The variant enrichment analysis (VEA), a recently developed bioinformatic workflow,
has been shown to be a valuable tool for whole-exome sequencing data analysis, allowing finding
differences between the number of genetic variants in a given pathway compared to a reference
dataset. In a previous study, using VEA, we identified different pathway signatures associated with
the development of pulmonary toxicities in mesothelioma patients treated with radical hemithoracic
radiation therapy. Here, we used VEA to discover novel pathways altered in individuals exposed to
asbestos who developed or not asbestos-related diseases (lung cancer or mesothelioma). A populationbased
autopsy study was designed in which asbestos exposure was evaluated and quantitated by
investigating objective signs of exposure. We selected patients with similar exposure to asbestos.
Formalin-fixed paraffin-embedded (FFPE) tissues were used as a source of DNA and whole-exome
sequencing analysis was performed, running VEA to identify potentially disrupted pathways in
individuals who developed thoracic cancers induced by asbestos exposure. By using VEA analysis,
we confirmed the involvement of pathways considered as the main culprits for asbestos-induced
carcinogenesis: oxidative stress and chromosome instability. Furthermore, we identified protective
genetic assets preserving genome stability and susceptibility assets predisposing to a worst outcome.
