Associations between respiratory diseases and lung cancer risk: a secondary analysis of the large-scale prospective UK biobank cohort

INTRODUCTION: Respiratory diseases are significant risk factors for lung cancer; however, the association between acute respiratory infections and lung cancer incidence requires further exploration. METHODS: We performed a secondary analysis of the prospective UK Biobank cohort, including participants aged 37-73 years recruited from 22 assessment centres across the UK between 2006 and 2010. Cox proportional hazards models estimated HRs for incident lung cancer according to respiratory disease status, which was defined based on linked hospital inpatient records. Mediation analysis explored potential biomarkers, and Mendelian randomisation assessed causal relationships. RESULTS: During a mean follow-up of 10.44 years (4 790 738 person-years), 2189 participants developed lung cancer. Among 107 007 individuals with respiratory diseases, 1322 cases occurred (incidence rate 27.6 per 10 000 person-years), compared with 867 cases among 351 876 participants without respiratory diseases (7.9 per 10 000 person-years). Overall, respiratory diseases were associated with increased lung cancer risk (HR 2.97, 95% CI 2.75 to 3.21). Acute respiratory infections, including acute nasopharyngitis (HR 3.41; 95% CI 1.83 to 6.34), influenza (HR 3.90; 95% CI 2.53 to 6.01), viral pneumonia (HR 9.86; 95% CI 6.55 to 14.85) and bacterial pneumonia (HR 6.28; 95% CI 4.40 to 8.96), showed strong associations with lung cancer incidence. In subtype analyses, squamous cell carcinoma exhibited the highest risk elevation (HR 3.65; 95% CI 3.06 to 4.36). Mediation analysis indicated that neutrophil counts partially mediated these associations (proportion mediated up to 8%). CONCLUSION: Acute respiratory infections were associated with higher lung cancer incidence, providing hypothesis-generating evidence that may inform future risk stratification research.