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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 population-based 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.<\/jats:p>","DOI":"10.3390\/ijms232113628","type":"journal-article","created":{"date-parts":[[2022,11,7]],"date-time":"2022-11-07T03:14:26Z","timestamp":1667790866000},"page":"13628","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Variant Enrichment Analysis to Explore Pathways Disruption in a Necropsy Series of Asbestos-Exposed Shipyard Workers"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8493-1168","authenticated-orcid":false,"given":"Sergio","family":"Crovella","sequence":"first","affiliation":[{"name":"Biological Sciences Program, Department of Biological and Environmental Sciences, College of Arts and Sciences, University of Qatar, Doha 2713, Qatar"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9112-7167","authenticated-orcid":false,"given":"Ronald Rodrigues","family":"Moura","sequence":"additional","affiliation":[{"name":"Institute for Maternal and Child Health\u2014IRCCS \u201cBurlo Garofolo\u201d, 34137 Trieste, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8588-4559","authenticated-orcid":false,"given":"Lucas","family":"Brand\u00e3o","sequence":"additional","affiliation":[{"name":"Department of Pathology, Center of Medical Sciences, Federal University of Pernambuco, Recife 50670-901, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francesca","family":"Vita","sequence":"additional","affiliation":[{"name":"UCO Anatomia e Istologia Patologica, Azienda Sanitaria Universitaria Giuliano Isontina (ASUGI), Hospital of Cattinara, 34149 Trieste, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Manuela","family":"Schneider","sequence":"additional","affiliation":[{"name":"UCO Anatomia e Istologia Patologica, Azienda Sanitaria Universitaria Giuliano Isontina (ASUGI), Hospital of Cattinara, 34149 Trieste, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fabrizio","family":"Zanconati","sequence":"additional","affiliation":[{"name":"UCO Anatomia e Istologia Patologica, Azienda Sanitaria Universitaria Giuliano Isontina (ASUGI), Hospital of Cattinara, 34149 Trieste, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luigi","family":"Finotto","sequence":"additional","affiliation":[{"name":"Occupational Health Unit, Local Health Authority, 34074 Monfalcone, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paola","family":"Zacchi","sequence":"additional","affiliation":[{"name":"Department of Life Sciences, University of Trieste, 34127 Trieste, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giuliano","family":"Zabucchi","sequence":"additional","affiliation":[{"name":"Department of Life Sciences, University of Trieste, 34127 Trieste, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Violetta","family":"Borelli","sequence":"additional","affiliation":[{"name":"Department of Life Sciences, University of Trieste, 34127 Trieste, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,11,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1080\/10937404.2016.1193361","article-title":"Five years update on relationships between malignant pleural mesothelioma and exposure to asbestos and other elongated mineral particles","volume":"19","author":"Andujar","year":"2016","journal-title":"J. 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