Investigating the Causal Relationship between Immune Cell Phenotypes and Pancreatic Cancer Risk: A Mendelian Randomization Study

Abstract

Background: Pancreatic cancer (PC) is a highly lethal malignancy with poor clinical prognosis, whose development is associated with genetic and environmental factors. The immunophenotype, referring to the immune-related molecular markers on the surface of tumor cells, significantly impacts the progression, development, and treatment response of PC.

Objective: This study employed a two-sample Mendelian randomization (MR) bidirectional analysis to explore the association between immunophenotype and the risk of PC.

Methods: We collected datasets on 731 immune cells associated with PC from the Finngen database and GWAScatalog database. Reverse-variance weighted (RVW), weighted median (WM), and MR-Egger methods were applied to analyze the causal relationship between immune cells and PC. Cochran's Q test, MR-Egger regression, MR-PRESSO, and Leave-one-out methods were used to evaluate the stability and reliability of the study results.

Results: After bidirectional FDR correction, we found no statistically significant impact of PC on the immunophenotype. However, when investigating the causal effect of immunophenotype on PC, we found that among four immunophenotype categories (MFI, RC, AC, MP), 26 immune phenotypes were causally associated with PC (P < 0.05). Among these, seven immune phenotypes could significantly inhibit the occurrence and development of PC (IVW ≥ 0.05, OR ≥ 1), while another 19 immune phenotypes might lead to the incidence of PC (IVW < 0.05, OR < 1).

Conclusion: This study preliminarily reveals the causal relationship between immune cells and pancreatic cancer from a genetic perspective, providing an important theoretical basis for precision medicine and individualized treatment in the future.