Risk Factors Associated With Incidence of Lung Cancer in Never-Smokers: A Systematic Review and Meta-Analysis
Abstract
Objectives 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…
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