Pre-diagnostic Body Mass Index Trajectories and Associations with Lung Cancer Risk

Mendelian randomization can reveal the etiological association between body mass index (BMI) and lung cancer. However, the associations between the trajectories of BMI and the risk of lung cancer remain inconclusive. We employed growth mixture modeling to identify trajectories of pre-diagnostic BMI in 163,545 individuals (117,445 women from the Nurses’ Health Study and 46,100 men from the Health Professionals Follow-Up Study). We assessed the associations between BMI trajectories and lung cancer risk, as well as the effects within subgroups. Four trajectories were identified: normal-moderate increasing (Class 1), overweight-marked increasing (Class 2), overweight-obese turning (Class 3), and obese-persistent (Class 4). We observed a decreased risk of lung cancer in Class 2 (adjusted hazard ratio [aHR] = 0.53, 95% confidence interval [CI] = 0.38-0.75, P = 2.32×10-4) and Class 3 (aHR = 0.67, 95% CI = 0.48-0.94, P = 0.022). In stratification analysis, we observed that the effects of Class 4 on lung cancer risk vary among histological subtypes. Additionally, within the Class 1 population, the top quintile of BMI also demonstrated different effects among histological subtypes. Increasing lifetime BMI was associated with a decreased risk of lung cancer, with this association varying by histological subtypes, indicating histology-specific mechanisms in lung carcinogenesis.