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.

Original languageEnglish
Pages (from-to)332-342
Number of pages11
JournalThe Lancet Child and Adolescent Health
Volume3
Issue number5
DOIs
Publication statusPublished - May 1 2019

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Receptor, Melanocortin, Type 1
Melanoma
Genes
Odds Ratio
Serbia
Skin
Greece

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Developmental and Educational Psychology

Cite this

MC1R variants in childhood and adolescent melanoma : a retrospective pooled analysis of a multicentre cohort. / IMI Study Group; GEM Study Group; M-SKIP Study Group.

In: The Lancet Child and Adolescent Health, Vol. 3, No. 5, 01.05.2019, p. 332-342.

Research output: Contribution to journalArticle

IMI Study Group ; GEM Study Group ; M-SKIP Study Group. / MC1R variants in childhood and adolescent melanoma : a retrospective pooled analysis of a multicentre cohort. In: The Lancet Child and Adolescent Health. 2019 ; Vol. 3, No. 5. pp. 332-342.
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title = "MC1R variants in childhood and adolescent melanoma: a retrospective pooled analysis of a multicentre cohort",
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.",
author = "{IMI Study Group} and {GEM Study Group} and {M-SKIP Study Group} and Cristina Pellegrini and Francesca Botta and Daniela Massi and Claudia Martorelli and Fabio Facchetti and Sara Gandini and Patrick Maisonneuve and Avril, {Marie Fran{\cc}oise} and Florence Demenais and {Bressac-de Paillerets}, Brigitte and Veronica Hoiom and Cust, {Anne E.} and Hoda Anton-Culver and Gruber, {Stephen B.} and Gallagher, {Richard P.} and Loraine Marrett and Roberto Zanetti and Terence Dwyer and Thomas, {Nancy E.} and Begg, {Colin B.} and Marianne Berwick and Susana Puig and Miriam Potrony and Eduardo Nagore and Paola Ghiorzo and Chiara Menin and Manganoni, {Ausilia Maria} and Monica Rodolfo and Sonia Brugnara and Emanuela Passoni and Sekulovic, {Lidija Kandolf} and Federica Baldini and Gabriella Guida and Alexandros Stratigos and Fezal Ozdemir and Fabrizio Ayala and Ricardo Fernandez-de-Misa and Pietro Quaglino and Emilia Migliano and Ignazio Stanganelli and Pizzichetta, {Maria Antonietta} and Sara Raimondi and Andrea Ferrari and Barbara Valeri and Gianluca Nazzaro and Giulio Tosti and Giovanni Mazzarol and Sara Gandini and Cristina Carrera and Stefania Guida",
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TY - JOUR

T1 - MC1R variants in childhood and adolescent melanoma

T2 - a retrospective pooled analysis of a multicentre cohort

AU - IMI Study Group

AU - GEM Study Group

AU - M-SKIP Study Group

AU - Pellegrini, Cristina

AU - Botta, Francesca

AU - Massi, Daniela

AU - Martorelli, Claudia

AU - Facchetti, Fabio

AU - Gandini, Sara

AU - Maisonneuve, Patrick

AU - Avril, Marie Françoise

AU - Demenais, Florence

AU - Bressac-de Paillerets, Brigitte

AU - Hoiom, Veronica

AU - Cust, Anne E.

AU - Anton-Culver, Hoda

AU - Gruber, Stephen B.

AU - Gallagher, Richard P.

AU - Marrett, Loraine

AU - Zanetti, Roberto

AU - Dwyer, Terence

AU - Thomas, Nancy E.

AU - Begg, Colin B.

AU - Berwick, Marianne

AU - Puig, Susana

AU - Potrony, Miriam

AU - Nagore, Eduardo

AU - Ghiorzo, Paola

AU - Menin, Chiara

AU - Manganoni, Ausilia Maria

AU - Rodolfo, Monica

AU - Brugnara, Sonia

AU - Passoni, Emanuela

AU - Sekulovic, Lidija Kandolf

AU - Baldini, Federica

AU - Guida, Gabriella

AU - Stratigos, Alexandros

AU - Ozdemir, Fezal

AU - Ayala, Fabrizio

AU - Fernandez-de-Misa, Ricardo

AU - Quaglino, Pietro

AU - Migliano, Emilia

AU - Stanganelli, Ignazio

AU - Pizzichetta, Maria Antonietta

AU - Raimondi, Sara

AU - Ferrari, Andrea

AU - Valeri, Barbara

AU - Nazzaro, Gianluca

AU - Tosti, Giulio

AU - Mazzarol, Giovanni

AU - Gandini, Sara

AU - Carrera, Cristina

AU - Guida, Stefania

PY - 2019/5/1

Y1 - 2019/5/1

N2 - 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.

AB - 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.

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