CHRONIC lung disease and socioeconomic disadvantage were tied to markedly increased lung cancer risk, among never-smokers in Korea.
Lung Cancer Risk in Never-Smokers Linked to Chronic Lung Disease
While lung cancer screening has reduced mortality in high-risk smokers, risk factors for lung cancer in never-smokers remain less clearly defined. In this multicenter, retrospective matched case-control study, investigators examined clinical and environmental contributors to lung cancer in never-smokers (LCINS) using data from tertiary centers in the Republic of Korea.
The analysis included 3,000 never-smoking case patients diagnosed with non-small cell lung cancer (NSCLC) between 2016 and 2020 and 3,000 age- and sex-matched controls. Controls were selected from individuals who underwent opportunistic chest computed tomography (CT) scans with negative findings at the same institutions during the same period. The median age across the cohort was 60 years, and most participants were female (81.1%). Among case patients, Stage I disease was the most common presentation (66.7%).
Adjusted multivariable conditional logistic regression identified chronic lung disease as the strongest independent risk factor for NSCLC in never-smokers (adjusted odds ratio [aOR] 2.91; 95% confidence interval [CI] 2.35–3.59; P<0.001), supporting the concept that underlying respiratory disease may meaningfully increase LCINS risk.
Socioeconomic Status and Family History Influence Risk
Several socioeconomic indicators were also independently associated with NSCLC in never-smokers. Living outside the capital region was linked to higher risk (aOR 2.81; 95% CI 2.49–3.17; P<0.001), and unemployment was associated with increased odds of NSCLC (aOR 1.32; 95% CI 1.14–1.53; P<0.001). In contrast, undergraduate-level or higher education was associated with lower LCINS risk (aOR 0.53; 95% CI 0.44–0.63; P<0.001).
A first-degree family history of lung cancer was associated with a modest increase in NSCLC risk among never-smokers (aOR 1.23; 95% CI 1.02–1.49; P=0.028). Notably, the presence of a first-degree family history was not statistically associated with driver mutations among case patients, suggesting familial risk may not directly align with molecular alteration patterns in this cohort.
Overall, the findings support a multifactorial approach to risk assessment and may help shape future lung cancer screening criteria for higher-risk never-smoker populations.
Reference: Kwak HS et al. Impact of chronic lung disease, socioeconomic status, and family history on lung cancer risk in never-smokers: a matched case-control study. Chest. 2025;doi:10.1016/j.chest.2025.12.003.
