TY - JOUR
TI - MC1R variants in childhood and adolescent melanoma: a retrospective pooled analysis of a multicentre cohort
AU - Pellegrini, C.
AU - Botta, F.
AU - Massi, D.
AU - Martorelli, C.
AU - Facchetti, F.
AU - Gandini, S.
AU - Maisonneuve, P.
AU - Avril, M.-F.
AU - Demenais, F.
AU - Bressac-de Paillerets, B.
AU - Hoiom, V.
AU - Cust, A.E.
AU - Anton-Culver, H.
AU - Gruber, S.B.
AU - Gallagher, R.P.
AU - Marrett, L.
AU - Zanetti, R.
AU - Dwyer, T.
AU - Thomas, N.E.
AU - Begg, C.B.
AU - Berwick, M.
AU - Puig, S.
AU - Potrony, M.
AU - Nagore, E.
AU - Ghiorzo, P.
AU - Menin, C.
AU - Manganoni, A.M.
AU - Rodolfo, M.
AU - Brugnara, S.
AU - Passoni, E.
AU - Sekulovic, L.K.
AU - Baldini, F.
AU - Guida, G.
AU - Stratigos, A.
AU - Ozdemir, F.
AU - Ayala, F.
AU - Fernandez-de-Misa, R.
AU - Quaglino, P.
AU - Ribas, G.
AU - Romanini, A.
AU - Migliano, E.
AU - Stanganelli, I.
AU - Kanetsky, P.A.
AU - Pizzichetta, M.A.
AU - García-Borrón, J.C.
AU - Nan, H.
AU - Landi, M.T.
AU - Little, J.
AU - Newton-Bishop, J.
AU - Sera, F.
AU - Fargnoli, M.C.
AU - Raimondi, S.
AU - Alaibac, M.
AU - Ferrari, A.
AU - Valeri, B.
AU - Sicher, M.
AU - Mangiola, D.
AU - Nazzaro, G.
AU - Tosti, G.
AU - Mazzarol, G.
AU - Giudice, G.
AU - Ribero, S.
AU - Astrua, C.
AU - Mazzoni, L.
AU - Orlow, I.
AU - Mujumdar, U.
AU - Hummer, A.
AU - Busam, K.
AU - Roy, P.
AU - Canchola, R.
AU - Clas, B.
AU - Cotignola, J.
AU - Monroe, Y.
AU - Armstrong, B.
AU - Kricker, A.
AU - Litchfield, M.
AU - Tucker, P.
AU - Stephens, N.
AU - Switzer, T.
AU - Theis, B.
AU - From, L.
AU - Chowdhury, N.
AU - Vanasse, L.
AU - Purdue, M.
AU - Northrup, D.
AU - Rosso, S.
AU - Sacerdote, C.
AU - Leighton, N.
AU - Gildea, M.
AU - Bonner, J.
AU - Jeter, J.
AU - Klotz, J.
AU - Wilcox, H.
AU - Weiss, H.
AU - Millikan, R.
AU - Mattingly, D.
AU - Player, J.
AU - Tse, C.-K.
AU - Rebbeck, T.
AU - Walker, A.
AU - Panossian, S.
AU - Setlow, R.
AU - Mohrenweiser, H.
AU - Autier, P.
AU - Han, J.
AU - Caini, S.
AU - Hofman, A.
AU - Kayser, M.
AU - Liu, F.
AU - Nijsten, T.
AU - Uitterlinden, A.G.
AU - Kumar, R.
AU - Bishop, T.
AU - Elliott, F.
AU - Lazovich, D.
AU - Polsky, D.
AU - Hansson, J.
AU - Pastorino, L.
AU - Gruis, N.A.
AU - Bouwes Bavinck, J.N.
AU - Aguilera, P.
AU - Badenas, C.
AU - Carrera, C.
AU - Gimenez-Xavier, P.
AU - Malvehy, J.
AU - Puig-Butille, J.A.
AU - Tell-Marti, G.
AU - Blizzard, L.
AU - Cochrane, J.
AU - Branicki, W.
AU - Debniak, T.
AU - Morling, N.
AU - Johansen, P.
AU - Mayne, S.
AU - Bale, A.
AU - Cartmel, B.
AU - Ferrucci, L.
AU - Pfeiffer, R.
AU - Palmieri, G.
AU - Kypreou, K.
AU - Bowcock, A.
AU - Cornelius, L.
AU - Council, M.L.
AU - Motokawa, T.
AU - Anno, S.
AU - Helsing, P.
AU - Andresen, P.A.
AU - Guida, S.
AU - Wong, T.H.
AU - IMI Study Group
AU - GEM Study Group
AU - M-SKIP Study Group
JO - The Lancet Child and Adolescent Health
PY - 2019
VL - 3
TODO - 5
SP - 332-342
PB - Elsevier B.V.
SN - null
TODO - 10.1016/S2352-4642(19)30005-7
TODO - 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
TODO - 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
ER -