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

Abstract

Abstract Background Over the past two decades, population-based studies have shown an increased association between asthma and the risk of lung cancer. However, the causal links between these two conditions remain poorly understood. Methods We conducted a comprehensive search of various databases, including PubMed, Embase, Web of Science, and Cochrane Library, up until October 01, 2022. 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 two-sample Mendelian randomization (MR) using published genome-wide association study summary data from UK Biobank (376,358 individuals), FinnGen (213,293 individuals), and TAGC (127,669 individuals). We used the fixed effects meta-analysis method to combine estimates from various databases. We used inverse variance weighting (IVW) for the meta-analysis to determine the odds ratio (OR) and corresponding 95% CI. Results Our meta-analysis reviewed 21 population-based cohort studies involving 712,418 patients, revealing that asthma is significantly associated with an increased risk of lung cancer (OR = 1.29, 95% CI 1.19–1.40) 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). However, our MR meta-analysis supported a decreasing causality between asthma and lung cancer (OR = 0.94, 95% CI 0.91–0.98, P = 0.001), specifically with a decreased risk of LUSC (OR = 0.87, 95% CI 0.82–0.92, P < 0.0001). Conclusions Through meta-analysis, our study confirms that patients with asthma have a higher risk of developing lung cancer. Our MR study, however, discovered evidence suggesting a declining causal relationship between asthma and the risk of lung cancer, particularly in LUSC. Future studies examining the link between asthma and the risk of developing lung cancer should consider the bias of controlled and uncontrolled asthma.