@article{2983000,
    title = "MC1R variants in childhood and adolescent melanoma: a retrospective pooled analysis of a multicentre cohort",
    author = "Pellegrini, C. and Botta, F. and Massi, D. and Martorelli, C. and Facchetti, F. and Gandini, S. and Maisonneuve, P. and Avril, M.-F. and Demenais, F. and Bressac-de Paillerets, B. and Hoiom, V. and Cust, A.E. and Anton-Culver, H. and Gruber, S.B. and Gallagher, R.P. and Marrett, L. and Zanetti, R. and Dwyer, T. and Thomas, N.E. and Begg, C.B. and Berwick, M. and Puig, S. and Potrony, M. and Nagore, E. and Ghiorzo, P. and Menin, C. and Manganoni, A.M. and Rodolfo, M. and Brugnara, S. and Passoni, E. and Sekulovic, L.K. and Baldini, F. and Guida, G. and Stratigos, A. and Ozdemir, F. and Ayala, F. and Fernandez-de-Misa, R. and Quaglino, P. and Ribas, G. and Romanini, A. and Migliano, E. and Stanganelli, I. and Kanetsky, P.A. and Pizzichetta, M.A. and García-Borrón, J.C. and Nan, H. and Landi, M.T. and Little, J. and Newton-Bishop, J. and Sera, F. and Fargnoli, M.C. and Raimondi, S. and Alaibac, M. and Ferrari, A. and Valeri, B. and Sicher, M. and Mangiola, D. and Nazzaro, G. and Tosti, G. and Mazzarol, G. and Giudice, G. and Ribero, S. and Astrua, C. and Mazzoni, L. and Orlow, I. and Mujumdar, U. and Hummer, A. and Busam, K. and Roy, P. and Canchola, R. and Clas, B. and Cotignola, J. and Monroe, Y. and Armstrong, B. and Kricker, A. and Litchfield, M. and Tucker, P. and Stephens, N. and Switzer, T. and Theis, B. and From, L. and Chowdhury, N. and Vanasse, L. and Purdue, M. and Northrup, D. and Rosso, S. and Sacerdote, C. and Leighton, N. and Gildea, M. and Bonner, J. and Jeter, J. and Klotz, J. and Wilcox, H. and Weiss, H. and Millikan, R. and Mattingly, D. and Player, J. and Tse, C.-K. and Rebbeck, T. and Walker, A. and Panossian, S. and Setlow, R. and Mohrenweiser, H. and Autier, P. and Han, J. and Caini, S. and Hofman, A. and Kayser, M. and Liu, F. and Nijsten, T. and Uitterlinden, A.G. and Kumar, R. and Bishop, T. and Elliott, F. and Lazovich, D. and Polsky, D. and Hansson, J. and Pastorino, L. and Gruis, N.A. and Bouwes Bavinck, J.N. and Aguilera, P. and Badenas, C. and Carrera, C. and Gimenez-Xavier, P. and Malvehy, J. and Puig-Butille, J.A. and Tell-Marti, G. and Blizzard, L. and Cochrane, J. and Branicki, W. and Debniak, T. and Morling, N. and Johansen, P. and Mayne, S. and Bale, A. and Cartmel, B. and Ferrucci, L. and Pfeiffer, R. and Palmieri, G. and Kypreou, K. and Bowcock, A. and Cornelius, L. and Council, M.L. and Motokawa, T. and Anno, S. and Helsing, P. and Andresen, P.A. and Guida, S. and Wong, T.H. and IMI Study Group and GEM Study Group and M-SKIP Study Group",
    journal = "The Lancet Child and Adolescent Health",
    year = "2019",
    volume = "3",
    number = "5",
    pages = "332-342",
    publisher = "Elsevier B.V.",
    doi = "10.1016/S2352-4642(19)30005-7",
    keywords = "melanocortin 1 receptor;  MC1R protein, human;  melanocortin 1 receptor;  tumor marker, adolescent;  adult;  aged;  Article;  Australia;  Canada;  cancer risk;  cancer susceptibility;  case control study;  childhood disease;  clinical assessment;  cohort analysis;  comparative study;  controlled study;  female;  France;  gene frequency;  gene function;  genetic analysis;  genetic association;  genetic variability;  Greece;  high risk patient;  human;  Italy;  major clinical study;  male;  MC1R gene;  melanoma;  molecular pathology;  Netherlands;  prevalence;  retrospective study;  risk factor;  Serbia;  signal transduction;  Spain;  Sweden;  Turkey (republic);  United States;  child;  genetic polymorphism;  genetic predisposition;  genetics;  germline mutation;  melanoma;  meta analysis;  middle aged;  odds ratio;  skin tumor;  statistical model, Adolescent;  Adult;  Aged;  Biomarkers, Tumor;  Case-Control Studies;  Child;  Female;  Genetic Predisposition to Disease;  Germ-Line Mutation;  Humans;  Logistic Models;  Male;  Melanoma;  Middle Aged;  Odds Ratio;  Polymorphism, Genetic;  Receptor, Melanocortin, Type 1;  Retrospective Studies;  Skin Neoplasms",
    abstract = "Background: Germline variants in the melanocortin 1 receptor gene (MC1R) might increase the risk of childhood and adolescent melanoma, but a clear conclusion is challenging because of the low number of studies and cases. We assessed the association of MC1R variants with childhood and adolescent melanoma in a large study comparing the prevalence of MC1R variants in child or adolescent patients with melanoma to that in adult patients with melanoma and in healthy adult controls. Methods: In this retrospective pooled analysis, we used the M-SKIP Project, the Italian Melanoma Intergroup, and other European groups (with participants from Australia, Canada, France, Greece, Italy, the Netherlands, Serbia, Spain, Sweden, Turkey, and the USA) to assemble an international multicentre cohort. We gathered phenotypic and genetic data from children or adolescents diagnosed with sporadic single-primary cutaneous melanoma at age 20 years or younger, adult patients with sporadic single-primary cutaneous melanoma diagnosed at age 35 years or older, and healthy adult individuals as controls. We calculated odds ratios (ORs) for childhood and adolescent melanoma associated with MC1R variants by multivariable logistic regression. Subgroup analysis was done for children aged 18 or younger and 14 years or younger. Findings: We analysed data from 233 young patients, 932 adult patients, and 932 healthy adult controls. Children and adolescents had higher odds of carrying MC1R r variants than did adult patients (OR 1·54, 95% CI 1·02–2·33), including when analysis was restricted to patients aged 18 years or younger (1·80, 1·06–3·07). All investigated variants, except Arg160Trp, tended, to varying degrees, to have higher frequencies in young patients than in adult patients, with significantly higher frequencies found for Val60Leu (OR 1·60, 95% CI 1·05–2·44; p=0·04) and Asp294His (2·15, 1·05–4·40; p=0·04). Compared with those of healthy controls, young patients with melanoma had significantly higher frequencies of any MC1R variants. Interpretation: Our pooled analysis of MC1R genetic data of young patients with melanoma showed that MC1R r variants were more prevalent in childhood and adolescent melanoma than in adult melanoma, especially in patients aged 18 years or younger. Our findings support the role of MC1R in childhood and adolescent melanoma susceptibility, with a potential clinical relevance for developing early melanoma detection and preventive strategies. Funding: SPD-Pilot/Project-Award-2015; AIRC-MFAG-11831. © 2019 Elsevier Ltd"
}