Xin Pei, Wang Lei, Chen Xianyang, Li Huazhi, Jiang Nan
Department of General Surgery, Chuiyangliu Hospital, Tsinghua University, Beijing, 100022, China.
Zhongguancun Biomedical Big Data Center, Zhongguancun Big Data Industry Alliance, Beijing, China.
Discov Oncol. 2025 Jul 19;16(1):1377. doi: 10.1007/s12672-025-03206-7.
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.
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 . Inverse variance weighted (IVW) is adopted as the main method.
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).
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.
自身免疫性甲状腺炎（AIT）与乳腺癌之间的关联仍不明确，且相关介导因素尚未厘清。在本研究中，我们旨在探寻AIT与乳腺癌之间可能存在的因果关系及介导因素。
我们采用双向孟德尔随机化（MR）分析来探究因果关联及潜在的介导效应。我们利用全基因组关联研究（GWAS）数据构建工具变量。我们提取了与暴露因素显著相关的单核苷酸多态性（SNP），显著性阈值设定为p < 1.0×10 。采用逆方差加权（IVW）作为主要方法。
当暴露于AIT时，所有方法均表明AIT会增加患乳腺癌的风险（OR值均>1且P < 0.05）。当暴露于乳腺癌时，未发现显著结果。对1400种代谢物和211种肠道微生物群进行单因素MR分析，结果显示AIT与7 - 甲基黄嘌呤存在显著因果关系（IVW：95%可信区间0.001 - 0.059；p = 0.039）。反之则不存在因果关系。7 - 甲基黄嘌呤与乳腺癌存在因果关系（95%可信区间1.032 - 1.203；p = 0.006）。在AIT对乳腺癌的分析中加入7 - 甲基黄嘌呤进行多因素MR分析，结果仍然显著，AIT的IVW（95%可信区间0.007 - 0.055；p = 0.011），7 - 甲基黄嘌呤的IVW（95%可信区间0.031 - 0.200；P = 0.007）。
AIT可增加患乳腺癌的风险，反之不存在因果联系。在1400种代谢物中，7 - 甲基黄嘌呤是AIT导致乳腺癌的一个介导因素。在211种肠道微生物分类群中，不存在从AIT到乳腺癌的介导因素。
