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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, Elena and García Borrón, José C. and Fargnoli, Maria Concetta and Gandini, Sara and Maisonneuve, Patrick and Bagnardi, Vincenzo and Specchia, Claudia and Liu, Fan and Kayser, Manfred and Nijsten, Tamar and Nagore, Eduardo and Kumar, Rajiv and Hansson, Johan and Kanetsky, Peter A. and Ghiorzo, Paola and Debniak, Tadeusz and Branicki, Wojciech and Gruis, Nelleke A. and Han, Jiali and Dwyer, Therry and Blizzard, Leigh and Landi, Maria Teresa and Palmieri, Giuseppe and Ribas, Gloria and Stratigos, Alexander and Council, M. Laurin and Autier, Philippe and Little, Julian and Newton Bishop, Julia and Sera, Francesco and Raimondi, Sara (2015) MC1Rvariants increased the risk of sporadic cutaneous melanoma in darker-pigmented Caucasians: a pooled-analysis from the M-SKIP project. International journal of cancer, Vol. 136 (3), p. 618-631. ISSN 0020-7136. eISSN 1097-0215. Article.

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DOI: 10.1002/ijc.29018

Abstract

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.

Item Type:Article
ID Code:10375
Status:Published
Refereed:Yes
Uncontrolled Keywords:Melanocortin-1 receptor, melanoma, meta-analysis, genetic epidemiology
Subjects:Area 06 - Scienze mediche > MED/06 Oncologia medica
Divisions:002 Altri enti e centri di ricerca del Nord Sardegna > CNR-Consiglio Nazionale delle Ricerche > Istituto di chimica biomolecolare, Sassari
Publisher:Wiley
ISSN:0020-7136
eISSN:1097-0215
Deposited On:25 Nov 2014 13:54

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