MC1R variants increase melanoma risk in families with CDKN2A mutations: a meta-analysis

Eur J Cancer. 2010 May;46(8):1413-20. doi: 10.1016/j.ejca.2010.01.027. Epub 2010 Feb 26.


Aim of the study: We performed a meta-analysis to assess whether MC1R variants increase the risk of melanoma in CDKN2A mutation carriers of melanoma-prone families.

Methods: Data from 96 CDKN2A-positive melanoma-prone families from seven independent populations of Europe, United States and Australia were included in the analysis. Summary risk estimates were calculated by random-effect models. We explored between-study heterogeneity and publication bias. Association between MC1R variants and age at diagnosis was assessed by the non-parametric Wilcoxon test.

Results: CDKN2A mutation carriers with 1 MC1R variant showed a double melanoma risk as compared to CDKN2A mutation carriers without MC1R variants (Summary OR; 95%CI: 2.2; 1.1-4.5). MC1R heterozygous subjects had no significantly higher melanoma risk than wild-type subjects (1.6; 0.5-5.4) while carriers of multiple MC1R variants had a more than four-times higher melanoma risk (4.6; 1.3-16.4). Carriers of red hair colour (RHC) variants showed an increased melanoma risk with a Summary OR of 3.5 (95%CI: 1.3-9.9). CDKN2A mutation carriers with MC1R variants had a statistically significant lower median age at melanoma diagnosis than CDKN2A mutation carriers with no MC1R variants (37years versus 47years, p-value<0.0001).

Conclusion: MC1R variants significantly increase penetrance of CDKN2A mutations in melanoma-prone families, especially with respect to multiple MC1R variants and to RHC variants. A significant anticipation of melanoma diagnosis is observed in CDKN2A mutation carriers with MC1R variants.

Publication types

  • Meta-Analysis
  • Review

MeSH terms

  • Australia
  • Cyclin-Dependent Kinase Inhibitor p16 / genetics*
  • Europe
  • Female
  • Genetic Predisposition to Disease / genetics
  • Genetic Variation
  • Humans
  • Male
  • Melanoma / genetics*
  • Mutation
  • Odds Ratio
  • Pedigree
  • Receptor, Melanocortin, Type 1 / genetics*
  • Skin Neoplasms / genetics*
  • United States


  • Cyclin-Dependent Kinase Inhibitor p16
  • Receptor, Melanocortin, Type 1