Bidirectional Mendelian Randomization Analysis of the Causal Relationship Between Uterine Fibroids and Breast Cancer in East Asian Women

<b>Background/Objectives</b>: This study was designed to investigate the potential causal relationship between uterine fibroids (UF) and breast cancer (BC) using genetic data in East Asian populations. <b>Methods</b>: We conducted a bidirectional two-sample Mendelian randomization (MR) analysis of UF and BC, selecting exposure-associated single-nucleotide polymorphisms (SNPs) from Biobank Japan and extracting outcome associations from the China Kadoorie Biobank for both directions. The primary estimator was inverse-variance-weighted (IVW), with robustness assessed using the weighted median, MR-Egger regression, and the MR-pleiotropy residual sum and outlier (MR-PRESSO). <b>Results</b>: The SNPs with (<i>p</i> < 5.0 × 10^-8) were selected as instrumental variables for UF (<i>n</i> = 16) and BC (<i>n</i> = 7). There was no evidence of heterogeneity in either direction. Genetically predicted UF was positively associated with BC risk (odds ratio, 1.33; 95% confidence interval, 0.99-1.79; <i>p</i> = 0.063), although the association did not reach statistical significance in IVW. In addition, the causal effect of BC on UF was significant (odds ratio, 1.19; 95% confidence interval, 1.08-1.32; <i>p</i> < 0.001 in IVW). <b>Conclusions</b>: Our study suggested a borderline significant causal effect of UF on BC. Moreover, BC demonstrated a significant causal association with UF, underscoring the need for further research into the role of various mechanisms including estrogen in the relationship between the two diseases.