Genetic Evidence for the Causal Link Between Coagulation Factors and the Risk of Ovarian Cancer: A Two-Sample Mendelian Randomization Study.

Abstract

Background: Prior investigations have suggested a significant association between coagulation factors and ovarian cancer; however, the precise nature of the causal relationship remains elusive. Our objective is to thoroughly investigate this causal link and delineate the influence of coagulation factors on the risk of ovarian cancer through a rigorous two-sample Mendelian randomization (MR) analysis.

Methods: Genetic instrumental variables representing coagulation factors were sourced from four distinct data repositories. Summary statistics pertaining to ovarian cancer were obtained from two extensive Genome-Wide Association Studies (GWAS) for primary and replication analyses, respectively. The primary Mendelian randomization (MR) analysis utilized the inverse-variance weighted (IVW) method. To fortify the reliability of our findings, additional analyses were conducted, including the weighted-median method, MR-Egger regression, MR pleiotropy residual sum and outlier test, Cochran's Q statistic test, MR-Egger intercept analysis, and leave-one-out method, among others.

Results: We identified four coagulation factors that were associated with the risk of ovarian cancer in the primary analysis, [odds ratio (OR): 1.365, 95% confidence interval (CI): 1.209-1.542, P <0.001 for von Willebrand factor measurement(vWF); OR: 1.060, 95% CI: 1.018-1.104, P = 0.005 for A disintegrin and metalloproteinase with thrombospondin motifs 13 (ADATMS13); OR: 1.317, 95% CI: 1.002-1.730, P = 0.048 for activated partial thromboplastin time (aPTT); OR: 1.139, 95% CI: 1.063-1.221, P <0.001 for coagulation Factor VIII (FVIII)]. In the meta-analysis, we found that higher levels of coagulation factor VII measurement(FVII) (OR=1.0007, 95% CI: 1.0001-1.0013, P=1.0007) was associated with increased ovarian cancer risk. The results of sensitivity analyses for these coagulation factors were consistent (P<0.05).

Conclusion: Our systematic analyses have furnished evidence suggesting a plausible causal association between FVII and the susceptibility to ovarian cancer. Further investigations are warranted to delineate the mechanistic pathways through which coagulation factors influence the progression of ovarian cancer.