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Lancet Child Adolesc Health. 2019 May;3(5):332-342. doi: 10.1016/S2352-4642(19)30005-7. Epub 2019 Mar 12.

MC1R variants in childhood and adolescent melanoma: a retrospective pooled analysis of a multicentre cohort.

Author information

1
Department of Dermatology and Department of Biotechnological and Applied Clinical Sciences, University of L'Aquila, L'Aquila, Italy.
2
Division of Epidemiology and Biostatistics, European Institute of Oncology IRCCS, Milan, Italy; Department of Statistics and Quantitative Methods, University of Milano-Bicocca, Milan, Italy.
3
Division of Pathological Anatomy, Department of Surgery and Translational Medicine, University of Florence, Florence, Italy.
4
Pathology Section, Department of Molecular and Translational Medicine, Spedali Civili di Brescia, University of Brescia, Brescia, Italy.
5
Molecular and Pharmaco-Epidemiology Unit, Department of Experimental Oncology, European Institute of Oncology IRCCS, Milan, Italy.
6
Division of Epidemiology and Biostatistics, European Institute of Oncology IRCCS, Milan, Italy.
7
APHP, Dermatology Department, Hôpital Cochin and Paris Descartes University, Paris, France.
8
Genetic Variation and Human Diseases Unit (UMR-946), Institut National de la Santé et de la Recherche Médicale (INSERM), Paris, France.
9
Department of Biopathology and INSERM, University of Paris-Saclay, Villejuif, France.
10
Department of Oncology and Pathology, Cancer Centre, Karolinska Institutet, Stockholm, Sweden.
11
Sydney School of Public Health and Melanoma Institute Australia, University of Sydney, Sydney, NSW, Australia.
12
Department of Epidemiology, University of California, Irvine, CA, USA.
13
USC Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA, USA.
14
British Columbia Cancer and Department of Dermatology and Skin Science, University of British Columbia, Vancouver, BC, Canada.
15
Cancer Care Ontario, Toronto, ON, Canada.
16
Piedmont Cancer Registry, Centre for Epidemiology and Prevention in Oncology in Piedmont, Turin, Italy.
17
George Institute for Global Health, Nuffield Department of Obstetrics and Gynaecology, University of Oxford, Oxford, UK.
18
Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC, USA.
19
Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
20
Department of Internal Medicine, University of New Mexico Cancer Center, University of New Mexico, Albuquerque, NM, USA.
21
Melanoma Unit, Dermatology Department, Hospital Clinic Barcelona, University of Barcelona, Institut d'Investigacions Biomèdiques August Pi I Sunyer, and CIBER de Enfermedades Raras, Barcelona, Spain.
22
Department of Dermatology, Instituto Valenciano de Oncologia, Valencia, Spain.
23
Department of Internal Medicine and Medical Specialties, University of Genoa and Ospedale Policlinico San Martino, Genoa, Italy.
24
Diagnostic Immunology and Molecular Oncology Unit, Veneto Institute of Oncology, IOV-IRCCS, Padua, Italy.
25
Department of Dermatology, Spedali Civili di Brescia, University of Brescia, Brescia, Italy.
26
Department of Research, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
27
Oncology Unit, Santa Chiara Hospital, Trento, Italy.
28
Department of Pathophysiology and Transplantation, University of Milan, Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.
29
Department of Dermatology, Faculty of Medicine, Military Medical Academy, Belgrade, Serbia.
30
Division of Melanoma, Sarcoma and Rare Cancer, European Institute of Oncology IRCCS, Milan, Italy.
31
Department of Basic Medical Sciences, Neurosciences and Sense Organs, University of Bari Aldo Moro, Bari, Italy.
32
1st Department of Dermatology, Andreas Sygros Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece.
33
Department of Dermatology, Faculty of Medicine, University of Ege, Izmir, Turkey.
34
Melanoma Unit, Cancer Immunotherapy and Innovative Therapies, IRCCS Istituto Nazionale dei Tumori, Fondazione G Pascale, Napoli, Italia.
35
Dermatology Service, University Hospital Nuestra Senora de Candelaria, Santa Cruz de Tenerife, Spain.
36
Dermatologic Clinic, Department of Medical Sciences, University of Torino, Turin, Italy.
37
Department of Medical Oncology and Haematology, Fundación Investigación Clínico de Valencia, INCLIVA Instituto de Investigación Sanitaria, Valencia, Spain.
38
US Ambulatori Melanomi, Sarcomi e Tumori Rari, UO Oncologia Medica 1, Azienda Ospedaliero-Universitaria Santa Chiara, Pisa, Italy.
39
Plastic Surgery, San Gallicano Dermatological Institute, IRCCS, Rome, Italy.
40
Skin Cancer Unit, IRCCS Scientific Institute of Romagna for the Study and Treatment of Cancer and University of Parma, Meldola, Italy.
41
Department of Cancer Epidemiology, H Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA.
42
University of Trieste, Centro di Riferimento Oncologico, IRCCS, Aviano, Italy.
43
Department of Biochemistry, Molecular Biology, and Immunology, University of Murcia and IMIB-Arrixaca, Murcia, Spain.
44
Department of Epidemiology, Richard M Fairbanks School of Public Health, Melvin & Bren Simon Cancer Center, Indiana University, Indianapolis, IN, USA.
45
Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
46
School of Epidemiology and Public Health, University of Ottawa, Ottawa, ON, Canada.
47
Section of Epidemiology and Biostatistics, Institute of Medical Research at St James', University of Leeds, Leeds, UK.
48
Department of Public Health, Environments and Society, London School of Hygiene & Tropical Medicine, London, UK.
49
Molecular and Pharmaco-Epidemiology Unit, Department of Experimental Oncology, European Institute of Oncology IRCCS, Milan, Italy. Electronic address: sara.raimondi@ieo.it.

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.

PMID:
30872112
PMCID:
PMC6942319
[Available on 2020-05-01]
DOI:
10.1016/S2352-4642(19)30005-7

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