Radon and Lung Cancer: Current Trends and Future Perspectives

SIMPLE SUMMARY: Radon represents the main risk factor of lung cancer in non-smokers and the second one in smoking patients. In Europe, there are several radon-prone areas, but regulatory policies may vary between countries. Radon causes DNA damage and high genomic tumor instability, but its exact carcinogenesis mechanism in lung cancer remains unknown. Molecular drivers in NSCLC are more often described in non-smoker patients and a potential association between radon exposure and oncogenic-driven NSCLC has been postulated. This is an updated review on indoor radon exposure and its role in lung cancer carcinogenesis, especially focusing on its potential relation with NSCLC with driver genomic alterations. We want to contribute to rising knowledge and awareness on this still silent but preventable lung cancer risk factor. ABSTRACT: Lung cancer is a public health problem and the first cause of cancer death worldwide. Radon is a radioactive gas that tends to accumulate inside homes, and it is the second lung cancer risk factor after smoking, and the first one in non-smokers. In Europe, there are several radon-prone areas, and although the 2013/59 EURATOM directive is aimed to regulate indoor radon exposition, regulating measures can vary between countries. Radon emits alpha-ionizing radiation that has been linked to a wide variety of cytotoxic and genotoxic effects; however, the link between lung cancer and radon from the genomic point of view remains poorly described. Driver molecular alterations have been recently identified in non-small lung cancer (NSCLC), such as somatic mutations (EGFR, BRAF, HER2, MET) or chromosomal rearrangements (ALK, ROS1, RET, NTRK), mainly in the non-smoking population, where no risk factor has been identified yet. An association between radon exposure and oncogenic NSCLC in non-smokers has been hypothesised. This paper provides a practical, concise and updated review on the implications of indoor radon in lung cancer carcinogenesis, and especially of its potential relation with NSCLC with driver genomic alterations.