ABSTRACT
Introduction: Mycosis fungoides (MF), the most prevalent form of cutaneous T-cell lymphoma (CTCL), has been associated with a variety of environmental and occupational exposures. Flame-retardant clothing (FRC), in contrast to flame-resistant clothing, is chemically treated and may constitute a previously unrecognized occupational hazard. Objectives: To report an association between FRC and MF. Methods: After encountering several young male patients whose onset of MF coincided with the occupational use of FRC and occupation as fire fighters, we did a retrospective search. Additional biopsy proven MF patients with use of FRC were identified by the EPIC electronic medical record using the search terms "CTCL, mycosis fungoides, flame, and flame-retardant." Results: Eight MF patients, all males, ranging in age from 31 years to 64 years (median age, 35 years) with exposure to FRC were identified. MF remission was noted in three patients who discontinued FRC use and in one patient who used a cotton undershirt barrier, while disease persistence was noted in one patient who continued to use FRC. Conclusions: FRC appears to be associated with development of MF through chronic antigen stimulation. Use of FRC is an occupational hazard for fire fighters. Any patient whose MF coincides with use of FRC should avoid further exposure through avoidance or switching to clothing made from inherently flame-resistant fibers.
ABSTRACT
BACKGROUND: Zebrafish is a popular animal model used for high-throughput screening of chemical hazards, however, investigations of transcriptomic mechanisms of toxicity are still needed. Here, our goal was to identify genes and biological pathways that Aryl Hydrocarbon Receptor 2 (AHR2) Activators and flame retardant chemicals (FRCs) alter in developing zebrafish. Taking advantage of a compendium of phenotypically-anchored RNA sequencing data collected from 48-h post fertilization (hpf) zebrafish, we inferred a co-expression network that grouped genes based on their transcriptional response. RESULTS: Genes responding to the FRCs and AHR2 Activators localized to distinct regions of the network, with FRCs inducing a broader response related to neurobehavior. AHR2 Activators centered in one region related to chemical stress responses. We also discovered several highly co-expressed genes in this module, including cyp1a, and we subsequently show that these genes are definitively within the AHR2 signaling pathway. Systematic removal of the two chemical types from the data, and analysis of network changes identified neurogenesis associated with FRCs, and regulation of vascular development associated with both chemical classes. We also identified highly connected genes responding specifically to each class that are potential biomarkers of exposure. CONCLUSIONS: Overall, we created the first zebrafish chemical-specific gene co-expression network illuminating how chemicals alter the transcriptome relative to each other. In addition to our conclusions regarding FRCs and AHR2 Activators, our network can be leveraged by other studies investigating chemical mechanisms of toxicity.
Subject(s)
Zebrafish Proteins , Zebrafish , Animals , Base Sequence , Embryo, Nonmammalian/metabolism , Receptors, Aryl Hydrocarbon/genetics , Receptors, Aryl Hydrocarbon/metabolism , Transcriptome , Zebrafish/genetics , Zebrafish/metabolism , Zebrafish Proteins/geneticsABSTRACT
BACKGROUND: Thyroid cancer is the fastest increasing cancer in the U.S., and papillary thyroid cancer (PTC) accounts for >80% of incident cases. Increasing exposure to flame retardant chemicals (FRs) has raised concerns about their possible role in this 'epidemic'. The current study was designed to test the hypothesis that higher exposure to FRs is associated with increased odds of PTC. METHODS: PTC patients at the Duke Cancer Institute were approached and invited to participate. Age- and gender-matched controls were recruited from the Duke Health System and surrounding communities. Because suitable biomarkers of long-term exposure do not exist for many common FRs, and levels of FRs in dust are significantly correlated with exposure, relationships between FRs in household dust and PTC were evaluated in addition to available biomarkers. PTC status, measures of aggressiveness (e.g. tumor size) and BRAF V600E mutation were included as outcomes. RESULTS: Higher levels of some FRs, particularly decabromodiphenyl ether (BDE-209) and tris(2-chloroethyl) phosphate in dust, were associated with increased odds of PTC. Participants with dust BDE-209 concentrations above the median level were 2.29 times as likely to have PTC [95% confidence interval: 1.03, 5.08] compared to those with low BDE-209 concentrations. Associations varied based on tumor aggressiveness and mutation status; TCEP was more strongly associated with larger, more aggressive tumors and BDE-209 was associated with smaller, less aggressive tumors. CONCLUSIONS: Taken together, these results suggest exposure to FRs in the home, particularly BDE-209 and TCEP, may be associated with PTC occurrence and severity, and warrant further study.
Subject(s)
Carcinoma, Papillary/epidemiology , Environmental Pollutants/analysis , Flame Retardants/analysis , Halogenated Diphenyl Ethers/analysis , Organophosphates/analysis , Thyroid Neoplasms/epidemiology , Adult , Carcinoma, Papillary/genetics , Carcinoma, Papillary/pathology , Case-Control Studies , Dust/analysis , Environmental Monitoring , Female , Housing , Humans , Male , Middle Aged , Mutation , Proto-Oncogene Proteins B-raf/genetics , Thyroid Cancer, Papillary , Thyroid Neoplasms/genetics , Thyroid Neoplasms/pathologyABSTRACT
In the past decade, exposure to flame retardant chemicals has become a pressing health concern and widely discussed topic of public safety for firefighters in the United States. Working through local, state, and national unions and independent health and advocacy organizations, firefighters have made important contributions to efforts to restrict the use of certain flame retardants. Firefighters are key members in advocacy coalitions dedicated to developing new environmental health regulations and reforming flammability standards to reflect the best available fire science. Their involvement has been motivated by substantiated health concerns and critiques of deceptive lobbying practices by the chemical industry. Drawing on observations and interviews with firefighters, fire safety experts, and other involved stakeholders, this article describes why firefighters are increasingly concerned about their exposure to flame retardant chemicals in consumer products, and analyzes their involvement in state and national environmental health coalitions.