presence of atypical nevi, rather than MC1R status, modified risk (20.75- and 2.83-fold, respectively). Occupational sun exposure increased CM risk (three to sixfold) in both CDKN2A-negative and CDKN2A-positive individuals, reflecting the occupational habits of the Ligurian population and the geographical position of Liguria.

Publication types

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

MeSH terms

  • Adolescent
  • Adult
  • Age Factors
  • Aged
  • Aged, 80 and over
  • Case-Control Studies
  • Confidence Intervals
  • Female
  • Genes, p16*
  • Humans
  • Italy
  • Male
  • Melanoma / etiology
  • Melanoma / genetics*
  • Middle Aged
  • Multivariate Analysis
  • Mutation
  • Nevus / pathology
  • Occupational Exposure / adverse effects*
  • Odds Ratio
  • Receptor, Melanocortin, Type 1 / genetics*
  • Risk Factors
  • Skin Neoplasms / etiology
  • Skin Neoplasms / genetics*
  • Sunburn / complications
  • Sunlight / adverse effects*
  • Young Adult


  • Receptor, Melanocortin, Type 1