Causal relationship between immune cells and prostate cancer: a Mendelian randomization study

Causal relationship between immune cells and prostate cancer: a Mendelian randomization study

19 March 2024 | Zhipeng Ye, Xinpei Deng, Jinhui Zhang, Ruonan Shao, Cailu Song, Jianfu Zhao and Hailin Tang
This study investigates the causal relationship between immune cells and prostate cancer using Mendelian randomization (MR). The research leverages genetic variants from genome-wide association studies (GWAS) to analyze the association between immune cell traits and prostate cancer risk. The primary analytical method used is inverse variance weighting (IVW), with comprehensive sensitivity analyses to assess heterogeneity and horizontal pleiotropy. The study identifies four immune cell traits that are causally associated with increased prostate cancer risk: CD127-CD8+ T cell %CD8+ T cell (OR = 1.0042, 95%CI:1.0011–1.0073, p = 0.0077), CD45RA on CD39+ resting CD4 regulatory T cell (OR = 1.0029, 95%CI:1.0008–1.0050, p = 0.0065), CD62L-Dendritic Cell Absolute Count (OR = 1.0016; 95%CI:1.0005–1.0026; p = 0.0039), and CX3CR1 on CD14+ CD16- monocyte (OR = 1.0024, 95%CI:1.0007–1.0040, p = 0.0060). Additionally, two immune cell traits are identified as causally protective: CD4 on monocyte (OR = 0.9975, 95%CI:0.9958–0.9992, p = 0.0047) and FSC-A on plasmacytoid Dendritic Cell (OR = 0.9983, 95%CI:0.9970–0.9995, p = 0.0070). Sensitivity analyses indicated no horizontal pleiotropy. The study provides evidence for a causal relationship between immune cells and prostate cancer, with implications for clinical diagnosis and treatment. The findings suggest that certain immune cell traits may promote or inhibit prostate cancer development. The MR analysis identified six immune cell types associated with prostate cancer risk, including T cells, monocytes, and dendritic cells. The study also highlights the complex interactions between immune cells and prostate cancer, offering new insights into the pathogenesis and treatment of prostate cancer. However, the study has limitations, including the potential for ethnic bias due to the European ancestry of the study population and the use of a low threshold for instrumental variable selection. Further research is needed to validate these findings and explore the underlying mechanisms.This study investigates the causal relationship between immune cells and prostate cancer using Mendelian randomization (MR). The research leverages genetic variants from genome-wide association studies (GWAS) to analyze the association between immune cell traits and prostate cancer risk. The primary analytical method used is inverse variance weighting (IVW), with comprehensive sensitivity analyses to assess heterogeneity and horizontal pleiotropy. The study identifies four immune cell traits that are causally associated with increased prostate cancer risk: CD127-CD8+ T cell %CD8+ T cell (OR = 1.0042, 95%CI:1.0011–1.0073, p = 0.0077), CD45RA on CD39+ resting CD4 regulatory T cell (OR = 1.0029, 95%CI:1.0008–1.0050, p = 0.0065), CD62L-Dendritic Cell Absolute Count (OR = 1.0016; 95%CI:1.0005–1.0026; p = 0.0039), and CX3CR1 on CD14+ CD16- monocyte (OR = 1.0024, 95%CI:1.0007–1.0040, p = 0.0060). Additionally, two immune cell traits are identified as causally protective: CD4 on monocyte (OR = 0.9975, 95%CI:0.9958–0.9992, p = 0.0047) and FSC-A on plasmacytoid Dendritic Cell (OR = 0.9983, 95%CI:0.9970–0.9995, p = 0.0070). Sensitivity analyses indicated no horizontal pleiotropy. The study provides evidence for a causal relationship between immune cells and prostate cancer, with implications for clinical diagnosis and treatment. The findings suggest that certain immune cell traits may promote or inhibit prostate cancer development. The MR analysis identified six immune cell types associated with prostate cancer risk, including T cells, monocytes, and dendritic cells. The study also highlights the complex interactions between immune cells and prostate cancer, offering new insights into the pathogenesis and treatment of prostate cancer. However, the study has limitations, including the potential for ethnic bias due to the European ancestry of the study population and the use of a low threshold for instrumental variable selection. Further research is needed to validate these findings and explore the underlying mechanisms.
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