Casual association between circulating white blood cell traits and colorectal cancer: A Mendelian Randomization Study

Background: The relationship between circulating white blood cell (WBC) traits and colorectal cancer (CRC) risk remains unclear.This study employs Mendelian randomization (MR) to investigate whether genetic variants associated with WBC traits are causally linked to the development of CRC.Methods: We utilized summary statistics from large-scale genome-wide association studies (GWAS) to identify single nucleotide polymorphisms (SNPs) associated with WBC traits, including total WBC count, neutrophils, lymphocytes, monocytes, and eosinophils.We then employed two-sample MR to assess the causal relationships between these WBC traits and CRC risk using publicly available GWAS data for CRC.Results: Our analysis identified several SNPs significantly associated with WBC traits and CRC risk.The findings suggest a significant inverse causal relationship between colorectal cancer (CRC) and white blood cell count (Odds Ratio = 0.888, 95% Confidence Interval = 0.800 -0.980, p = 0.026), as well as eosinophil count (Odds Ratio = 0.831, 95% Confidence Interval = 0.710 -0.973, p = 0.022).However, no significant associations were seen between monocyte cell count, lymphocyte cell count, or neutrophil cell count and CRC.Conclusion: This MR study suggests that higher circulating total white blood cell count and eosinophil count may be causally linked to decrease risk of colorectal cancer, highlighting the importance of immune regulation in cancer pathogenesis.Further investigations are warranted to elucidate the underlying mechanisms and assess the potential for WBC traits as biomarkers for CRC risk.