Mediating factors between autoimmune thyroiditis and breast cancer: a bidirectional Mendelian randomization study
Abstract Objective The association between autoimmune thyroiditis (AIT) and breast cancer was still confused and the mediators was not cleared. In this study, we designed to search a probably causality and mediators between AIT and breast cancer. Method We adopted a bidirectional Mendelian Randomiza...
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| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Springer
2025-07-01
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| Series: | Discover Oncology |
| Subjects: | |
| Online Access: | https://doi.org/10.1007/s12672-025-03206-7 |
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| Summary: | Abstract Objective The association between autoimmune thyroiditis (AIT) and breast cancer was still confused and the mediators was not cleared. In this study, we designed to search a probably causality and mediators between AIT and breast cancer. Method We adopted a bidirectional Mendelian Randomization (MR) analysis to explore the causal association and the potential mediating effects. We used Genome-Wide Association Studies (GWAS) data to construct instrumental variables. We extracted single nucleotide polymorphisms (SNPs) which were significantly associated with exposure factors and the significance threshold was set at p < 1.0 × 10 −5. Inverse variance weighted (IVW) is adopted as the main method. Results When AIT was exposed, all the methods indicated that AIT increased the risk of breast cancer (OR values were all > 1 and P < 0.05). When breast cancer was exposed, no significant result was found. Single-factor MR analysis was used for 1400 metabolites and 211 gut microbiome, and showed AIT has a significant causal relationship with 7-methylxanthine IVW: (95% CI 0.001–0.059; p = 0.039). In reverse, there was no causality. 7-Methylxanthine has a causal relationship with breast cancer (95% CI 1.032–1.203; p = 0.006). Multi-factor MR analysis was adopted by adding of 7-methylxanthine to AIT on Breast cancer, the result was still significant, the AIT IVW (95% CI 0.007–0.055; p = 0.011), 7-methylxanthine IVW (95% CI 0.031–0.200; P = 0.007). Conclusion AIT can increase the risk of breast cancer, there is no causal link in the reverse direction. Among the 1400 metabolites, 7-methylxanthine is a mediator of AIT to breast cancer. There were no mediators from AIT to breast cancer in the 211 gut microbiome taxa. |
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| ISSN: | 2730-6011 |