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MC1R variants increased the risk of sporadic cutaneous melanoma in darker‐pigmented C aucasians: A pooled‐analysis from the M‐SKIP project
Author(s) -
Pasquali Elena,
GarcíaBorrón José C.,
Fargnoli Maria Concetta,
Gandini Sara,
Maisonneuve Patrick,
Bagnardi Vincenzo,
Specchia Claudia,
Liu Fan,
Kayser Manfred,
Nijsten Tamar,
Nagore Eduardo,
Kumar Rajiv,
Hansson Johan,
Kanetsky Peter A.,
Ghiorzo Paola,
Debniak Tadeusz,
Branicki Wojciech,
Gruis Nelleke A.,
Han Jiali,
Dwyer Terry,
Blizzard Leigh,
Landi Maria Teresa,
Palmieri Giuseppe,
Ribas Gloria,
Stratigos Alexander,
Council M. Laurin,
Autier Philippe,
Little Julian,
NewtonBishop Julia,
Sera Francesco,
Raimondi Sara
Publication year - 2014
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.29018
Subject(s) - melanoma , odds ratio , medicine , eye color , genotype , dermatology , phenotype , relative risk , skin cancer , risk factor , cancer , confidence interval , genetics , biology , gene , cancer research
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.