Mediating factors between autoimmune thyroiditis and breast cancer: a bidirectional Mendelian randomization study

Area of Science:

• Endocrinology and Oncology
• Metabolomics
• Genetics

Background:

• The relationship between autoimmune thyroiditis (AIT) and breast cancer remains unclear, with limited understanding of potential mediating factors.
• Investigating causal links and mediators is crucial for understanding disease pathways and developing targeted interventions.

Purpose of the Study:

• To investigate the potential causal association between autoimmune thyroiditis (AIT) and breast cancer.
• To identify potential mediating factors, including metabolites and gut microbiome, in the AIT-breast cancer relationship.

Main Methods:

• Utilized a bidirectional Mendelian Randomization (MR) analysis employing Genome-Wide Association Studies (GWAS) data.
• Instrumental variables were constructed using single nucleotide polymorphisms (SNPs) with a significance threshold of p < 1.0 × 10^-5.
• Inverse variance weighted (IVW) method was the primary analytical approach, with single-factor and multi-factor MR analyses performed for metabolites and gut microbiome data.

Main Results:

• Autoimmune thyroiditis (AIT) was found to significantly increase the risk of breast cancer (OR > 1, P < 0.05).
• No significant causal association was observed in the reverse direction (breast cancer to AIT).
• 7-methylxanthine was identified as a significant mediator, showing a causal relationship with both AIT and breast cancer, while no gut microbiome mediators were found.

Conclusions:

• Autoimmune thyroiditis (AIT) is causally associated with an increased risk of breast cancer.
• 7-methylxanthine acts as a significant mediator in the pathway from AIT to breast cancer.
• The gut microbiome does not appear to mediate the relationship between AIT and breast cancer based on this analysis.