{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T12:16:35Z","timestamp":1790424995232,"version":"4.1.0"},"reference-count":55,"publisher":"Bioscientifica","issue":"1","license":[{"start":{"date-parts":[[2026,6,15]],"date-time":"2026-06-15T00:00:00Z","timestamp":1781481600000},"content-version":"vor","delay-in-days":159,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["journals.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2026,2,1]]},"abstract":"<jats:p>Monoethyl phthalate, a major metabolite of phthalate esters, is commonly found in the environment and has been linked to an increased risk of thyroid cancer. This study uses network toxicology to predict molecular initiators involved in monoethyl phthalate-induced thyroid cancer and to explore causal relationships and biological mechanisms. We identified 72 common candidate genes of monoethyl phthalate and thyroid cancer from PubChem, CTD, STITCH, GeneCards, and OMIM databases and selected 48 genes for Mendelian randomization (MR) analysis. Using the IEU database and employing expression quantitative trait loci (eQTLs) as instrumental variables, we executed MR analysis to identify 10 monoethyl phthalate-related targets with potential causal relationship to thyroid cancer. Gene ontology and the Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses highlighted that the biological processes primarily involve intracellular receptor signaling, response to estradiol, nuclear receptor activity, ligand-activated transcription factor activity, and cancer-related signaling pathways, such as the cell cycle and tryptophan metabolism. A protein\u2013protein interaction (PPI) network identified interactions between seven of these genes, revealing five core genes (ESR1, SKP2, CASP8, ARNT, and CDKN1B) as key candidate mediators in monoethyl phthalate-induced thyroid cancer. Molecular docking simulations suggested potential direct interactions between monoethyl phthalate and its protein products. Our findings propose 10 genes as potential mediators of monoethyl phthalate-induced thyroid cancer, with ESR1, SKP2, CASP8, ARNT, and CDKN1B highlighted as core factors potentially involved in thyroid cancer pathogenesis.<\/jats:p>","DOI":"10.1530\/etj-25-0198","type":"journal-article","created":{"date-parts":[[2026,1,7]],"date-time":"2026-01-07T16:43:43Z","timestamp":1767804223000},"update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-17","source":"Crossref","is-referenced-by-count":1,"title":["Network toxicology and Mendelian randomization reveal pathogenic factors of monoethyl phthalate-induced thyroid 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