Identification of Risk Factors, Exposomics and Genetic Susceptibility of Melanoma in Children, Adolescents and Young Adults (ExpoMel)

Identification of Risk Factors, Exposomics and Genetic Susceptibility of Melanoma in Children, Adolescents and Young Adults - Novel Health Care Strategies for Melanoma in Children, Adolescents and Young Adults (MELCAYA)

The primary objective of this study is the identification of environmental and genetic factors involved in the risk and progression of melanoma in children, adolescents and young adults (CAYA). The secondary objectives are to generate a model integrating the genetic and environmental factors to estimate the risk of developing melanoma and improve the primary prevention of melanoma through evidence-based interpretation of environmental risk.

Study Overview

• Status: Recruiting
• Conditions: Melanoma; Congenital Nevi; Spitzoid Melanoma

Detailed Description

By retrieving data from several epidemiological and clinical registries across Europe it is aimed to integrate and maximize efforts in order to create a large dataset that serves for a comprehensive analysis of genetic and environmental factors influencing the etiology of melanoma in CAYA. The data will be combined with exposome information about climate and pollution for the development of a weighted risk score. Furthermore, germline high risk mutations and germline low-medium risk variants will be analyzed. Genome and transcriptome sequencing of blood and in selected cases tumour will provide the most comprehensive data to create a polygenic risk score for CAYA melanoma. Transcriptome data will help to identify and characterize the effect of variants of unknown significance in coding, intronic as well as regulatory regions. Tumour sequencing can provide additional information on functional relevance of variants, e.g. secondary hits in tumour tissue or second hits in tumour suppressor genes. Such identification will be highly advantageous to design prevention strategies for melanoma development in CAYA.

• Study Type: Observational
• Enrollment (Estimated): 200

Contacts and Locations

• Study Contact: Name: Ines B Brecht, MD, PhD; Phone Number: +49707183773; Email: ines.brecht@med.uni-tuebingen.de
• Study Contact Backup: Name: Christopher Schroeder, MD; Email: christopher.schroeder@med.uni-tuebingen.de

Study Locations

• Germany
  • Düsseldorf, Germany, 40225
    • Active, not recruiting
    • Leibniz Research Institute for Environmental Medicine
• Italy
  • Florence, Italy, 50121
    • Active, not recruiting
    • University of Florence
  • Milan, Italy, 20133
    • Active, not recruiting
    • Istituto Nazionale del Tumori
• Poland
  • Gdańsk, Poland, 80-210
    • Recruiting
    • Medical University of Gdansk
    • Contact: Ewa Bien, MD, PhD
• Spain
  • Barcelona, Spain, 08036
    • Recruiting
    • Hospital Clinic De Barcelona
    • Contact: Susana Puig Sardá, MD, PhD
• Sweden
  • Solna, Sweden, 17177
    • Recruiting
    • Karolinska Institute
    • Contact: Hildur Helgadottir, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult
• Accepts Healthy Volunteers: N/A

• Sampling Method: Non-Probability Sample

Study Population

Due to its registry-based retrospective study, no formal recruitment of patients will occur in ExpoMel. Data and samples will be obtained from the following registries and associated biobanks:

• Catalonia Melanoma Network through Hospital Clinic Barcelona
• The German Registry for Rare Pediatric Tumours (STEP) of the German Society for Pediatric Oncology and Hematology
• Swedish Melanoma Registry (SweMR) through Karolinska Institute
• Public Pathology Database of the Netherlands (PALGA) through Princess Maxima Center for Children OncologyCentral Registry Malignant Melanoma of the German Dermatological Society (CMMR)
• Polish Pediatric Rare Tumor Study group and selected Eastern/Southern Europe countries cooperating within the European Cooperative Study Group for Pediatric Rare Tumors (EXPERT) through the Medical University Gdansk

Description

Inclusion Criteria:

• confirmed melanoma
• age until 30 years old

Exclusion Criteria:

• no available biological material
• no signed informed consent

Study Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort
Classic melanoma; Classic malignant melanoma under the age of 30 years For patients with available biospecimen, the germline genome, transcriptome and in selected cases tumour normal exomes will be sequenced.
Spitzoid melanoma; Spitzoid melanoma under the age of 30 years For patients with available biospecimen, the germline genome, transcriptome and in selected cases tumour normal exomes will be sequenced.
Other melanoma; Other melanoma as melanoma on congenital nevi under the age of 30 years For patients with available biospecimen, the germline genome, transcriptome and in selected cases tumour normal exomes will be sequenced.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Identification of environmental and genetic factors involved in the risk and progression of melanoma in children, adolescents and young adults (CAYA)	By retrieving data from several epidemiological and clinical registries across Europe we aim to create a large dataset that serves for a comprehensive analysis of genetic and environmental factors influencing the etiology of melanoma in CAYA. Data on climate variables such as surface temperature, solar radiation, and air pollutants will be collected from ground-based instruments, such as air quality monitoring stations, and satellites and reanalysis data from the Copernicus Atmosphere Monitoring Service (CAMS). Data analysis from genome sequencing will be done using established bioinformatic pipelines and combined with exposome information about climate and pollution for the development of a weighted risk score.	01.01.2024 - 30.11.2025

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Generating a polygenic risk score for melanoma in CAYA by using the Lindeman-Merenda-Gold (LMG) method	Genome and transcriptome sequencing of blood and in selected cases tumour will provide the most comprehensive data to create a polygenic risk score for melanoma in CAYA. We will develop a weighted risk score for each environmental factor, which comprises the effects of several variables measuring the respective risk factor. Additionally, a weighted risk score for the epigenetic variables will be build. To estimate the relative contribution of environmental and epigenetic factors we will calculate the relative importance (proportion of explained variance) of the weighted risk scores in an ordinary linear regression model using the Lindeman-Merenda-Gold (LMG) method.	01.06.2024 - 31.05.2026
Prevention strategies for melanoma development in CAYA	The detected risk factors and determinants will be used by health professionals to update clinical guidelines for prevention, screening and early detection of melanoma in CAYA. Health care system strategies will be implemented in European countries overcoming current gaps in European countries on prevention and diagnosis of melanoma in CAYA. The success will be measured by incidence rates of melanoma.	01.06.2025 - 30.09.2026

Collaborators and Investigators

• Sponsor: University Hospital Tuebingen
• Collaborators: Karolinska University Hospital; Hospital Clinic of Barcelona; Fondazione IRCCS Istituto Nazionale dei Tumori, Milano; University Of Perugia; Princess Maxima Center for Pediatric Oncology; Medical University of Gdansk; Leibniz Research Institute for Environmental Medicine Düsseldorf

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2024
• Primary Completion (Estimated): May 31, 2025
• Study Completion (Estimated): May 31, 2026

Study Registration Dates

• First Submitted: September 25, 2024
• First Submitted That Met QC Criteria: November 6, 2024
• First Posted (Estimated): November 8, 2024

Study Record Updates

• Last Update Posted (Estimated): November 8, 2024
• Last Update Submitted That Met QC Criteria: November 6, 2024
• Last Verified: September 1, 2024

More Information

Terms related to this study

• Keywords: children; epidemiology; adolescents; young adults; melanoma; genetic predisposition; etiology; exposomes
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms by Site; Neoplasms; Disease Attributes; Neoplasms by Histologic Type; Skin Diseases; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Neuroendocrine Tumors; Nevi and Melanomas; Skin Neoplasms; Disease Susceptibility; Melanoma; Genetic Predisposition to Disease
• Other Study ID Numbers: 834/2023BO2

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No