The impact of immune cells on the risk of breast cancer: a Mendelian randomization study.

BACKGROUND: The immune system is closely linked to the prognosis of breast cancer (BC). However, it remains unclear whether changes in immune cells contribute to the etiology of BC. METHODS: Genetic variants associated with immune cells and BC and its subtypes were extracted from summary data of genome-wide association studies (GWAS) to explore the risk effects of immune cells on BC. Multivariable mendelian randomization (MVMR) was used to assess the independent risk effects of significantly associated immune traits. RESULTS: After correction in MVMR, granulocyte count (OR = 0.900, 95%CI:0.840-0.963) significantly decreased the risk of ER + BC; CD38 B cells (OR = 1.276, 95%CI:1.086-1.500) significantly increased the risk of ER- BC; granulocyte count (OR = 0.905, 95%CI:0.828-0.989) significantly decreased the risk of ER- BC; CD19 B cells (OR = 0.945, 95%CI:0.913-0.978) significantly decreased the risk of triple-negative breast cancer; CD11c dendritic cells (OR = 1.109, 95%CI:1.024-1.200) significantly decreased the risk of her 2 + BC. Additionally, there were observed interactions between CD19 and CD25 B cells, as well as granulocytes and CD4/naive CD4 T cells. CONCLUSION: The current MR study underscores the significant role of immune cells in the pathogenesis of BC, revealing complex interactions among immune subtypes.