Thyroid Cancer and Endocrine Disruptive Chemicals: A Case-Control Study on Per-fluoroalkyl Substances (PFAS) and Other Persistent Organic Pollutants (POPs).
[en] [en] OBJECTIVE: 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. BRAFV600E 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 pre-surgical 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 tumours. Statistical models showed a negative association between pollutants' mixture and TC. BRAFV600E mutations resulted associated with PCB-153, PCB-138 and PCB-180.
CONCLUSIONS: 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.
Disciplines :
Pharmacy, pharmacology & toxicology
Author, co-author :
Cirello, Valentina; V Cirello , Division of Endocrine and Metabolic Diseases and Laboratory of Endocrine and Metabolic Research, Istituto Auxologico Italiano Istituto di Ricovero e Cura a Carattere Scientifico, Milano, 20095, Italy
Lugaresi, Marina; M Lugaresi, Milan, Italy
Moneta, Claudia; C Moneta, Department of Pathophysiology and Transplantation, University of Milan, Milano, -, Italy
Dufour, Patrice ; Centre Hospitalier Universitaire de Liège - CHU > > Service de toxicologie clinique, médicolégale, environnementale et en entreprise ; P Dufour, Liege, Belgium
Manzo, Alessandro; A Manzo, Milan, Italy
Carbone, Erika; E Carbone, Milan, Italy
Colombo, Carla; C Colombo, University of Milan, Milano, 20149, Italy
Fugazzola, Laura; L Fugazzola, MILANO, 20149, Italy
Charlier, Corinne ; Université de Liège - ULiège > Département de pharmacie > Chimie toxicologique ; C Charlier, Liege, Belgium
Pirard, Catherine ; Université de Liège - ULiège > Département des sciences de la santé publique ; C Pirard, Liege, Belgium
Language :
English
Title :
Thyroid Cancer and Endocrine Disruptive Chemicals: A Case-Control Study on Per-fluoroalkyl Substances (PFAS) and Other Persistent Organic Pollutants (POPs).
Pizzato M, Li M, Vignat J, Laversanne M, Singh D, La Vecchia C & Vaccarella S. The epidemiological landscape of thyroid cancer worldwide: GLOBOCAN estimates for incidence and mortality rates in 2020. Lancet. Diabetes and Endocrinology 2022 10 264-272. (https://doi.org/10.1016/S2213-8587(22)00035-3)
James BC, Mitchell JM, Jeon HD, Vasilottos N, Grogan RH & Aschebrook-Kilfoy B. An update in international trends in incidence rates of thyroid cancer, 1973-2007. Cancer Causes and Control 2018 29 465-473. (https://doi.org/10.1007/s10552-018-1023-2)
Miranda-Filho A, Lortet-Tieulent J, Bray F, Cao B, Franceschi S, Vaccarella S & Dal Maso L. Thyroid cancer incidence trends by histology in 25 countries: a population-based study. Lancet. Diabetes and Endocrinology 2021 9 225-234. (https://doi. org/10.1016/S2213-8587(21)00027-9)
Vigneri R, Malandrino P & Vigneri P. The changing epidemiology of thyroid cancer: why is incidence increasing? Current Opinion in Oncology 2015 27 1-7. (https://doi.org/10.1097/ CCO.0000000000000148)
van Gerwen M, Alsen M & Genden E. It May Not All Be overdiagnosis: the Potential Role of Environmental Exposures in the thyroid Cancer Incidence Increase. Epidemiology 2022 33 607-610. (https://doi.org/10.1097/EDE.0000000000001519)
Pearce EN. Endocrine disruptors and thyroid health. Endocrine Practice 2024 30 172-176. (https://doi.org/10.1016/j. eprac.2023.11.002)
Fiore E & Vitti P. Serum TSH and risk of papillary thyroid cancer in nodular thyroid disease. Journal of Clinical Endocrinology and Metabolism 2012 97 1134-1145. (https://doi.org/10.1210/jc.2011-2735)
Calafat AM, Wong LY, Kuklenyik Z, Reidy JA & Needham LL. 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. Environmental Health Perspectives 2007 115 1596-1602. (https://doi.org/10.1289/ ehp.10598)
