Abstract 1375: Cardiorespiratory multimorbidity and lung cancer risk: A population-based cohort study.

Abstract Background: Studies have suggested close links between cardiorespiratory diseases and lung cancer. The coexistence of respiratory disease (RD) and cardiovascular disease (CVD) is common. However, the impact of cardiorespiratory multimorbidity (CRM) and its progression trajectory remains poorly understood. This study aimed to explore the relationship of CRM with lung cancer risk and characterize disease trajectories from healthy state through RD, CVD, or subsequent CRM to lung cancer. Methods: We included 365,735 UK Biobank participants who were free of cancer, RD, or CVD at baseline and had a follow-up time of more than one year. CRM was defined as the co-occurrence of ≥1 RD and ≥1 CVD. RD comprised COPD and asthma. CVD included angina, myocardial infarction (MI), atrial fibrillation (AF), heart failure (HF), peripheral vascular disease (PVD) and stroke. The study outcome was incident lung cancer. Time-varying Cox regression models and accelerated failure time (AFT) regression models were used to assess the associations of CRM with risks of lung cancer incidence and onset time of lung cancer. Multi-state model was further constructed to characterize progression trajectory from healthy state through RD, CVD, or CRM to lung cancer, and to estimate the transition intensity, transition probability and transition time from each state to lung cancer. Results: During a median follow-up of 13.7 years, 3,464 of the 365,735 participants were diagnosed with lung cancer. Cox models showed that CRM was associated with the highest risk of lung cancer incidence (hazard ratio HR=4.11, 95% CI: 3.48-4.85), followed by RD (HR=3.39, 95% CI: 3.01-3.81) and CVD (HR=1.52, 95% CI: 1.36-1.70). AFT models indicated that participants with CRM also showed an earlier onset time of lung cancer (time ratio TR=0.20, 95% CI: 0.17-0.23) than those with RD (TR = 0.25, 95% CI: 0.22-0.28) or CVD (TR = 0.53, 95% CI: 0.48-0.59). The multi-state model showed that 22.0% of participants with RD progressed to CRM, compared with 4.9% of those with CVD. The transition proportion to lung cancer was highest for CRM (2.8%), followed by RD (2.1%) and CVD (0.8%). The transition intensity and transition probability curves revealed that the transition intensity and probability from CRM to lung cancer was greater than that from RD or CVD to lung cancer. Additionally, CRM was associated with a significantly shortened progression time to lung cancer (12.39 years) than RD (12.64 years) or CVD (12.87 years). Conclusion: CRM is associated with a higher lung cancer risk and more rapid progression than individual RD or CVD. These results emphasize CRM may serve as a high-risk clinical phenotype in lung cancer prevention and underscore the potential value of incorporating CRM management into lung cancer prevention strategies. Citation Format: Peng Wang, Yacong Zhang, Han Du, Hongji Dai, Kexin Chen. Cardiorespiratory multimorbidity and lung cancer risk: A population-based cohort study abstract. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 1375.