Association of asthma and lung cancer risk: A pool of cohort studies and Mendelian randomization analysis

Background: Over the past 2 decades, population-based studies have shown an increased association between asthma and the risk of lung cancer. However, the causal links between these 2 conditions remain poorly understood. Methods: We conducted a comprehensive search of various databases, including PubMed, Embase, Web of Science, and Cochrane Library, up until May 04, 2023. Only articles published in English were included in our study. We performed a meta-analysis using random-effects models to calculate the odds ratio (OR) and corresponding 95% confidence interval (CI). Subgroup analyses were conducted based on study design, gender, and histologic types. We also conducted a 2-sample Mendelian randomization (MR) using the genome-wide association study pooled data (408,422 people) published by the UK Biobank to explore further the potential causal relationship between asthma and lung cancer. Results: Our meta-analysis reviewed 24 population-based cohort studies involving 1072,502 patients, revealing that asthma is significantly associated with an increased risk of lung cancer (OR = 1.29, 95% CI 1.19–1.38) in all individuals. Subgroup analysis showed a significantly higher risk of lung cancer in females with asthma (OR = 1.23, 95% CI 1.01–1.49). We found no significant association between asthma and lung adenocarcinoma (LUAD) (OR = 0.76, 95% CI 0.54–1.05), lung squamous carcinomas (LUSC) (OR = 1.09, 95% CI 0.79–1.50), or small-cell lung cancer (SCLC) (OR = 1.00, 95% CI 0.68–1.49). Interestingly, our MR analysis supported an increasing causality between asthma and lung cancer (OR = 1.11, 95% CI 1.04–1.17, P = .0008), specifically in those who ever smoker (OR = 1.09, 95% CI 1.01–1.16, P = .0173) and LUSC pathological type (OR = 1.15, 95% CI 1.05–1.26, P = .0038). Conclusion: Through meta-analysis, our study confirms that patients with asthma have a higher risk of developing lung cancer. Our MR study further support an increasing causal relationship between asthma and the risk of lung cancer, particularly in smokers and LUSC. Future studies examining the link between asthma and the risk of developing lung cancer should consider the bias of controlled and uncontrolled asthma.