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

Recruiting

• Conditions: Melanoma; Spitzoid Melanoma; Congenital Nevi

• Registration Number: NCT06680323
• Lead Sponsor: University Hospital Tuebingen

Brief Summary

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.

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 Timeline

• Study Start: 2024-01-01
• Status Verified: 2024-09
• Study First Submitted: 2024-09-25
• Study First Submitted QC: 2024-11-06
• Last Update Submitted: 2024-11-06
• Study First Posted: 2024-11-08
• Last Update Posted: 2024-11-08
• Primary Completion: 2025-05-31
• Study Completion: 2026-05-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 200

Inclusion Criteria

• confirmed melanoma
• age until 30 years old

Exclusion Criteria

• no available biological material
• no signed informed consent

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Identification of environmental and genetic factors involved in the risk and progression of melanoma in children, adolescents and young adults (CAYA)	01.01.2024 - 30.11.2025	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.

Secondary Outcome Measures

Name	Time	Method
Generating a polygenic risk score for melanoma in CAYA by using the Lindeman-Merenda-Gold (LMG) method	01.06.2024 - 31.05.2026	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.
Prevention strategies for melanoma development in CAYA	01.06.2025 - 30.09.2026	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.

Trial Locations

Locations (6)

Leibniz Research Institute for Environmental Medicine; 🇩🇪 Düsseldorf, Germany

Hospital Clínic de Barcelona; 🇪🇸 Barcelona, Spain

University of Florence; 🇮🇹 Florence, Italy

Karolinska Institute; 🇸🇪 Solna, Sweden

Istituto Nazionale del Tumori; 🇮🇹 Milan, Italy

Medical University of Gdánsk; 🇵🇱 Gdańsk, Poland