Zheng Jiazhen, Huang Jinghan, Yang Quan, Zhou Rui, Huang Yining, Wu Xianbo, Tang Shaojun
Bioscience and Biomedical Engineering Thrust (J. Z. and S.T.), Systems Hub, The Hong Kong University of Science and Technology (Guangzhou), Guangzhou, China.
Biomedical Genetics Section (J. H.), School of Medicine, Boston University, Boston, MA; Department of Chemical Pathology (J. H.), Faculty of Medicine, Chinese University of Hong Kong, Hong Kong.
Chest. 2025 Jan;167(1):270-282. doi: 10.1016/j.chest.2024.06.3811. Epub 2024 Jul 29.
Although infections play a role in the development of lung cancer, the longitudinal association between infection and the risk of lung cancer is disputed, and data relating to pathogen types and infection sites are sparse.
How do infections affect subsequent lung cancer risk, and is the impact limited to specific microbes rather than infection burden?
Data on > 900 infectious diseases were gathered from the UK Biobank study. Short- and long-term effects of infections were assessed by using time-varying Cox proportional hazards models. The analysis was repeated, excluding patients with concurrent multi-pathogen infections or outcomes within the 10 years following the initial hospitalization for the index infection. A life table approach was used to estimate years of life lost from lung cancer. Infection burden was defined as the sum of the number of infection episodes over time and co-occurring infections. The genome-wide association studies used in two-sample Mendelian randomization were obtained from mostly European ancestry.
Hospital-treated infectious disease was associated with a greater risk of lung cancer (adjusted hazard ratio [aHR], 1.79; 95% CI, 1.74-1.83). aHRs for lung cancer ranged from 1.39 to 2.82 across pathogen types. The impact of lower respiratory tract infections (LRTIs) on lung cancer was the strongest, with an aHR of 3.22 (95% CI, 2.64-3.92); the aHR for extra-LRTIs was 1.29 (95% CI, 1.16-1.44). A dose-response association was observed between infection burden and lung cancer risk across different FEV percent predicted (P < .001). Multiple infections led to significant life lost from lung cancer at the age of 50 years. Mendelian randomization analysis reaffirmed the causal association.
Both observational and genetic analyses suggest that infectious diseases could increase the risk of lung cancer. The dual perspective on the LRTIs and extra-LRTIs impacts may inform lung cancer prevention strategies.
尽管感染在肺癌发生中起作用，但感染与肺癌风险之间的纵向关联存在争议，且关于病原体类型和感染部位的数据稀少。
感染如何影响后续肺癌风险，其影响是否仅限于特定微生物而非感染负担？
从英国生物银行研究中收集了900多种传染病的数据。采用时变Cox比例风险模型评估感染的短期和长期影响。重复进行分析，排除同时患有多种病原体感染的患者或在首次因索引感染住院后10年内出现结局的患者。采用生命表法估计肺癌导致的寿命损失年数。感染负担定义为随时间的感染发作次数和同时发生的感染次数之和。两样本孟德尔随机化中使用的全基因组关联研究大多来自欧洲血统。
医院治疗的传染病与更高的肺癌风险相关（调整后风险比[aHR]，1.79；95%置信区间，1.74 - 1.83）。不同病原体类型的肺癌aHR范围为1.39至2.82。下呼吸道感染（LRTIs）对肺癌的影响最强，aHR为3.22（95%置信区间，2.64 - 3.92）；LRTIs以外的感染aHR为1.29（95%置信区间，1.16 - 1.44）。在不同预测FEV百分比水平上，观察到感染负担与肺癌风险之间存在剂量反应关联（P <.001）。多次感染导致50岁时因肺癌显著损失寿命年数。孟德尔随机化分析再次证实了因果关联。
观察性和基因分析均表明传染病可能增加肺癌风险。对LRTIs和LRTIs以外感染影响的双重视角可能为肺癌预防策略提供信息。
