Genetically predicted 15 circulating blood cell traits and Esophageal Cancer：a comprehensive Mendelian randomization study

Background : Epidemiologic evidence indicates that circulating blood cell traits may be linked to both the incidence and outcome of Esophageal Cancer. Nevertheless, these studies are at risk of being influenced by confounding factors. In our research, we conducted Mendelian randomization to explore the potential causal association between circulating blood cell traits and EC. Methods : This study utilized genome-wide association studies (GWAS) datasets to analyze genetic variation using a two-sample MR design. The EC data was obtained from a GWAS study involving 740 cases and 372,016 controls (identifier: ieu-b-4960), while data for 15 circulating blood cell traits were sourced from a GWAS with 562,132 participants. Various statistical methods including Inverse variance weighted (IVW), Weighted median, MR Egger regression, Weighted mode, and Simple mode were employed to assess the causal connection between the circulating blood cell traits and EC. Additionally, a series of sensitivity analyses were conducted to ensure the robustness of the findings. Results : The results found significant association between elevated circulating BAS counts (odds ratio, OR: 1.0012, 95 % confidence interval, CI: 1.0004-1.0020, p =0.0037), and decreased circulating levels of HBG (OR: 0.9994, 95% CI: 0.9989-1.0000, p =0.0403) with the risk of EC in the IVW approach. In addition,circulating blood cell traits including MPV (OR: 0.0506, 95% CI:0.0034 -0.7435, p =0.0295 ) and LYM (OR: 0.1356, 95% CI:0.0209-0.8816, p =0.0364) are suggested to be the consequences of EC Conclusions : In this research, we systematically examined the association between the 15 circulating blood cell traits and the occurrence of EC. We identified upstream regulators (BAS counts) and downstream effectors (HBG concentration) associated with EC. In addition, EC affects circulating levels of LYM counts and MPV. Our results provide valuable insights into the role of circulating blood cell traits in the development of EC, offering new avenues for further research and potential interventions in the prevention and management of EC.