牙病或增加肺癌风险，尤其鳞癌与肺功能下降有关
Dissecting the Dental Lung Cancer Axis via Mendelian Randomization and Mediation Analysis
- 用遗传数据做因果分析，排除观察偏倚
- 蛀牙每升一个标准差，鳞癌风险高188%
- 肺功能下降解释了约5%的致癌路径，适合预防研究
牙周炎和蛀牙是全球影响数十亿人的常见口腔疾病。尽管观察性研究提示二者与肺癌相关，但因果关系尚不明确。本研究采用两样本孟德尔随机化（MR）方法，探讨蛀牙、牙周炎与肺癌亚型之间的因果关系，并评估肺功能的中介作用。遗传工具来自最大规模全基因组关联研究，涵盖487,823例蛀牙和506,594例牙周炎病例，以及来自肺癌跨学科研究联盟的肺癌数据。主要分析采用逆方差加权法，肺功能中介效应通过delta法评估。结果显示，蛀牙对总体肺癌及其亚型具有显著正向因果效应。具体而言，蛀牙发病率每上升一个标准差，鳞状细胞肺癌风险升高188.0%（OR = 2.880，95% CI = 1.236–6.713，p = 0.014），该效应部分由肺活量（FVC）和第一秒用力呼气量（FEV1）下降介导，分别解释总效应的5.124%和5.890%。牙周炎未发现因果效应。结果表明蛀牙在肺癌发生中具有因果作用，支持将口腔护理与肺功能监测纳入癌症预防策略。
原文摘要 · Abstract (English)
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.
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