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

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.

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.

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).

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.