Assessment of Lung Cancer Risks Related to Family History in Never-Smokers: A Cohort Study.

Background: Lung cancer in never-smokers is an increasing issue, particularly in East Asia, where nonsmoking-related risk factors, such as genetic predispositions, play a crucial role. This study investigated the association of family history of lung cancer (FHLC) with lung cancer risk among never-smokers and identified when these risks increased.

Methods: This prospective cohort study used data from the Kangbuk Samsung Cohort Study, which involved 357,322 Korean adults who underwent health screenings from 2011 to 2021. The 167,883 with a history of smoking or previous cancer diagnoses were excluded from this study. FHLC was evaluated through questionnaires, and incident lung cancer cases were determined through the Korea National Cancer Incidence Database.

Results: Of the 189,439 study population, 11,678 reported FHLC. Incident lung cancer was observed in 25 (0.21%) participants with FHLC and 148 (0.083%) without FHLC, yielding an unadjusted hazard ratio (HR) of 1.76 (95% confidence interval [CI]: 1.15-2.69, P = .009). FHLC remained a significant risk factor after adjusting for sex, body mass index, alcohol consumption, exercise, and medical history (HR: 1.93, 95% CI: 1.24-3.01, P = .004). The risk of incident lung cancer based on FHLC significantly diverged after 45 years of age. Propensity score matching confirmed a higher lung cancer risk in nonsmokers with FHLC compared with those without FHLC.

Conclusions: Never-smokers with FHLC demonstrated a significantly higher risk of developing lung cancer, which risks start to increase after 45 years of age. Integrating FHLC into lung cancer screening models has the potential to enhance early detection.