Genetic Susceptibility of Thrombin Measurement Levels and the Risk of Colon Adenocarcinoma: A Mendelian Randomization Study

<b>Aims/Background:</b> This investigation sought to establish a possible correlation between thrombin measurement levels and the risk of developing colon adenocarcinoma (COAD). <b>Methods:</b> Thrombin measurement levels were sourced from a study by Pietzner M (2020, PMID: 33328453) and integrated into the IEU database. Data on COAD were obtained from the FinnGen database (2021, C3_COLON_ADENO). Various analytical methods were used to assess the relationship, including inverse variance weighting (IVW), mendelian randomization-Egger (MR-Egger) regression, as well as weighted median and mode techniques. Sensitivity analyses were performed, including Cochran's Q test, MR-Egger intercept test, mendelian randomization Pleiotropy RESidual Sum and Outlier (MR-PRESSO), along with leave-one-out analysis, to ensure the robustness of the results. <b>Results:</b> The IVW analysis indicated a significant inverse association between elevated thrombin levels and the risk of COAD (odds ratio (OR) = 0.76, 95% CI = 0.66-0.88, <i>p</i> = 0.0003). These findings were supported by the weighted median analysis (OR = 0.78, 95% CI = 0.68-0.90, <i>p</i> = 0.0006) and the weighted mode analysis (OR = 0.78, 95% CI = 0.68-0.88, <i>p</i> = 0.0017). <b>Conclusion:</b> This research identified an inverse causal relationship between thrombin measurement levels and the incidence of COAD, suggesting that higher thrombin levels are associated with a reduced risk of developing COAD.