Project results are expected to contribute to some of the following expected outcomes:

• Researchers and health professionals will advance our understanding on how environmental, genetic and epigenetic, omics and other factors interact in determining the onset and development of cancers in children, adolescents and young adults and how they impact health outcomes in young cancer patients.
• Policymakers and public health authorities have scientific evidence to improve prevention strategies to minimise the impacts of environmental factors on the development and progression of paediatric, adolescent and young adult cancers.
• Researchers, innovators, and professionals from across different disciplines and sectors will support and contribute to the future UNCAN.eu research data platform by ensuring interoperability of data, new digital tools and models.

This topic contributes to the Cancer Mission objectives by improving the understanding of the impact of environmental exposures^[1] including, their interaction with other relevant factors on cancer onset^[2] and progression and/or other relevant health outcomes along the cancer patient journey. The age group of interest for this topic includes children, adolescents and young adults (less than 40 years of age at first cancer diagnosis).

Applicants should take advantage of technological advances which have opened up new opportunities to collect, combine and analyse large datasets of diverse types, offering new possibilities to design epidemiological studies to understand the mechanistic contribution of environmental factors, in combination with other individual and contextual factors^[3] as appropriate. Innovative and data intensive approaches are expected for the identification of time windows of susceptibility^[4] and of robust biomarkers of cumulative environmental exposure.

Proposals may envisage the creation of large cohort(s) by pooling and integrating existing retrospective studies in the areas of clinical research, exposome research, cancer registries and complementing with the new collection of other relevant data where needed (other omics data, digital pathology, behavioural and socio-economic data, clinical records etc.). Sex and gender differences should be duly considered. The use of causal interference, computational modelling and/or artificial intelligence tools are encouraged for the analysis and management of big, complex and heterogeneous data sets. All datasets produced should be described with metadata records in the EU dataset catalogue of the future European Health Data Space^[5] while all tools and models should follow the principles of open science and be made available through the future UNCAN.eu platform.

The applicants should address several of the following activities:

• Identify, validate and document different types (and/or combinations) of biomarkers for the development of robust quantitative measures of the effects of cumulative environmental exposures associated with cancer onset;
• Elaborate and test cost effective approaches for measuring biomarkers of cumulative environmental exposure in large paediatric, adolescent and young adult populations, also by applying new analytical tools and novel methods of analysis;
• Identify individual signatures (e.g. based on genetic, epigenetic, multi-omic characteristics), and time windows conferring susceptibility to environmental hazards associated with cancer onset and progression in children, adolescent and young adults at different stages of the life course;
• Identify clinical states, lifestyle and socio-economic factors and circumstances that increase the risk of adverse health outcomes associated with exposure to environmental hazards in different time windows in young cancer patients;
• Develop new tools and methods to combine and analyse multimodal data, including the application of novel data-intensive methods of analysis, while ensuring interoperability with the future UNCAN.eu research platform and taking advantage of current European research infrastructures.

Advantage should be taken to the extent possible of data and experience gained under current large-scale initiatives such as: the European Human Exposome Network (EHEN)^[6], the European Partnership for the Assessment of Risks from Chemicals (PARC)^[7], the clusters of projects under the environment, climate and health research portfolio^[8] and the projects under the 'Understanding' project cluster of the Cancer Mission^[9]. The relevant EU research and health infrastructures should be exploited for available digital tools and services for dataset creation, standardisation, data discovery, secure access, management, visualization, harmonization, analysis and other functions as appropriate. Successful proposals are expected to establish appropriate collaborations with HORIZON-MISS-2024-CANCER-01-01 'Use cases for the UNCAN.eu research data platform'.

The Commission will facilitate coordination with other EU initiatives. Proposals should include a budget for networking, attendance at meetings and joint activities^[10] of the 'Understanding' project cluster of the Cancer Mission^[11].

Proposals should consider the involvement of the European Commission's JRC regarding its experience in this field and with respect to the value it could bring in providing an effective interface between research activities and pre-normative science as well as strategies and frameworks that address regulatory requirements. In that respect, the JRC will consider collaborating with any successful proposal and this collaboration, when relevant, should be established after the proposal’s approval.

Applicants envisaging to include clinical studies should provide details in the dedicated annex using the template provided in the submission system.

[1] The exposure to potentially harmful chemical, physical or biological agents in the environment

[2] Including early onset cancer

[3] Examples are genetic, epigenetic and -omic characteristics, lifestyle, socio-economic factors, clinical status and clinical circumstances

[4] In utero exposures might be included if relevant

[5] https://healthdcat-ap.github.io/

[6] https://www.humanexposome.eu/

[7] https://www.eu-parc.eu/

[8] https://research-and-innovation.ec.europa.eu/research-area/health/environment-and-health_en

[9] https://research-and-innovation.ec.europa.eu/funding/funding-opportunities/funding-programmes-and-open-calls/horizon-europe/eu-missions-horizon-europe/eu-mission-cancer/implementation-page/cancer-mission-objectives_en#understanding-of-cancer.

[10] Examples of these activities are research or research capacity, organising joint workshops, establishing best practices, joint communication or citizen engagement activities with projects funded under other clusters and pillars of Horizon Europe, or other EU programmes, as appropriate. Proposals are not required to include details of these activities, as they will be defined during the grant agreement preparation and during the life of the project.

[11] In order to address the objectives of the Cancer Mission, participants will collaborate in project clusters to leverage EU-funding, increase networking across sectors and disciplines, and establish a portfolio of Cancer Mission R&I and policy actions.