Abstract
Papillary thyroid cancer (PTC) has inflicted huge threats to the health of mankind. Metal pollution could be a potential risk factor of PTC occurrence, but existing relevant epidemiological researches are limited. The current case-control study was designed to evaluate the relationships between exposure to multiple metals and the risk of PTC. A total of 262 histologically confirmed PTC cases were recruited. Age- and gender-matched controls were enrolled at the same time. Urine samples were used as biomarkers to reflect the levels of environmental exposure to 13 metals. Conditional logistic regression models were adopted to assess the potential association. Single-metal and multi-metal models were separately conducted to evaluate the impacts of single and co-exposure to 13 metals. The increased concentration of urinary Cd, Cu, Fe, and Pb quartiles was found significant correlated with PTC risk. We also found the decreased trends of urinary Se, Zn, and Mn quartiles with the ORs for PTC. These dose-response associations between Pb and PTC were observed in the single-metal model and remained significant in the multi-metal model (OR25-50th=1.39, OR50-75th=3.32, OR>75th=7.62, p for trend <0.001). Our study suggested that PTC was positively associated with urinary levels of Cd, Cu, Fe, Pb, and inversely associated with Se, Zn, and Mn. Targeted public health policies should be made to improve the environment and the recognition of potential risk factors. These findings need additional studies to confirm in other population.
Similar content being viewed by others
References
Afrifa J, Ogbordjor WD, Duku-Takyi R (2018) Variation in thyroid hormone levels is associated with elevated blood mercury levels among artisanal small-scale miners in Ghana. PLoS One 13:e0203335. https://doi.org/10.1371/journal.pone.0203335
Almquist M, Johansen D, Björge T, Ulmer H, Lindkvist B, Stocks T, Hallmans G, Engeland A, Rapp K, Jonsson H, Selmer R, Diem G, Häggström C, Tretli S, Stattin P, Manjer J (2011) Metabolic factors and risk of thyroid cancer in the metabolic syndrome and Cancer project (Me-Can). Cancer Causes Control : CCC 22:743–751. https://doi.org/10.1007/s10552-011-9747-2
Benbrahim-Tallaa L, Tokar EJ, Diwan BA, Dill AL, Coppin JF, Waalkes MP (2009) Cadmium malignantly transforms normal human breast epithelial cells into a basal-like phenotype. Environ Health Perspect 117:1847–1852. https://doi.org/10.1289/ehp.0900999
Buha A, Matovic V, Antonijevic B, Bulat Z, Curcic M, Renieri E, Tsatsakis A, Schweitzer A, Wallace D (2018) Overview of cadmium thyroid disrupting effects and mechanisms. Int J Mol Sci 19. https://doi.org/10.3390/ijms19051501
Castaño A, Sánchez-Rodríguez JE, Cañas A, Esteban M, Navarro C, Rodríguez-García AC, Arribas M, Díaz G, Jiménez-Guerrero JA (2012) Mercury, lead and cadmium levels in the urine of 170 Spanish adults: a pilot human biomonitoring study. Int J Hyg Environ Health 215:191–195. https://doi.org/10.1016/j.ijheh.2011.09.001
Cho YA, Kim J (2014) Thyroid cancer risk and smoking status: a meta-analysis. Cancer causes & control : CCC 25:1187–1195. https://doi.org/10.1007/s10552-014-0422-2
Cho A, Chang Y, Ahn J, Shin H, Ryu S (2018) Cigarette smoking and thyroid cancer risk: a cohort study. Br J Cancer 119:638–645. https://doi.org/10.1038/s41416-018-0224-5
Choi W, Kim S, Baek YW, Choi K, Lee K, Kim S, Yu SD, Choi K (2017) Exposure to environmental chemicals among Korean adults—updates from the second Korean National Environmental Health Survey (2012–2014). Int J Hyg Environ Health 220:29–35. https://doi.org/10.1016/j.ijheh.2016.10.002
Cui Y, Zhong Q, Hu M, Sheng J, Yang Y, Liang L, Wang X, Yang Y, Zhou M, Huang F (2017) Human biomonitoring of eight trace elements in urine of residents living in rural areas along the Yangtze River. China Environ Sci Pollut Res Int 24:27963–27973. https://doi.org/10.1007/s11356-017-0414-3
