The causal association between neutrophil counts and the risk of lung cancer: a Mendelian randomization study

An increased neutrophil level in the blood is considered a risk factor for lung cancer (LC). However, establishment of causality is hampered by the inconsistent findings of observational studies. This study aimed to explore the causal association between neutrophil counts (NC) and LC risk in two populations via two-sample mendelian randomization (MR) analysis. The inverse-variance weighted method was used to evaluate causality. Sensitivity analyses were conducted to examine the stability of the results. Bidirectional MR analysis was performed to check reverse causality, and a multivariable MR analysis was conducted to adjust for confounding factors. The results revealed a significant causal relationship between NC and LC (OR=1.027, 95% CI: 1.005-1.050, P=0.017) in the European population but not in the East Asian population (OR=1.223, 95% CI: 0.999-1.497; P=0.052). The sensitivity analysis confirmed the robustness of the results, and we excluded potential reverse causation. A multivariable analysis demonstrated that a significant genetic association (OR=1.044, 95% CI: 1.002-1.088, P=0.042) remained after controlling for smoking. Our findings provide information on the causal relationship between NC and LC, and highlight the objective differences in genetic variation among ethnicities.