Hospital-treated infectious diseases, infection burden and risk of lung cancer: an observational and Mendelian randomisation study

Abstract

BackgroundAlthough 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 is sparse.Research Question:How do infections impact subsequent lung cancer risk and whether the impact is limited to specific microbes rather than infection burden? MethodsWe ascertained 900+ infectious diseases from the UK Biobank study. Short- and long-term effect of infections was assessed using time-varying Cox proportional hazard models. The analysis was repeated, excluding patients with concurrent multi-pathogen infections or outcomes within the ten years after initial hospitalization for the index infection. Life table 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 (GWAS) used in two-sample Mendelian randomization (MR) were obtained from mostly European ancestry. ResultsHospital-treated infectious disease was associated with a greater risk of lung cancer (adjusted HR [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], while the aHR for extra-LRTIs was 1.29 [1.16–1.44]). A dose-response association was observed between infection burden and lung cancer risk across different FEV1% predicted (p-trend <0.001). Multiple infections led to a significant life lost from lung cancer at the age of 50. MR analysis reaffirmed the causal association. InterpretationBoth observational and genetic analyses suggested that infectious diseases could increase the risk of lung cancer. The dual perspective on the LRTIs and extra-LRTIs impacts may inform lung cancer preventive strategies.