Comparative analysis of lung cancer risk factors between never-smokers and heavy smokers: a nationwide population-based study in Korea.

Background: Tobacco smoking is a major risk factor for lung cancer; however, more than one-third of newly diagnosed lung cancer cases in Korea occur in never-smokers. Among heavy smokers, the specific characteristics contributing to increased lung cancer risk remain unclear. We investigated the risk factors for lung cancer in never-smokers and in heavy smokers with ≥30 pack-years. Methods: We screened individuals who underwent the national health examination in 2012. We identified two groups: (I) 2,650,867 never-smokers and (II) 269,320 heavy smokers (≥30 pack-years) and followed them until December 2022. Newly diagnosed lung cancer cases were identified as follows: (I) 16,540 among never-smokers and (II) 9,895 among heavy smokers. Multivariable Cox proportional hazards models were applied to determine factors associated with lung cancer in each population. Results: Compared with never-smokers, heavy smokers had approximately fivefold higher lung cancer incidence rates. Lung cancer risk increased with older age, male sex, lower income, alcohol intake, smoking status (current smoking) and cumulative exposure (increasing pack-years), diabetes, history of tuberculosis (TB), and chronic obstructive pulmonary disease (COPD). A history of TB and COPD was associated with nearly twofold higher lung cancer risk. In contrast, body mass index was inversely associated with lung cancer risk. Most risk factors were more pronounced in younger (<65 years) and male populations. Conclusions: Sociodemographic factors, lifestyle behaviors, and comorbidities significantly influence lung cancer risk in both never-smokers and heavy smokers. Current smokers with high cumulative exposure were at greatest risk. TB history and COPD should be incorporated into future lung cancer risk prediction strategies.