Genomic evidence based on eQTL data implicates endocrine disruptors as environmental risk factors for estrogen receptor-positive breast cancer

作者：Yanggang Hong, Jiajun Li, Zepeng Du, Nuo Xu, Qianru Yang, Jing-Xuan Zhou, Wanyi Shu · 发表于：International Journal of Surgery · 年份：2025 · DOI：10.1097/js9.0000000000002642 · 被引用次数：13 · 研究领域：Effects and risks of endocrine disrupting chemicals、Estrogen and related hormone effects、Epigenetics and DNA Methylation

BACKGROUND: Estrogen receptor-positive (ER+) breast cancer is the most common molecular subtype of breast cancer and is strongly influenced by hormonal and environmental factors. Endocrine-disrupting chemicals (EDCs), which interfere with hormone signaling, have been suggested to contribute to ER+ breast cancer risk, but causal mechanisms remain unclear. METHODS: We integrated chemical-gene interaction data from the TEDX and CTD databases with large-scale genomic datasets to investigate the relationship between EDC-regulated gene expression and ER+ breast cancer. A total of 5797 EDC-related genes were identified and filtered using cis-expression quantitative trait loci (cis-eQTL) data from eQTLGen. Mendelian randomization (MR) and colocalization analyses were performed using ER+ breast cancer GWAS summary statistics to assess causal associations and shared genetic signals. Interacting EDCs were mapped to colocalized genes. RESULTS: Among 4207 genes with available cis-eQTLs, 50 showed statistically significant associations (FDR < 0.05) with ER+ breast cancer. Of these, 24 genes, including CIRBP, JMJD1C, and TET2, demonstrated strong evidence of colocalization. Key EDCs, such as bisphenol A and phthalates, were identified to interact with multiple high-risk genes, suggesting potential environmental drivers of ER+ breast cancer. CONCLUSION: This study provides genetic evidence supporting the causal role of EDC-regulated gene expression in ER+ breast cancer. The integration of MR...