Fernández-Rodríguez M, Arrebola JP, Artacho-Cordón F, Amaya E, Aragones N, Llorca J, Perez-Gomez B, Ardanaz E, Kogevinas M, Castano-Vinyals G, et al. Levels and predictors of persistent organic pollutants in an adult population from four Spanish regions. Science of the Total Environment 2015 538 152-161. (https://doi. org/10.1016/j.scitotenv.2015.07.162)
Pirard C, Compere S, Firquet K & Charlier C. The current environmental levels of endocrine disruptors (mercury, cadmium, organochlorine pesticides and PCBs) in a Belgian adult population and their predictors of exposure. International Journal of Hygiene and Environmental Health 2018 221 211-222. (https://doi. org/10.1016/j.ijheh.2017.10.010)
Safe S. Recent advances in understanding endocrine disruptors: DDT and related compounds. Faculty Reviews 2020 9 7. (https://doi. org/10.12703/b/9-7)
Zhuo H, Huang H, Sjodin A, Jin L, Ma S, Denic-Roberts H, Warren JL, Jones R, Davis M, Sun P, et al. A nested case-control study of serum polychlorinated biphenyls and papillary thyroid cancer risk among U.S. military service members. Environmental Research 2022 212 113367. (https://doi.org/10.1016/j.envres.2022.113367)
Louis LM, Lerro CC, Friesen MC, Andreotti G, Koutros S, Sandler DP, Blair A, Robson MG & Beane Freeman LE. A prospective study of cancer risk among Agricultural Health Study farm spouses associated with personal use of organochlorine insecticides. Environmental Health 2017 16 95. (https://doi.org/10.1186/s12940- 017-0298-1)
Rosenfeld PE, Spaeth KR, Remy LL, Byers V, Muerth SA, Hallman RC, Summers-Evans J & Barker S. Perfluoroalkyl substances exposure in firefighters: sources and implications. Environmental Research 2023 220 115164. (https://doi.org/10.1016/j. envres.2022.115164)
Pavuk M, Cerhan JR, Lynch CF, Schecter A, Petrik J, Chovancova J & Kocan A. Environmental exposure to PCBs and cancer incidence in eastern Slovakia. Chemosphere 2004 54 1509-1520. (https://doi. org/10.1016/j.chemosphere.2003.10.038)
Barry V, Winquist A & Steenland K. Perfluorooctanoic acid (PFOA) exposures and incident cancers among adults living near a chemical plant. Environmental Health Perspectives 2013 121 1313-1318. (https://doi.org/10.1289/ehp.1306615)
Consonni D, Straif K, Symons JM, Tomenson JA, van Amelsvoort LGPM, Sleeuwenhoek A, Cherrie JW, Bonetti P, Colombo I, Farrar DG, et al. Cancer risk among tetrafluoroethylene synthesis and polymerization workers. American Journal of Epidemiology 2013 178 350-358. (https:// doi.org/10.1093/aje/kws588)
Ennour-Idrissi K, Ayotte P & Diorio C. Persistent organic pollutants and breast cancer: a systematic review and critical appraisal of the literature. Cancers 2019 11. (https://doi.org/10.3390/cancers11081063)
Liu M, Zhang G, Meng L, Han X, Li Y, Shi Y, Li A, Turyk ME, Zhang Q & Jiang G. Associations between novel and legacy per- and polyfluoroalkyl substances in human serum and thyroid cancer: a case and healthy population in Shandong Province, East China. Environmental Science and Technology 2022 56 6144-6151. (https:// doi.org/10.1021/acs.est.1c02850)
Li H, Yang M, Yang J, Seery S, Ma C, Liu Y, Zhang X, Li A & Guo H. Per- and polyfluoroalkyl substances and the associated thyroid cancer risk: a case-control study in China. Chemosphere 2023 337 139411. (https://doi.org/10.1016/j.chemosphere.2023.139411)
van Gerwen M, Colicino E, Guan H, Dolios G, Nadkarni GN, Vermeulen RCH, Wolff MS, Arora M, Genden EM & Petrick LM. Per-and polyfluoroalkyl substances (PFAS) exposure and thyroid cancer risk. EBiomedicine 2023 97 104831. (https://doi.org/10.1016/j. ebiom.2023.104831)
Madrigal JM, Troisi R, Surcel HM, Öhman H, Kivelä J, Kiviranta H, Rantakokko P, Koponen J, Medgyesi DN, Kitahara CM, et al. Prediagnostic serum concentrations of per- and polyfluoroalkyl substances and risk of papillary thyroid cancer in the Finnish Maternity Cohort. International Journal of Cancer 2024 154 979-991. (https://doi.org/10.1002/ijc.34776)
