Association between immune cells and breast cancer: A two-sample Mendelian randomization study

Area of Science:

• Immunology
• Genetics
• Oncology

Background:

• Breast cancer remains a leading cause of mortality worldwide.
• Understanding the interplay between the immune system and cancer development is crucial for novel therapeutic strategies.
• The role of specific circulating immune cell populations in breast cancer etiology requires further elucidation.

Purpose of the Study:

• To investigate the potential causal relationship between circulating immune cells and breast cancer incidence.
• To explore the protective or risk-modifying effects of immune cell profiles on breast cancer development.
• To identify specific immune cell-related genetic factors influencing breast cancer risk.

Main Methods:

• Employed a 2-sample Mendelian randomization (MR) approach.
• Utilized large-scale genome-wide association study (GWAS) data for exposure (circulating immune cells) and outcome (breast cancer).
• Applied inverse-variance weighting, Weighted Median, and MR-Egger regression analyses for robust estimation.

Main Results:

• A statistically significant protective association was found between the CD4RA gene (terminally differentiated CD4+ lymphocyte ratio) and breast cancer risk (OR: 0.9809, P=0.0089).
• This protective effect was consistently observed across multiple MR analysis methods.
• No significant heterogeneity or directional pleiotropy was detected, supporting the validity of the findings.

Conclusions:

• Circulating immune cells, particularly those influenced by the CD4RA gene, may exert a protective role in breast carcinogenesis.
• These findings offer potential for developing improved breast cancer risk prediction models and preventive strategies.
• Further functional studies are warranted to uncover the precise mechanisms underlying this immune-mediated protection.