Supplementary Material for: Association between blood pressure and digestive tract cancers in European and Asian populations: A two-sample Mendelian randomization study

Objective: To examine the causal relationship between blood pressure and digestive tract cancers in European and Asian populations using Mendelian randomization (MR). Methods: Summary statistics for blood pressure traits and digestive tract cancers were obtained from large-scale genome-wide association studies in European (UK Biobank, FinnGen) and Asian (Biobank Japan, KoGES) cohorts. The inverse variance weighted (IVW) method was the primary analysis, with sensitivity tests including MR-Egger, weighted median, and MR-PRESSO to assess pleiotropy and robustness. Results: In European populations, no significant causal associations were observed between blood pressure traits and digestive tract cancers (all P > 0.05). In contrast, genetically predicted higher systolic blood pressure (SBP) was linked to increased colorectal cancer (CRC) risk in Asians (OR = 1.436, 95% CI: 1.102–1.869). Sensitivity analyses supported the robustness of this association. Conclusions: Elevated SBP appears to be a potential causal risk factor for CRC in Asian populations, whereas no such association was observed in Europeans. Nevertheless, the causal links between blood pressure and other digestive tract cancers, as well as the underlying biological mechanisms, remain to be verified. To advance this understanding, further studies are needed to confirm ancestry-specific mechanisms and to clarify the biological pathways underlying these findings. Keywords: blood pressure; colorectal cancer; digestive tract cancers; Mendelian randomization; ancestry