title: MC1R variants increased the risk of sporadic cutaneous melanoma in darker-pigmented Caucasians: a pooled-analysis from the M-SKIP project.
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.
authors.affiliation: Division of Epidemiology and Biostatistics, European Institute of Oncology, Milan, Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: Pasquali
authors.forename: José C
authors.initials: JC
authors.lastname: García-Borrón
authors.forename: Maria Concetta
authors.initials: MC
authors.lastname: Fargnoli
authors.forename: Sara
authors.initials: S
authors.lastname: Gandini
authors.forename: Patrick
authors.initials: P
authors.lastname: Maisonneuve
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Bagnardi
authors.forename: Claudia
authors.initials: C
authors.lastname: Specchia
authors.forename: Fan
authors.initials: F
authors.lastname: Liu
authors.forename: Manfred
authors.initials: M
authors.lastname: Kayser
authors.forename: Tamar
authors.initials: T
authors.lastname: Nijsten
authors.forename: Eduardo
authors.initials: E
authors.lastname: Nagore
authors.forename: Rajiv
authors.initials: R
authors.lastname: Kumar
authors.forename: Johan
authors.initials: J
authors.lastname: Hansson
authors.forename: Peter A
authors.initials: PA
authors.lastname: Kanetsky
authors.forename: Paola
authors.initials: P
authors.lastname: Ghiorzo
authors.forename: Tadeusz
authors.initials: T
authors.lastname: Debniak
authors.forename: Wojciech
authors.initials: W
authors.lastname: Branicki
authors.forename: Nelleke A
authors.initials: NA
authors.lastname: Gruis
authors.forename: Jiali
authors.initials: J
authors.lastname: Han
authors.forename: Terry
authors.initials: T
authors.lastname: Dwyer
authors.forename: Leigh
authors.initials: L
authors.lastname: Blizzard
authors.forename: Maria Teresa
authors.initials: MT
authors.lastname: Landi
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Palmieri
authors.forename: Gloria
authors.initials: G
authors.lastname: Ribas
authors.forename: Alexander
authors.initials: A
authors.lastname: Stratigos
authors.forename: M Laurin
authors.initials: ML
authors.lastname: Council
authors.forename: Philippe
authors.initials: P
authors.lastname: Autier
authors.forename: Julian
authors.initials: J
authors.lastname: Little
authors.forename: Julia
authors.initials: J
authors.lastname: Newton-Bishop
authors.forename: Francesco
authors.initials: F
authors.lastname: Sera
authors.forename: Sara
authors.initials: S
authors.lastname: Raimondi
mesh_terms: D020022:Genetic Predisposition to Disease; D006801:Humans; D008545:Melanoma / Q000209:etiology / Q000235:genetics*; D008875:Middle Aged; D010641:Phenotype; D044102:Receptor, Melanocortin, Type 1 / Q000235:genetics*; D012306:Risk; D012878:Skin Neoplasms / Q000209:etiology / Q000235:genetics*; D012880:Skin Pigmentation; D044465:White People
chemical_list: D044102:Receptor, Melanocortin, Type 1
keywords: genetic epidemiology; melanocortin-1 receptor; melanoma; meta-analysis