Mendelian Randomization Identifies Two Immune Cell Traits Associated with Lung Cancer

Background: Experimental evidence has linked immune cells to lung cancer. It is unclear whether associations for immune cell traits are causal or due to bias. To explore the causal impact of immune cells on lung cancer risk, we conducted a two-sample Mendelian randomization (MR) analysis. Materials and Methods We analyzed the relationship between immune cell traits and lung cancer using a two-sample MR approach. Genome-wide association study (GWAS) summary statistics for 731 immune cell traits and lung cancer risk were assessed. The immune cell characteristics included four types: absolute cell (AC) counts, median fluorescence intensities (MFIs) of surface antigens, morphological parameters (MP) and relative cell (RC) counts. GWAS associated with lung cancer was extracted from a large-scale association analysis that included 29,266 cases and 56,450 controls. Inverse Variance Weighted (IVW) was performed as the primary MR analysis method. Multiple sensitivity analyses are used to evaluate the robustness of the results. Finally, a reverse MR analysis was conducted to assess the possibility of reverse causation. Results MR analysis showed that CD14- CD16 + monocyte %monocyte(OR = 0.924; 95%CI,0.889–0.960) and CD4 on naive CD4+(0.922, 0.889–0.956) was associated with overall lung cancer after accounting for multiple testing. There was no statistically significant effect of immunophenotypes for lung cancer subtypes. Conclusions Our findings suggest that CD14- CD16 + monocyte %monocyte and CD4 on naive CD4 + might protect against lung cancer, and larger-scale genetic data are expected to further validate our findings.