Immunocyte-mediated food intakes and colorectal cancer causal relationship insights from a large-scale Mendelian randomization study

In previous observational studies, a correlation between food intakes and colorectal cancer has been established. Immune cells play a crucial role in the occurrence and development of colorectal cancer, suggesting promising therapeutic avenues through immune cell interference. Food intakes, being the most easily modifiable variable in clinical practice, present a prospective therapeutic approach by modulating immune cells to suppress the occurrence and progression of colorectal cancer. However, elucidating the causal relationship between immune cell-mediated food intakes and colorectal cancer remains to be resolved. We employed a two-sample Mendelian randomization approach to investigate the causal relationship between food intakes and colorectal cancer. Furthermore, we utilized two-step Mendelian randomization and multivariable Mendelian randomization to delve into the mediating role of immune cell signaling in the causal relationship between food intakes and colorectal cancer. Leveraging publicly available genetic datasets, our analysis encompassed 903 traits, including 171 food intakes features, 731 immune cell features, and one trait associated with colorectal cancer. We identified causal relationships between three types of food intakes and colorectal cancer. Furthermore, our two-step Mendelian randomization analysis and multivariable Mendelian randomization analysis indicated that monocyte-mediated grapefruit intakes serve as a protective factor against colorectal cancer, B cell-mediated pulses intakes also act as a protective factor against colorectal cancer. To the best of our knowledge, we are the first to integrate immune cell features, food intakes features, and colorectal cancer data into Mendelian randomization analysis on a large scale. Our research findings suggest that adjusting food intakes to modulate immune cells holds promise as a preventive and protective measure against colorectal cancer, offering valuable prospects for clinical patient treatment.