ArticleEnvironmental geochemistry and health2025
The significance of organophosphate flame retardants in patients with esophageal squamous cell carcinoma.
Article in Environmental geochemistry and health, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Esophageal squamous cell carcinoma (ESCC) is a leading cause of cancer-related mortality in Taiwan, and has a poor prognosis despite treatment advances. Emerging evidence suggests environmental contaminants, including organophosphate flame retardants (OPFRs), as potential cancer contributors. This study aims to investigate the association between exposure to OPFRs and ESCC. A case-control study with 133 ESCC patients and 133 controls was conducted. Urinary concentrations of 10 OPFRs, including 5 triesters (TDCPP, TCEP, TBEP, TNBP, TPHP) and their corresponding diesters (BDCPP, BCEP, DBEP, DNBP, DPHP), were measured using UPLC-MS/MS, and the associations between OPFR levels and ESCC risk was analyzed. Survival analyses were also performed to assess prognostic impact. In vitro and in vivo experiments were conducted to explore cytotoxic effects and pathological changes induced by OPFRs, with pathways identified via RNA sequencing and gene set enrichment analysis (GSEA). Higher detection rates of BDCPP, BCEP, and TDCPP were observed in ESCC patients, with TDCPP showing the strongest association with ESCC (odds ratio [OR] = 2.58, p = 0.005) and the poorest survival outcome (hazard ratio [HR] = 1.91, p = 0.021). In cell culture experiments, TDCPP induced cytotoxicity, oxidative stress, and inhibited colony formation. In a murine animal model, combined TDCPP and 4-NQO exposure led to a significantly higher incidence of ESCC compared to 4-NQO alone. RNA sequencing and GSEA analysis identified several differentially expressed genes and pathways related to immune response and cellular stress. This study highlights TDCPP as a potential environmental risk factor for ESCC, emphasizing the importance of considering environmental exposures in patients with ESCC, and the need for further research into the carcinogenic impact of OPFRs.
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