The Causal Relationship Between White Blood Cells Counts and Hepatocellular Carcinoma: A Mendelian Randomization Study

Abstract Background Studies have reported that 90% of hepatocellular carcinoma (HCC) arise and progress on the background of chronic inflammation. The presence of infiltrating inflammatory cells is associated with tumor initiation, progression and clinical response to treatment. Whether white blood cells (WBC) subtypes counts increase or decrease the occurrence of HCC remains unclear. Methods In this study, we made a Mendelian randomization (MR) study with the validation of two datasets. The summary data for WBC counts were extracted from a recent large GWAS of the European ancestry individuals. We obtained GWAS data which related to HCC from UK Biobank (UKB). We performed univariable and multivariable MR analysis to identify whether genetic evidence of risk factors was significantly associated with HCC risks. Results In discovery dataset, multivariable MR analysis revealed that among the 8 traits of WBC counts, sum basophil neutrophil counts had an independent causal effect on occurrence of HCC. Sum basophil neutrophil counts: (OR = 0.437, P = 0.003, CI: 0.252–0.757). Similarly, in validation dataset, it was also observed that sum basophil neutrophil counts was the independent risk factor for HCC. Sum basophil neutrophil counts: (OR = 0.574, P = 0.021, CI: 0.358–0.920). Conclusion In European population, genetically-predicted the lower sum basophil neutrophil counts might be an independent risk factor of HCC.