MC1R variants increased the risk of sporadic cutaneous melanoma in darker-pigmented Caucasians: A pooled-analysis from the M-SKIP project

Elena Pasquali, José C. García-Borrón, Maria Concetta Fargnoli, Sara Gandini, Patrick Maisonneuve, Vincenzo Bagnardi, Claudia Specchia, Fan Liu, Manfred Kayser, Tamar Nijsten, Eduardo Nagore, Rajiv Kumar, Johan Hansson, Peter A. Kanetsky, Paola Ghiorzo, Tadeusz Debniak, Wojciech Branicki, Nelleke A. Gruis, Jiali Han, Terry DwyerLeigh Blizzard, Maria Teresa Landi, Giuseppe Palmieri, Gloria Ribas, Alexander Stratigos, M. Laurin Council, Philippe Autier, Julian Little, Julia Newton-Bishop, Francesco Sera, Sara Raimondi, Saverio Caini, Albert Hofman, Andre G. Uitterlinden, Dominique Scherer, Veronica Hoiom, Lorenza Pastorino, Jennifer Cochrane, Ricardo Fernandez-De-Misa, Niels Morling, Peter Johansen, Ruth Pfeiffer, Katerina Kypreou, Anne Bowcock, Lynn Cornelius, Tomonori Motokawa, Sumiko Anno, Per Helsing, Per Arne Andresen, Terence H. Wong

Research output: Contribution to journalArticlepeer-review


The MC1R gene is a key regulator of skin pigmentation. We aimed to evaluate the association between MC1R variants and the risk of sporadic cutaneous melanoma (CM) within the M-SKIP project, an international pooled-analysis on MC1R, skin cancer and phenotypic characteristics. Data included 5,160 cases and 12,119 controls from 17 studies. We calculated a summary odds ratio (SOR) for the association of each of the nine most studied MC1R variants and of variants combined with CM by using random-effects models. Stratified analysis by phenotypic characteristics were also performed. Melanoma risk increased with presence of any of the main MC1R variants: the SOR for each variant ranged from 1.47 (95%CI: 1.17-1.84) for V60L to 2.74 (1.53-4.89) for D84E. Carriers of any MC1R variant had a 66% higher risk of developing melanoma compared with wildtype subjects (SOR; 95%CI: 1.66; 1.41-1.96) and the risk attributable to MC1R variants was 28%. When taking into account phenotypic characteristics, we found that MC1R-associated melanoma risk increased only for darker-pigmented Caucasians: SOR (95%CI) was 3.14 (2.06-4.80) for subjects with no freckles, no red hair and skin Type III/IV. Our study documents the important role of all the main MC1R variants in sporadic CM and suggests that they have a direct effect on melanoma risk, independently on the phenotypic characteristics of carriers. This is of particular importance for assessing preventive strategies, which may be directed to darker-pigmented Caucasians with MC1R variants as well as to lightly pigmented, fairskinned subjects.

Original languageEnglish
Pages (from-to)618-631
Number of pages14
JournalInternational Journal of Cancer
Issue number3
Publication statusPublished - Feb 15 2015


  • Genetic epidemiology
  • Melanocortin-1 receptor
  • Melanoma
  • Meta-analysis

ASJC Scopus subject areas

  • Cancer Research
  • Oncology


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