The Causal Role of Uterine Fibroid in Keloid and Hypertrophic Scar: A Bidirectional Mendelian Randomization Study on European Populations

Background: The relationship between uterine fibroids and keloid/hypertrophic scars has been contradictory. Our research employs a bidirectional Mendelian Randomization (MR) approach to establish a clearer understanding of this potential causal link. Objective: This study aimed to determine the effect of uterine fibroids on keloid/hypertrophic scars and the effect of keloid/hypertrophic scars on uterine fibroids. Purpose: We aimed to demonstrate the relationship between uterine fibroids and keloid/ hypertrophic scars. Method: Our bidirectional MR study utilized summarized data from genome-wide association studies (GWAS) focused on European populations. Our primary tool for establishing causality was the Inverse-Variance Weighted (IVW) method. To reinforce the IVW findings, we also applied four alternative MR methods: MR-Egger, Maximum Likelihood, Weighted Mode, and Weighted Median. Result: The IVW method indicated a significant causal link, with uterine fibroids greatly raising the likelihood of developing keloids (Odds Ratio [OR] = 1.202, 95% Confidence Interval [CI]: 1.045-1.381; P=0.010) and hypertrophic scars (OR = 1.256, 95% CI: 1.039-1.519; P=0.018). Parallel results were observed with the MR-Egger, Maximum Likelihood, Weighted Mode, and Weighted Median methods. Sensitivity analyses indicated robustness in these findings, with no evidence of heterogeneity or horizontal pleiotropy. Conversely, the reverse MR analysis did not demonstrate an increased risk of uterine fibroids due to keloids or hypertrophic scars. Conclusion: This study elucidates a significant causal effect of uterine fibroids on the development of keloid and hypertrophic scars, offering valuable insights into their pathogenesis and potential therapeutic targets.