Deciphering the causality between micronutrients and esophageal cancer via Mendelian randomization.

Background: There is an ongoing debate about how micronutrients influence the risk of developing esophageal cancer (EC), requiring more definitive proof to ascertain their causal relationship.

Objective: The current study seeks to identify the causal relationship between 14 micronutrients and EC through Mendelian randomization (MR) methods.

Methods: We performed a two-sample MR analysis of micronutrients in relation to EC, using five different MR methodologies, chief among them the Inverse Variance Weighted method. To ascertain the direction of causal links, Steiger filtering was applied. The study culminated in a sensitivity analysis to test the robustness of the results.

Results: In the European population, iron (OR = 0.231, 95% CI: 0.073-0.727, P = 0.012) and magnesium (OR = 0.357, 95% CI: 0.143-0.894, P = 0.028) were associated with a reduced risk of EC, both showing suggestive evidence of a causal relationship. In Asian populations, however, no significant causal effects were found between the 14 micronutrients and EC. The direction of causality was validated across all results.

Conclusion: Among European populations, iron and magnesium intake is associated with a reduced risk of EC, a benefit not seen in Asian populations. Personalized strategies and region-specific advice are necessary for EC prevention and control.