{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T21:50:38Z","timestamp":1791841838753,"version":"4.3.4"},"reference-count":43,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2025,9,13]],"date-time":"2025-09-13T00:00:00Z","timestamp":1757721600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Background\/Objectives: Lung cancer (LC) remains one of the most lethal malignancies worldwide, with both environmental and occupational exposures contributing to its incidence. While oncogene-addicted tumors\u2014defined by single driver mutations\u2014have garnered attention due to their therapeutic implications, less is known about the mutational landscape of tumors potentially arising from occupational exposure to carcinogens. This real-life observational study aimed to assess whether previous occupational exposure to lung carcinogens correlates with distinct LC phenotypes, particularly non-oncogene-addicted (nOA) profiles. Methods: A total of 199 LC patients were enrolled across two specialized oncology centers in Northern Italy between 2021 and 2023. Each participant underwent detailed occupational history taking and molecular characterization using next-generation sequencing. Patients were stratified into nonexposed (NE), low exposed (LE), and high exposed (HE) to carcinogens for lung based on standardized questionnaires and sector-specific assessments. Results: No significant differences were found in histological subtypes across exposure groups. However, people with adenocarcinoma and high occupational exposure to lung carcinogens were more frequently characterized by a nOA phenotype compared to those with low occupational exposure. Logistic regression models\u2014adjusted for age, sex, and smoking habits\u2014confirmed that HE patients had a significantly higher likelihood of developing nOA tumors (OR = 3.07; 95% CI: 1.16\u20138.11; p = 0.023). This association persisted after adjusting for smoking habits Exposures occurring 5\u201310 years before diagnosis seemed to be associated with an increased nOA profile. Conclusions: These findings suggest that high levels of exposure to occupational carcinogens impact LC phenotypes. Indeed, these phenotypes are more complex to treat and show the worst prognosis. Assessing the occupational exposure to lung carcinogens during work may offer prognostic insights and support the request for more adequate compensation for the patients. Further studies are warranted to validate these results and to explain the mechanisms that produce the differences observed in LC phenotypes in people with high exposure to occupational carcinogens.<\/jats:p>","DOI":"10.3390\/cancers17182997","type":"journal-article","created":{"date-parts":[[2025,9,15]],"date-time":"2025-09-15T09:43:41Z","timestamp":1757929421000},"page":"2997","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Exposure to Occupational Carcinogens and Non-Oncogene Addicted Phenotype in Lung Cancer: Results from a Real-Life Observational Study"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8503-6560","authenticated-orcid":false,"given":"Enrico","family":"Oddone","sequence":"first","affiliation":[{"name":"Department of Public Health, Experimental and Forensic Medicine, University of Pavia, 27100 Pavia, Italy"},{"name":"Hospital Occupational Medicine Unit (UOOML), ICS Maugeri IRCCS, 27100 Pavia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luca","family":"D\u2019Amato","sequence":"additional","affiliation":[{"name":"Department of Public Health, Experimental and Forensic Medicine, University of Pavia, 27100 Pavia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5925-1352","authenticated-orcid":false,"given":"Roberta","family":"Pernetti","sequence":"additional","affiliation":[{"name":"Department of Public Health, Experimental and Forensic Medicine, University of Pavia, 27100 Pavia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Domenico","family":"Madeo","sequence":"additional","affiliation":[{"name":"Hospital Occupational Medicine Unit (UOOML), ICS Maugeri IRCCS, 27100 Pavia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4023-7542","authenticated-orcid":false,"given":"Luca","family":"Toschi","sequence":"additional","affiliation":[{"name":"IRCCS Humanitas Research Hospital, Cancer Center, Rozzano, 20089 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Farinatti","sequence":"additional","affiliation":[{"name":"IRCCS Humanitas Research Hospital, Cancer Center, Rozzano, 20089 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giulia","family":"Riva","sequence":"additional","affiliation":[{"name":"Medical Oncology Unit, ICS Maugeri IRCCS, 27100 Pavia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucrezia","family":"Spina","sequence":"additional","affiliation":[{"name":"Medical Oncology Unit, ICS Maugeri IRCCS, 27100 Pavia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-9305-1006","authenticated-orcid":false,"given":"Luigia","family":"Ferrante","sequence":"additional","affiliation":[{"name":"International Medical School, Humanitas University, Pieve Emanuele, 20072 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-1582-9329","authenticated-orcid":false,"given":"Catharina","family":"Conde","sequence":"additional","affiliation":[{"name":"International Medical School, Humanitas University, Pieve Emanuele, 20072 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3315-2580","authenticated-orcid":false,"given":"Laura Deborah","family":"Locati","sequence":"additional","affiliation":[{"name":"Medical Oncology Unit, ICS Maugeri IRCCS, 27100 Pavia, Italy"},{"name":"Department of Internal Medicine and Medical Therapy, University of Pavia, 27100 Pavia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Federico","family":"Sottotetti","sequence":"additional","affiliation":[{"name":"Medical Oncology Unit, ICS Maugeri IRCCS, 27100 Pavia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8283-1988","authenticated-orcid":false,"given":"Franca","family":"Barbic","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, 20072 Milan, Italy"},{"name":"IRCCS Humanitas Research Hospital, Rozzano, 20089 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,9,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2100","DOI":"10.1016\/S0140-6736(24)00367-2","article-title":"Global Burden of 288 Causes of Death and Life Expectancy Decomposition in 204 Countries and Territories and 811 Subnational Locations, 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