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

TL;DR

This study explores whether uterine fibroids and breast cancer causally influence each other in East Asian women using genetic data.

Contribution

The study is the first to use bidirectional Mendelian randomization in East Asian populations to investigate the causal relationship between uterine fibroids and breast cancer.

Findings

Genetically predicted uterine fibroids showed a borderline positive association with breast cancer risk.

Breast cancer was found to have a significant causal effect on uterine fibroids.

No significant heterogeneity was observed in the genetic associations analyzed.

Abstract

Background/Objectives: 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. Methods: 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). Results: The SNPs with (p < 5.0 × 10−8) were selected as instrumental variables for UF (n = 16) and BC (n = 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; p = 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; p < 0.001 in IVW). Conclusions: 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.

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