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      Thyroid cancer and endocrine disruptive chemicals: a case–control study on per-fluoroalkyl substances and other persistent organic pollutants

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          Abstract

          Objective

          The aim was to evaluate the possible association between some endocrine disruptive chemicals and thyroid cancer (TC) in an Italian case–control cohort.

          Methods

          We enrolled 112 TC patients and 112 sex- and age-matched controls without known thyroid diseases. Per- and poly-fluoroalkyl substances (PFAS), poly-chlorinated biphenyls (PCBs), and dichlorodiphenyltrichloroethane (4,4′-DDT and 4,4′-DDE) were measured in the serum by liquid or gas chromatography–mass spectrometry. Unconditional logistic regression, Bayesan kernel machine regression and weighted quantile sum models were used to estimate the association between TC and pollutants’ levels, considered individually or as mixture. BRAF V600E mutation was assessed by standard methods.

          Results

          The detection of perfluorodecanoic acid (PFDA) was positively correlated to TC (OR = 2.03, 95% CI: 1.10–3.75, P = 0.02), while a negative association was found with perfluorohexanesulfonic acid (PFHxS) levels (OR = 0.63, 95% CI: 0.41–0.98, P = 0.04). Moreover, perfluorononanoic acid (PFNA) was positively associated with the presence of thyroiditis, while PFHxS and perfluorooctane sulfonic acid (PFOS) with higher levels of presurgical thyroid-stimulating hormone (TSH). PFHxS, PFOS, PFNA, and PFDA were correlated with less aggressive TC, while poly-chlorinated biphenyls (PCB-105 and PCB-118) with larger and more aggressive tumors. Statistical models showed a negative association between pollutants’ mixture and TC. BRAF V600E mutations were associated with PCB-153, PCB-138, and PCB-180.

          Conclusion

          Our study suggests, for the first time in a case–control population, that exposure to some PFAS and PCBs associates with TC and some clinical and molecular features. On the contrary, an inverse correlation was found with both PFHxS and pollutants’ mixture, likely due to a potential reverse causality.

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          Most cited references62

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          2015 American Thyroid Association Management Guidelines for Adult Patients with Thyroid Nodules and Differentiated Thyroid Cancer: The American Thyroid Association Guidelines Task Force on Thyroid Nodules and Differentiated Thyroid Cancer.

          Thyroid nodules are a common clinical problem, and differentiated thyroid cancer is becoming increasingly prevalent. Since the American Thyroid Association's (ATA's) guidelines for the management of these disorders were revised in 2009, significant scientific advances have occurred in the field. The aim of these guidelines is to inform clinicians, patients, researchers, and health policy makers on published evidence relating to the diagnosis and management of thyroid nodules and differentiated thyroid cancer.
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            The Eighth Edition AJCC Cancer Staging Manual: Continuing to build a bridge from a population-based to a more "personalized" approach to cancer staging.

            The American Joint Committee on Cancer (AJCC) staging manual has become the benchmark for classifying patients with cancer, defining prognosis, and determining the best treatment approaches. Many view the primary role of the tumor, lymph node, metastasis (TNM) system as that of a standardized classification system for evaluating cancer at a population level in terms of the extent of disease, both at initial presentation and after surgical treatment, and the overall impact of improvements in cancer treatment. The rapid evolution of knowledge in cancer biology and the discovery and validation of biologic factors that predict cancer outcome and response to treatment with better accuracy have led some cancer experts to question the utility of a TNM-based approach in clinical care at an individualized patient level. In the Eighth Edition of the AJCC Cancer Staging Manual, the goal of including relevant, nonanatomic (including molecular) factors has been foremost, although changes are made only when there is strong evidence for inclusion. The editorial board viewed this iteration as a proactive effort to continue to build the important bridge from a "population-based" to a more "personalized" approach to patient classification, one that forms the conceptual framework and foundation of cancer staging in the era of precision molecular oncology. The AJCC promulgates best staging practices through each new edition in an effort to provide cancer care providers with a powerful, knowledge-based resource for the battle against cancer. In this commentary, the authors highlight the overall organizational and structural changes as well as "what's new" in the Eighth Edition. It is hoped that this information will provide the reader with a better understanding of the rationale behind the aggregate proposed changes and the exciting developments in the upcoming edition. CA Cancer J Clin 2017;67:93-99. © 2017 American Cancer Society.
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              Polyfluoroalkyl Chemicals in the U.S. Population: Data from the National Health and Nutrition Examination Survey (NHANES) 2003–2004 and Comparisons with NHANES 1999–2000