Vieira VM, Hoffman K, Shin HM, Weinberg JM, Webster TF & Fletcher T. Perfluorooctanoic acid exposure and cancer outcomes in a contaminated community: a geographic analysis. Environmental Health Perspectives 2013 121 318-323. (https://doi. org/10.1289/ehp.1205829)
Messmer MF, Salloway J, Shara N, Locwin B, Harvey MW & Traviss N. Risk of cancer in a community exposed to per- and poly-fluoroalkyl substances. Environmental Health Insights 2022 16 11786302221076707. (https://doi.org/10.1177/11786302221076707)
Alsen M, Leung AM & van Gerwen M. Per- and polyfluoroalkyl substances (PFAS) in Community Water Systems (CWS) and the risk of thyroid cancer: an ecological study. Toxics 2023 11. (https://doi. org/10.3390/toxics11090786)
Cathey AL, Nguyen VK, Colacino JA, Woodruff TJ, Reynolds P & Aung MT. Exploratory profiles of phenols, parabens, and per- and poly-fluoroalkyl substances among NHANES study participants in association with previous cancer diagnoses. Journal of Exposure Science and Environmental Epidemiology 2023 33 687-698. (https:// doi.org/10.1038/s41370-023-00601-6)
Grice MM, Alexander BH, Hoffbeck R & Kampa DM. Self-reported medical conditions in perfluorooctanesulfonyl fluoride manufacturing workers. Journal of Occupational and Environmental Medicine 2007 49 722-729. (https://doi.org/10.1097/ JOM.0b013e3180582043)
Liu J, Song L, Zhan J, Zhong Y & Shi Z. Occurrence of legacy and alternative per- and polyfluoroalkyl substances in serum from high exposure population and their disrupting effects on serum lipids and thyroid function. Science of the Total Environment 2023 878 162988. (https://doi.org/10.1016/j.scitotenv.2023.162988)
Lerro CC, Jones RR, Langseth H, Grimsrud TK, Engel LS, Sjödin A, Choo-Wosoba H, Albert P & Ward MH. A nested case-control study of polychlorinated biphenyls, organochlorine pesticides, and thyroid cancer in the Janus Serum Bank cohort. Environmental Research 2018 165 125-132. (https://doi.org/10.1016/j.envres.2018.04.012)
Petrosino V, Motta G, Tenore G, Coletta M, Guariglia A & Testa D. The role of heavy metals and polychlorinated biphenyls (PCBs) in the oncogenesis of head and neck tumors and thyroid diseases: a pilot study. Biometals 2018 31 285-295. (https://doi.org/10.1007/ s10534-018-0091-9)
Han X, Meng L, Li Y, Li A, Turyk ME, Yang R, Wang P, Xiao K, Li W, Zhao J, et al. Associations between exposure to persistent organic pollutants and thyroid function in a case-control study of East China. Environmental Science and Technology 2019 53 9866-9875. (https://doi.org/10.1021/acs.est.9b02810)
Mathur A, Moses W, Rahbari R, Khanafshar E, Duh QY, Clark O & Kebebew E. Higher rate of BRAF mutation in papillary thyroid cancer over time: a single-institution study. Cancer 2011 117 4390-4395. (https://doi.org/10.1002/cncr.26072)
Romei C, Fugazzola L, Puxeddu E, Frasca F, Viola D, Muzza M, Moretti S, Nicolosi ML, Giani C, Cirello V, et al. Modifications in the papillary thyroid cancer gene profile over the last 15 years. Journal of Clinical Endocrinology and Metabolism 2012 97 E1758-E1765. (https://doi.org/10.1210/jc.2012-1269)
Jung CK, Little MP, Lubin JH, Brenner AV, Wells SAJ, Sigurdson AJ & Nikiforov YE. The increase in thyroid cancer incidence during the last four decades is accompanied by a high frequency of BRAF mutations and a sharp increase in RAS mutations. Journal of Clinical Endocrinology and Metabolism 2014 99 E276-E285. (https:// doi.org/10.1210/jc.2013-2503)
Frasca F, Nucera C, Pellegriti G, Gangemi P, Attard M, Stella M, Loda M, Vella V, Giordano C, Trimarchi F, et al. BRAF(V600E) mutation and the biology of papillary thyroid cancer. Endocrine-Related Cancer 2008 15 191-205. (https://doi.org/10.1677/ERC-07-0212)
