Relationship between lung function and lung cancer risk: a pooled analysis of cohorts plus Mendelian randomization study

Background Since little consensus has been reached on whether milder reduction in forced expiratory volume in 1 s (FEV1) increases lung cancer incidence, we conducted a meta-analysis and performed Mendelian randomization (MR) analysis to explore the association and causal relationship between FEV1 and lung cancer incidence. Methods We conducted a comprehensive search from PubMed, Medline, EMBASE, and Cochrane Library databases as of February 2020. MR analysis was performed using summary data obtained from two large consortia [International Lung Cancer Consortium (ILCCO) and Neale Lab] to assess the possible causality between FEV1 and lung cancer risk. Results Eight studies involving 88,743 cases were included. The incidence of lung cancer increased with decreasing FEV1.The combined odds ratio (OR) of decreased FEV1 for lung cancer incidence was 1.91 [95% confidence interval (CI) 1.67-2.19; P < 0.001]. Compared with the highest quintile of FEV1 (quintile 5, > 100% of predicted), the OR was 3.06 (95% CI 2.20-4.24; P < 0.001) for quintile 1 (< 70% of predicted), 1.89 (95% CI 1.50-2.38; P < 0.001) for quintile 2 (70-80% of predicted), 1.53 (95% CI 1.31-1.79; P < 0.001) for quintile 3 (80-90% of predicted), and 1.64 (95% CI 1.18-2.28; P = 0.003) for quintile 4 (90-100% of predicted). In subgroup meta-analysis, the correlation between FEV1 and lung cancer risk was different among men (OR = 1.74; 95% CI 1.49-2.03; P < 0.001) and women (OR = 2.80; 95% CI 1.87-4.19; P < 0.001). However, MR analysis showed no causality between the FEV1 and lung cancer risk (OR = 1.199; 95% CI 0.958-1.500; P = 0.114). Conclusion FEV1 is likely to be a predictor of lung cancer, especially for women. However, genetically decreased FEV1 is not causally correlated with lung cancer incidence.