              Background Polyfluoroalkyl chemicals (PFCs) have been used since the 1950s in numerous commercial applications. Exposure of the general U.S. population to PFCs is widespread. Since 2002, the manufacturing practices for PFCs in the United States have changed considerably. Objectives We aimed to assess exposure to perfluorooctane sulfonic acid (PFOS), perfluorooctanoic acid (PFOA), perfluorohexane sulfonic acid (PFHxS), perfluorononanoic acid (PFNA), and eight other PFCs in a representative 2003–2004 sample of the general U.S. population ≥ 12 years of age and to determine whether serum concentrations have changed since the 1999–2000 National Health and Nutrition Examination Survey (NHANES). Methods By using automated solid-phase extraction coupled to isotope dilution–high-performance liquid chromatography–tandem mass spectrometry, we analyzed 2,094 serum samples collected from NHANES 2003–2004 participants. Results We detected PFOS, PFOA, PFHxS, and PFNA in > 98% of the samples. Concentrations differed by race/ethnicity and sex. Geometric mean concentrations were significantly lower (approximately 32% for PFOS, 25% for PFOA, 10% for PFHxS) and higher (100%, PFNA) than the concentrations reported in NHANES 1999–2000 (p < 0.001). Conclusions In the general U.S. population in 2003–2004, PFOS, PFOA, PFHxS, and PFNA serum concentrations were measurable in each demographic population group studied. Geometric mean concentrations of PFOS, PFOA, and PFHxS in 2003–2004 were lower than in 1999–2000. The apparent reductions in concentrations of PFOS, PFOA, and PFHxS most likely are related to discontinuation in 2002 of industrial production by electrochemical fluorination of PFOS and related perfluorooctanesulfonyl fluoride compounds.

                Author and article information

                Journal
                Eur Thyroid J
                Eur Thyroid J
                ETJ
                European Thyroid Journal
                Bioscientifica Ltd (Bristol )
                2235-0640
                2235-0802
                20 May 2024
                24 April 2024
                01 June 2024
                : 13
                : 3
                : e230192
                Affiliations
                [1 ]Department of Endocrine and Metabolic Diseases , Istituto Auxologico Italiano IRCCS, Milan, Italy
                [2 ]Department of Pathophysiology and Transplantation , University of Milan, Milan, Italy
                [3 ]Department of Biotechnology and Translational Medicine , University of Milan, Milan, Italy
                [4 ]Department of Clinical , Forensic and Environmental Toxicology, University hospital of Liege (CHU Liège), CHU (B35), Liege, Belgium
                [5 ]Center for Interdisciplinary Research on Medicines (C.I.R.M.) , University of Liege (ULiège), CHU (B35), Liege, Belgium
                [6 ]PhD Program in Experimental Medicine , University of Milan, Milan, Italy
                Author notes
                Correspondence should be addressed to L Fugazzola: laura.fugazzola@ 123456unimi.it; l.fugazzola@ 123456auxologico.it

                *(V Cirello and M Lugaresi contributed equally to this work)

                Author information
                http://orcid.org/0000-0002-8795-5226
                http://orcid.org/0000-0001-5372-0982
                Article
                ETJ-23-0192
                10.1530/ETJ-23-0192
                11227063
                38657654
                41dc1a15-cf73-4f2a-a9c6-5992cdaaf3be
                © the author(s)

                This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.

                History
                : 18 September 2023
                : 24 April 2024
                Funding
                Funded by: Ministry of Health, doi http://dx.doi.org/10.13039/100009647;
                Categories
                Research
                ETJ-environment-thyroid-function, Environment and thyroid function
                Custom metadata
                ETJ-environment-thyroid-function

                braf,endocrine disruptive chemicals,pcb,pfas,thyroid cancer
                braf, endocrine disruptive chemicals, pcb, pfas, thyroid cancer

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