LUCIA · Understanding Lung Cancer related risk factors and their Impact

Lung Cancer (LC) is the biggest cancer killer worldwide, with five-year survival following diagnosis varying between 5% to 25%. Though tobacco smoking has long been recognized as the major risk factor for LC, many cases (incl. LC patients that are non-smokers) cannot be explained by this reason. In this sense, LUCIA aims to establish a novel toolbox for discovering and understanding new risk factors that contribute to LC development. The toolbox encompasses the analysis of three aspects: (i) personal risk factors, which include a person’s exposure to chemical pollutants and behavioural and lifestyle factors; (ii) external risk factors, such as urban, built and transport environments, social aspects and climate; and (iii) biological responses to the personal and external risk factors, including changes in genetics, epigenetics, metabolism and aging. Key components of the toolbox for analysing personal and external risk factors include retrospective and prospective cohort databases, AI models, wearable devices, novel non-invasive sensors, and multi-omics. Together, these tools will be used to identify the effects of a wide range of environmental, biological, demographic, community and individual-level risk factors associated with the formation of LC. Molecular changes associated with the risk factors identified by this set of tools will then be validated by cell and molecular biology methods and through in vivo analysis. The impact of the identified personal and external risk factors and the associated biological responses will be then validated in three clinical use cases: general population risk assessment and screening, precision screening of high-risk populations, and digital diagnostics. The resulting evidence within LUCIA will be translated into policymaking recommendations, with the aim to implement them in a screening program for LC. This action is part of the Cancer Mission cluster of projects on ‘Understanding'.