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

Maria Concetta Fargnoli, Sara Gandini, Ketty Peris, Patrick Maisonneuve, Sara Raimondi

Research output: Contribution to journalArticlepeer-review


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 (37 years versus 47 years, 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.

Original languageEnglish
Pages (from-to)1413-1420
Number of pages8
JournalEuropean Journal of Cancer
Issue number8
Publication statusPublished - May 2010


  • Cyclin-dependent kinase inhibitor 2A
  • Familial melanoma
  • Genetic epidemiology
  • Melanocortin-1-receptor

ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Medicine(all)


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