Association between immune cells and multiple cancers: Insights from Mendelian randomization and gene-based analysis.

To investigate the roles of immune cells in cancer, we conducted Mendelian randomization (MR) analyses of 731 immune cells and 16 site-specific cancers, alongside gene-based and enrichment analyses. MR identified 79 significant associations (46 protective, 33 risk-enhancing). Key findings include BAFF-R on B cells lowering melanoma risk, and CD27 on B cells increasing lung cancer risk. Associations were also observed with breast, ovarian, cervical, and other cancers, but no significant association was found with oral cavity or pancreatic cancers. Gene-based analysis revealed 61 shared genes between immune cells and cancers. 56 genes were associated with prostate cancer, 30 with lung cancer, three with breast cancer, two with cervical cancer, and one with melanoma. Interestingly, several prostate cancer-associated genes were also associated with breast, cervical, and lung cancers. These findings suggest potential biological mechanisms linking immune cells to cancer development and progression, highlighting the complex role of the immune system in cancer.