Effect Modification by Cofactors in the Impact of Body Mass Index Change on the Risk of Lung Cancer

While baseline body mass index (BMI) has been inversely associated with lung cancer risk, the impact of BMI change remains unclear. Furthermore, stratified analysis by menopausal status and age has not been explored. Cancer-free participants who completed National Health Examinations in 2010 and again in 2014 were included (n = 3,822,171; follow-up through 2021). BMI was measured at both time points, and changes were categorized. We modeled competing-risk outcomes using the Fine-Gray approach to obtain adjusted hazard ratios (aHRs) and 95% confidence intervals (95% CI). During follow-up, 43,704 lung cancer cases occurred. Persistent obesity (obesity I [25.0-29.9 kg/m²], aHR 0.93, 95% CI 0.89-0.97; persistent obesity II [≥ 30.0 kg/m²]: aHR 0.80, 95% CI 0.72-0.90) and transitioning from normal BMI to obesity (aHR 0.79, 95% CI 0.63-0.99) were associated with reduced lung cancer risk. Stratified analyses revealed stronger associations among men and ever smokers. Persistent obesity and BMI gain were associated with reduced risk in both men and women, whereas persistent underweight (aHR 1.24; 95% CI 1.14-1.35) and transitioning from normal BMI to underweight (aHR 1.27; 95% CI 1.17-1.39) were associated with increased risk only in men. Persistent obesity and BMI gain were associated with lower lung cancer risk in never-smokers as well as smokers, but persistent underweight (aHR 1.34, 95% CI 1.22-1.47) elevated lung cancer risk only in smokers. Age and menopausal status further modified the associations. Persistent obesity and BMI gain were protective, whereas underweight and BMI loss elevated lung cancer risk in men and smokers. Registry and the Registration no: NA.