Abstract
<title>Abstract</title> <p>Background Chronic obstructive pulmonary disease (COPD) is associated with substantial global morbidity and mortality. However, its bidirectional relationship with cancer development and overall survival remains incompletely understood. Methods We analyzed data from 485,480 UK Biobank and 46,597 US NHANES participants. At baseline, participants were classified into four mutually exclusive groups: neither condition, COPD only, cancer only, or both. Logistic regression assessed baseline associations between COPD and prevalent cancer. Kaplan–Meier and Cox proportional hazards models evaluated incident cancer, incident COPD, and all-cause mortality, excluding individuals with the respective condition at baseline. Multivariable models adjusted for sociodemographic, lifestyle, and anthropometric factors. Results At baseline, COPD was associated with higher odds of prevalent cancer in the UK Biobank (OR 1.28, 95% CI 1.23–1.34) and NHANES (OR 1.62, 95% CI 1.42–1.86). In longitudinal analyses, baseline COPD predicted a higher risk of incident cancer (HR 1.18, 95% CI 1.15–1.22), while baseline cancer predicted a higher risk of incident COPD (HR 1.31, 95% CI 1.26–1.36). Coexisting COPD and cancer conferred the highest all-cause mortality risk in both cohorts (UK Biobank: HR 2.94, 95% CI 2.74–3.16; NHANES: HR 2.03, 95% CI 1.76–2.34), compared with those with neither condition. Conclusion COPD and cancer share a robust bidirectional relationship characterized by an increased joint disease burden and substantially poorer survival outcomes. The coexistence of both conditions identifies a highly vulnerable clinical phenotype with a compounded mortality risk, supporting the need for integrated risk assessment and coordinated care.</p>