Deciphering the Exposome by Metabolomic Technology in Breast Cancer

Projektinformationen

EXPOMET

ID Finanzhilfevereinbarung: 101043321

DOI

10.3030/101043321

EK-Unterschriftsdatum 23 Juni 2022

Startdatum 1 März 2023

Enddatum 29 Februar 2028

Finanziert unter

• European Research Council (ERC)

Gesamtkosten

€ 2 937 489,00

EU-Beitrag

€ 2 937 489,00

Koordiniert durch

UNIVERSITAT WIEN
Austria

Periodic Reporting for period 1 - EXPOMET (Deciphering the Exposome by Metabolomic Technology in Breast Cancer)

Berichtszeitraum: 2023-03-01 bis 2025-08-31

Zusammenfassung vom Kontext und den Gesamtzielen des Projekts

EXPOMET: Transforming Our Understanding of Environmental Contaminants and Breast Cancer

Chronic diseases are on the rise, particularly as our population ages. However, the environmental factors that influence disease risk remain poorly understood. People are exposed to countless chemicals every day, making it extremely difficult to measure these exposures and even harder to uncover how they disrupt biological processes and may cause disease. To tackle this challenge, the concept of the exposome, i.e. the totality of chemical exposures over a lifetime and their biological effects, was proposed. Progress in this field, however, has been slowed down by a lack of suitable analytical technologies.

The EXPOMET project aims to develop innovative analytical tools to advance the emerging field of exposome research, with a particular focus on breast cancer risk and endocrine disruption. The work will involve the development of novel mass spectrometry-based methods and bioinformatic solutions, to process the mass spectrometric data and integrate it with other omics datasets. This integration will facilitate systems toxicology analyses, providing a more comprehensive understanding of environmental influences on health. The newly established global workflows will be applied in an exposome-wide association study (ExWAS) focused on breast cancer. Using data from the ORDET cohort, the study seeks to systematically evaluate environmental exposures as risk factors for the disease. In addition, the project will investigate the functional impact of real-life exposures identified through the ExWAS. Using cell models, researchers will apply metabolomic-guided systems toxicology approaches to examine the metabolic effects of complex chemical mixtures.

Arbeit, die ab Beginn des Projekts bis zum Ende des durch den Bericht erfassten Berichtszeitraums geleistet wurde, und die wichtigsten bis dahin erzielten Ergebnisse

EXPOMET is dedicated to developing advanced high-throughput technologies to comprehensively map the exposome and better understand its role in the development of breast cancer—the most common cancer among European women, affecting one in eight. The project has created innovative targeted and non-targeted analytical workflows that enable scientists to detect and monitor a wide range of environmentally relevant chemicals with unprecedented efficiency. Notably, EXPOMET has established a highly sensitive targeted multi-toxicant assay capable of quantifying over 200 chemicals at extremely low levels in human blood and urine. In addition, a new method has been developed that combines the high sensitivity of targeted mass spectrometry with the broad screening capabilities of non-targeted metabolomics. These cutting-edge approaches have already been successfully tested in initial pilot studies and will now be applied in the next stage of EXPOMET: the first large-scale exposome-wide association study (ExWAS) on breast cancer, using multiple complementary analytical assays.

Fortschritte, die über den aktuellen Stand der Technik hinausgehen und voraussichtliche potenzielle Auswirkungen (einschließlich der bis dato erzielten sozioökonomischen Auswirkungen und weiter gefassten gesellschaftlichen Auswirkungen des Projekts)

The technology developed through EXPOMET will make it possible to routinely conduct exposome-wide association studies (ExWAS) in large-scale epidemiological research, extending far beyond breast cancer—the focus of the project. In principle, this new analytical pipeline can be applied to investigate environmental factors linked to disease risk in any condition influenced by non-genetic causes. By simultaneously measuring both chemical exposures and their biological effects, EXPOMET offers a unique opportunity not only to establish connections between exposures and diseases but also to identify disrupted metabolic pathways and underlying mechanisms of action.

In its next phase, EXPOMET will provide critical insights into how environmental chemicals contribute to cancer development by combining advanced metabolomic techniques with innovative activity-screening tools. Ultimately, the project will deliver breakthrough technology and new knowledge about the relationship between chemical exposures and breast cancer, fundamentally reshaping our understanding of how environmental contaminants impact human health. Based on the findings, it may become necessary to adapt current regulatory frameworks for consumer products and food contaminants to better support disease prevention.

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