Naidu, Sindhu Bhaarrati;
Wisking, Allegra;
Karoshi, Akul;
Burdett, Sarah;
Godolphin, Peter J;
Popat, Sanjay;
Janes, Sam M;
(2025)
Risk Factors Associated With Incidence of Lung Cancer in Never-Smokers: A Systematic Review and Meta-Analysis.
JTO Clinical and Research Reports
, 6
(12)
, Article 100910. 10.1016/j.jtocrr.2025.100910.
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Abstract
OBJECTIVE: Lung cancer is the leading cause of cancer mortality globally. Although often associated with smoking, up to 25% of cases worldwide and 50% in East Asia occur in “never-smokers.” There are currently no robust tools for predicting lung cancer in individuals who have never smoked (LCINS) for populations outside East Asia. Together with a group of patient representatives, the authors of this study aimed to summarise risk factors for LCINS and quantify risk in different geographical regions. METHODS: This study was prospectively registered (PROSPERO-CRD42022379253). The systematic review and meta-analysis included studies published from 2017 and aimed to comprehensively investigate risk factors associated with LCINS incidence. Risk of bias was assessed using Newcastle-Ottawa Scale. RESULTS: A total of 6725 reports were identified and 54 studies were included, with multivariable analysis of 192 factors in 16 million never-smokers. No studies were assessed as having high risk of bias. Of the participants, 8,241,269 (51.0%) were from Western countries. The meta-analysis found that female sex (adjusted hazard ratio [aHR] 1.28 [95% confidence interval or CI 1.12–1.47]), previous cancer (aHR 2.04 [1.95–2.13]), rheumatoid arthritis (aHR 1.41 [1.15–1.73]), passive smoking (aHR 1.30 [1.22–1.40]), PM10 (aHR 1.10 [1.09–1.11]), and PM2.5 (aHR 1.16 [1.03–1.30]) pollution were associated with LCINS. In planned subgroup analyses by region, LCINS was associated with family history of lung cancer in East Asian (aHR 1.56 [1.23–1.98]) but not Western countries (aHR 0.86 [0.35–2.11]). CONCLUSION: We found key factors linked with LCINS, including female sex, rheumatoid arthritis, and pollution and, for the first time, quantified their association through meta-analyses of studies globally. This may be used to develop tools to detect LCINS earlier.
| Type: | Article |
|---|---|
| Title: | Risk Factors Associated With Incidence of Lung Cancer in Never-Smokers: A Systematic Review and Meta-Analysis |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1016/j.jtocrr.2025.100910 |
| Publisher version: | https://doi.org/10.1016/j.jtocrr.2025.100910 |
| Language: | English |
| Additional information: | © 2025 The Authors. Published by Elsevier Inc. on behalf of the International Association for the Study of Lung Cancer. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). |
| Keywords: | Lung neoplasms, Never-smokers, Nonsmokers, Risk factors, Epidemiology |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Inst of Clinical Trials and Methodology UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Inst of Clinical Trials and Methodology > MRC Clinical Trials Unit at UCL |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10217132 |
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