Haugen BR, Alexander EK, Bible KC, Doherty GM, Mandel SJ, Nikiforov YE, Pacini F, Randolph GW, Sawka AM, Schlumberger M, et al. 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 2016 26 1-133. (https://doi.org/10.1089/thy.2015.0020)
Amin MB, Greene FL, Edge SB, Compton CC, Gershenwald JE, Brookland RK, Meyer L, Gress DM, Byrd DR & Winchester DP. The eighth edition AJCC cancer staging manual: continuing to build a bridge from a population-based to a more "personalized" approach to cancer staging. CA: A Cancer Journal for Clinicians 2017 67 93-99. (https://doi.org/10.3322/caac.21388)
Tuttle RM, Tala H, Shah J, Leboeuf R, Ghossein R, Gonen M, Brokhin M, Omry G, Fagin JA & Shaha A. Estimating risk of recurrence in differentiated thyroid cancer after total thyroidectomy and radioactive iodine remnant ablation: using response to therapy variables to modify the initial risk estimates predicted by the new american thyroid associations. Thyroid 2010 20 1341-1349. (https://doi.org/10.1089/thy.2010.0178)
Momesso DP, Vaisman F, Yang SP, Bulzico DA, Corbo R, Vaisman M & Tuttle RM. Dynamic risk stratification in patients with differentiated thyroid cancer treated without radioactive iodine. Journal of Clinical Endocrinology and Metabolism 2016 101 2692-2700. (https://doi.org/10.1210/jc.2015-4290)
Dufour P, Pirard C, Seghaye MC & Charlier C. Association between organohalogenated pollutants in cord blood and thyroid function in newborns and mothers from Belgian population. Environmental Pollution 2018 238 389-396. (https://doi. org/10.1016/j.envpol.2018.03.058)
Pirard C, Dufour P & Charlier C. Background contamination of perfluoralkyl substances in a Belgian general population. Toxicology Letters 2020 333 13-21. (https://doi.org/10.1016/j.toxlet.2020.07.015)
Pirard C & Charlier C. Simple and fast method for the measurement of legacy and novel brominated flame retardants in human serum. Chemosphere 2018 211 918-925. (https://doi. org/10.1016/j.chemosphere.2018.08.012)
Phillips DL, Pirkle JL, Burse VW, Bernert JTJ, Henderson LO & Needham LL. Chlorinated hydrocarbon levels in human serum: effects of fasting and feeding. Archives of Environmental Contamination and Toxicology 1989 18 495-500. (https://doi. org/10.1007/BF01055015)
Fugazzola L, Mannavola D, Cirello V, Vannucchi G, Muzza M, Vicentini L & Beck-Peccoz P. BRAF mutations in an Italian cohort of thyroid cancers. Clinical Endocrinology 2004 61 239-243. (https:// doi.org/10.1111/j.1365-2265.2004.02089.x)
Steenland K & Winquist A. PFAS and cancer, a scoping review of the epidemiologic evidence. Environmental Research 2021 194 110690. (https://doi.org/10.1016/j.envres.2020.110690)
Papadopoulou E, Nicolescu A, Haug LS, Husøy T, Deleanu C, Dirven H & Lindeman B. Lipoprotein profiles associated with exposure to poly- and perfluoroalkyl substances (PFASs) in the EuroMix human biomonitoring study. Environmental Pollution 2022 308 119664. (https://doi.org/10.1016/j.envpol.2022.119664)
Mrema EJ, Rubino FM, Mandic-Rajcevic S, Sturchio E, Turci R, Osculati A, Brambilla G, Minoia C & Colosio C. Exposure to priority organochlorine contaminants in the Italian general population. Part 2: fifteen priority polychlorinated biphenyl congeners in blood serum. Human and Experimental Toxicology 2014 33 170-184. (https://doi.org/10.1177/0960327113485256)
Li X, Song F, Liu X, Shan A, Huang Y, Yang Z, Li H, Yang Q, Yu Y, Zheng H, et al. Perfluoroalkyl substances (PFASs) as risk factors for breast cancer: a case-control study in Chinese population. Environmental Health 2022 21 83. (https://doi.org/10.1186/s12940- 022-00895-3)
