Multivariable Mendelian Randomization Analysis Reveals Potential Causal Effects between Immune Cells and Prostate Cancer Risk
Abstract
Background: Previous studies indicated that immune cells and Metabolites might play an important role in the occurrence and development of Prostate Cancer (PCa). Our study aimed to illustrate the causal effects between immune cells and metabolites and PCa risk, and the mediating role of metabolites between immune cells and PCa. Methods: This study utilized immune cells as Exposures, metabolites as Mediators, and PCa as Outcomes. Initially, immune cell and metabolite data were processed. Subsequently, a four-stage approach involved six Mendelian randomization analyses: Stage one focused on batch immune cell to PCa MR (MR 1); Stage two involved immune cell to PCa Reverse MR (MR 2); Stage three performed batch metabolite to PCa MR (MR 3); Stage four included three MR analyses: prostate carcinogenesis related immune cells to PCa-related metabolites MR yielding beta 1 (MR 4), PCa-related metabolites to PCa MR yielding beta 2 (MR 5), and prostate carcinogenesis related immune cells to PCa MR yielding beta All (MR 6). Finally, mediation and direct effects were computed. Results: Our research identified twenty-five immune cells and nine metabolites associated with the incidence of PCa. Among the most intriguing associations, genetically predicted “CD25 on IgD+ CD38– Unswitched Memory (unsw mem) cells” are linked to an increased risk of PCa, Notably, 14.6% (1.68%, 27.5%) of this risk is mediated through the metabolite “3-hydroxypyridine sulfate levels” with a mediated effect of 0.00235 (0.00027, 0.00442) and a p-value of 0.026751157. This indicates that an increase in “CD25 on IgD+ CD38– unsw mem cells” can promote the development of PCa by reducing the levels of “3-hydroxypyridine sulfate”. Conclusions: Our findings suggest that 3-hydroxypyridine sulfate mediates the association between CD25 on IgD+ CD38– unsw mem and increased PCa risk. This study unexpectedly found that elevated 3-hydroxypyridine sulfate levels may explain how coffee consumption could protect against PCa.
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