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

journal contribution
posted on 2023-05-18, 08:39 authored by Pasquali, E, Garcia-Borron, JC, Fargnoli, MC, Gandini, S, Maisonneuve, P, Bagnardi, V, Specchia, C, Liu, F, Kayser, M, Nijsten, T, Nagore, E, Kumar, R, Hansson, J, Kanetsky, PA, Ghiorzo, P, Debniak, T, Branicki, W, Gruis, NA, Han, J, Dwyer, T, Christopher BlizzardChristopher Blizzard, Landi, MT, Palmieri, G, Ribas, G, Stratigos, A, Council, ML, Autier, P, Little, J, Newton-Bishop, J, Sera, F, Raimondi, S
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 wild-type 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, fair-skinned subjects.


Publication title

International Journal of Cancer








Menzies Institute for Medical Research



Place of publication

Div John Wiley & Sons Inc, 605 Third Ave, New York, USA, Ny, 10158-0012

Rights statement

Copyright 2015 UICC

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  • Restricted

Socio-economic Objectives

Clinical health not elsewhere classified

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