Velarde MC, Chan AFO, Sajo MEJV, Zakharevich I, Melamed J, Uy GLB, Teves JMY, Corachea AJM, Valparaiso AP, Macalindong SS, et al. Elevated levels of perfluoroalkyl substances in breast cancer patients within the Greater Manila Area. Chemosphere 2022 286 131545. (https://doi.org/10.1016/j.chemosphere.2021.131545)
Xu M, Zhang T, Lv C, Niu Q, Zong W, Tang J & Liu R. Perfluorodecanoic acid-induced oxidative stress and DNA damage investigated at the cellular and molecular levels. Ecotoxicology and Environmental Safety 2019 185 109699. (https://doi.org/10.1016/j. ecoenv.2019.109699)
Gao S, Jing M, Xu M, Han D, Niu Q & Liu R. Cytotoxicity of perfluorodecanoic acid on mouse primary nephrocytes through oxidative stress: combined analysis at cellular and molecular levels. Journal of Hazardous Materials 2020 393 122444. (https://doi. org/10.1016/j.jhazmat.2020.122444)
Deng SZ, Xu CL, Xu ZF, Zhou LY, Xie SJ, Wei KN, Jin YC, Zeng ZC, Yang XJ, Tan SH, et al. Perfluorodecanoic acid induces meiotic defects and deterioration of mice oocytes in vitro. Toxicology 2021 460 152884. (https://doi.org/10.1016/j.tox.2021.152884)
Ameziane El Hassani R, Buffet C, Leboulleux S & Dupuy C. Oxidative stress in thyroid carcinomas: biological and clinical significance. Endocrine-Related Cancer 2019 26 R131-R143. (https:// doi.org/10.1530/ERC-18-0476)
Dong T, Peng Y, Zhong N, Liu F, Zhang H, Xu M, Liu R, Han M, Tian X, Jia J, et al. Perfluorodecanoic acid (PFDA) promotes gastric cell proliferation via sPLA2-IIA. Oncotarget 2017 8 50911-50920. (https://doi.org/10.18632/oncotarget.17284)
Deziel NC, Warren JL, Huang H, Zhou H, Sjodin A & Zhang Y. Exposure to polychlorinated biphenyls and organochlorine pesticides and thyroid cancer in connecticut women. Environmental Research 2021 192 110333. (https://doi.org/10.1016/j. envres.2020.110333)
Dufour P, Pirard C, Petrossians P, Beckers A & Charlier C. Association between mixture of persistent organic pollutants and thyroid pathologies in a Belgian population. Environmental Research 2020 181 108922. (https://doi.org/10.1016/j. envres.2019.108922)
Derakhshan A, Kortenkamp A, Shu H, Broeren MAC, Lindh CH, Peeters RP, Bornehag CG, Demeneix B & Korevaar TIM. Association of per- and polyfluoroalkyl substances with thyroid homeostasis during pregnancy in the SELMA study. Environment International 2022 167 107420. (https://doi.org/10.1016/j.envint.2022.107420)
Berg V, Nøst TH, Hansen S, Elverland A, Veyhe AS, Jorde R, Odland JØ & Sandanger TM. Assessing the relationship between perfluoroalkyl substances, thyroid hormones and binding proteins in pregnant women; a longitudinal mixed effects approach. Environment International 2015 77 63-69. (https://doi.org/10.1016/j. envint.2015.01.007)
Wang Y, Rogan WJ, Chen PC, Lien GW, Chen HY, Tseng YC, Longnecker MP & Wang SL. Association between maternal serum perfluoroalkyl substances during pregnancy and maternal and cord thyroid hormones: Taiwan maternal and infant cohort study. Environmental Health Perspectives 2014 122 529-534. (https://doi. org/10.1289/ehp.1306925)
Blake BE, Pinney SM, Hines EP, Fenton SE & Ferguson KK. Associations between longitudinal serum perfluoroalkyl substance (PFAS) levels and measures of thyroid hormone, kidney function, and body mass index in the fernald community cohort. Environmental Pollution 2018 242 894-904. (https://doi. org/10.1016/j.envpol.2018.07.042)
Song M, Kim YJ, Park YK & Ryu JC. Changes in thyroid peroxidase activity in response to various chemicals. Journal of Environmental Monitoring 2012 14 2121-2126. (https://doi.org/10.1039/ c2em30106g)
Chen PP, Yang P, Liu C, Deng YL, Luo Q, Miao Y, Zhang M, Cui FP, Zeng JY, Shi T, et al. Urinary concentrations of phenols, oxidative stress biomarkers and thyroid cancer: exploring associations and mediation effects. Journal of Environmental Sciences 2022 120 30-40. (https://doi.org/10.1016/j.jes.2022.01.009)
