Abstract
BACKGROUND: Breast cancer remains a significant global health challenge. Understanding its etiological factors, particularly the role of immune system components, is crucial. This study leverages Mendelian randomization (MR) to investigate the causal relationship between various immune cell features and the risk of developing breast cancer. METHODS: Utilizing two-sample MR analysis, we examined 731 immune cell features across 7 groups for their potential causal links to breast cancer. We analyzed genome-wide association studies (GWAS) data of 257,730 Europeans, comprising 17,389 cases and 240,341 controls, focusing on 24,133,589 single nucleotide polymorphisms (SNPs). Instrumental variables (IVs) were selected based on genetic associations, with rigorous statistical methods employed, including inverse variance weighting (IVW) and weighted median-based estimation. RESULTS: Our analysis identified 20 immunophenotypes with significant causal associations with breast cancer risk. Notably, contain B cell, mature T cell, T + B + NK (TBNK) cells, regulatory T (Treg) cell, Classic dendritic cells (cDCs), Monocyte, and Myeloid cell group features displayed positive or negative correlations with breast cancer. For instance, specific B cell phenotypes were found to have both positive and negative causal relationships with breast cancer. Additionally, reverse MR analysis revealed no significant causal effects of breast cancer on these immune characteristics. CONCLUSIONS: This study underscores the complex interplay between various immune cell phenotypes and breast cancer risk. The identified immunophenotypes could be potential biomarkers or targets for future therapeutic interventions. Our findings contribute to a deeper understanding of the immunological dimensions of breast cancer etiology.