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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


Pasquali, E and Garcia-Borron, JC and Fargnoli, MC and Gandini, S and Maisonneuve, P and Bagnardi, V and Specchia, C and Liu, F and Kayser, M and Nijsten, T and Nagore, E and Kumar, R and Hansson, J and Kanetsky, PA and Ghiorzo, P and Debniak, T and Branicki, W and Gruis, NA and Han, J and Dwyer, T and Blizzard, L and Landi, MT and Palmieri, G and Ribas, G and Stratigos, A and Council, ML and Autier, P and Little, J and Newton-Bishop, J and Sera, F and Raimondi, S, M-SKIP Study Group, MC1R variants increased the risk of sporadic cutaneous melanoma in darker-pigmented Caucasians: a pooled-analysis from the M-SKIP project, International Journal of Cancer, 136, (3) pp. 618-631. ISSN 0020-7136 (2015) [Refereed Article]

Copyright Statement

Copyright 2015 UICC

DOI: doi:10.1002/ijc.29018


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: 1.171.84) for V60L to 2.74 (1.534.89) 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; 1.411.96) 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 (2.064.80) 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.

Item Details

Item Type:Refereed Article
Keywords:melanocortin-1 receptor, melanoma, meta-analysis, genetic epidemiology
Research Division:Health Sciences
Research Group:Epidemiology
Research Field:Epidemiology not elsewhere classified
Objective Division:Health
Objective Group:Clinical health
Objective Field:Clinical health not elsewhere classified
UTAS Author:Blizzard, L (Professor Leigh Blizzard)
ID Code:99337
Year Published:2015
Web of Science® Times Cited:69
Deposited By:Menzies Institute for Medical Research
Deposited On:2015-03-19
Last Modified:2017-11-07

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