Dissecting the Dental Lung Cancer Axis via Mendelian Randomization and Mediation Analysis

Periodontitis and dental caries are common oral diseases affecting billions globally. While observational studies suggest links between these conditions and lung cancer, causality remains uncertain. This study used two sample Mendelian randomization (MR) to explore causal relationships between dental traits (periodontitis, dental caries) and lung cancer subtypes, and to assess mediation by pulmonary function. Genetic instruments were derived from the largest available genome wide association studies, including data from 487,823 dental caries and 506,594 periodontitis cases, as well as lung cancer data from the Transdisciplinary Research of Cancer in Lung consortium. Inverse variance weighting was the main analytical method; lung function mediation was assessed using the delta method. The results showed a significant positive causal effect of dental caries on overall lung cancer and its subtypes. Specifically, a one standard deviation increase in dental caries incidence was associated with a 188.0% higher risk of squamous cell lung carcinoma (OR = 2.880, 95% CI = 1.236--6.713, p = 0.014), partially mediated by declines in forced vital capacity (FVC) and forced expiratory volume in one second (FEV1), accounting for 5.124% and 5.890% of the total effect. No causal effect was found for periodontitis. These findings highlight a causal role of dental caries in lung cancer risk and support integrating dental care and pulmonary function monitoring into cancer prevention strategies.