Duntas LH (2010) Selenium and the thyroid: a close-knit connection. J Clin Endocr Metab 95:5180–5188. https://doi.org/10.1210/jc.2010-0191
Eder K, Kralik A, Kirchgessner M (1996) The effect of manganese supply on thyroid hormone metabolism in the offspring of manganese-depleted dams. Biol Trace Elem Res 55:137–145. https://doi.org/10.1007/bf02784175
Eftekhari MH, Keshavarz SA, Jalali M, Elguero E, Eshraghian MR, Simondon KB (2006) The relationship between iron status and thyroid hormone concentration in iron-deficient adolescent Iranian girls. Asia Pac J Clin Nutr 15:50–55
Emami A, Nazem MR, Shekarriz R, Hedayati M (2017) Micronutrient status (calcium, zinc, vitamins D and E) in patients with medullary thyroid carcinoma: a cross-sectional study. Nutrition 41:86–89. https://doi.org/10.1016/j.nut.2017.04.004
Hammouda F, Messaoudi I, El Hani J, Baati T, Saïd K, Kerkeni A (2008) Reversal of cadmium-induced thyroid dysfunction by selenium, zinc, or their combination in rat. Biol Trace Elem Res 126:194–203. https://doi.org/10.1007/s12011-008-8194-8
Hata A, Endo Y, Nakajima Y, Ikebe M, Ogawa M, Fujitani N, Endo G (2007) HPLC-ICP-MS speciation analysis of arsenic in urine of Japanese subjects without occupational exposure. J Occup Health 49:217–223. https://doi.org/10.1539/joh.49.217
Itoh H, Iwasaki M, Sawada N, Takachi R, Kasuga Y, Yokoyama S, Onuma H, Nishimura H, Kusama R, Yokoyama K, Tsugane S (2014) Dietary cadmium intake and breast cancer risk in Japanese women: a case-control study. Int J Hyg Environ Health 217:70–77. https://doi.org/10.1016/j.ijheh.2013.03.010
Jain RB (2014) Thyroid function and serum copper, selenium, and zinc in general U.S. population. Biol Trace Elem Res 159:87–98. https://doi.org/10.1007/s12011-014-9992-9
Jancic SA, Stosic BZ (2014) Cadmium effects on the thyroid gland. Vitam Horm 94:391–425. https://doi.org/10.1016/B978-0-12-800095-3.00014-6
Khatiwada S, Gelal B, Baral N, Lamsal M (2016) Association between iron status and thyroid function in Nepalese children. Thyroid Res 9:2–2. https://doi.org/10.1186/s13044-016-0031-0
Khlifi R, Hamza-Chaffai A (2010) Head and neck cancer due to heavy metal exposure via tobacco smoking and professional exposure: a review. Toxicol Appl Pharmacol 248:71–88. https://doi.org/10.1016/j.taap.2010.08.003
Kilfoy BA, Zheng T, Holford TR, Han X, Ward MH, Sjodin A, Zhang Y, Bai Y, Zhu C, Guo GL, Rothman N, Zhang Y (2009) International patterns and trends in thyroid cancer incidence, 1973-2002. Cancer Causes Control : CCC 20:525–531. https://doi.org/10.1007/s10552-008-9260-4
Kilic E, Saraymen R, Demiroglu A, Ok E (2004) Chromium and manganese levels in the scalp hair of normals and patients with breast cancer. Biol Trace Elem Res 102:19–25. https://doi.org/10.1385/Bter:102:1-3:019
Kim NH, Hyun YY, Lee KB (2015) Environmental heavy metal exposure and chronic kidney disease in the general population. J Korean Med Sci 30:272–277. https://doi.org/10.3346/jkms.2015.30.3.272
Kohrle J, Gartner R (2009) Selenium and thyroid. Best Pract Res Cl En 23:815–827. https://doi.org/10.1016/j.beem.2009.08.002
Kucharzewski M, Braziewicz J, Majewska U, Gozdz S (2003) Copper, zinc, and selenium in whole blood and thyroid tissue of people with various thyroid diseases. Biol Trace Elem Res 93:9–18. https://doi.org/10.1385/bter:93:1-3:9
Leux C, Truong T, Petit C, Baron-Dubourdieu D, Guenel P (2012) Family history of malignant and benign thyroid diseases and risk of thyroid cancer: a population-based case-control study in New Caledonia. Cancer Causes Control : CCC 23:745–755. https://doi.org/10.1007/s10552-012-9944-7
Lim H, Devesa SS, Sosa JA, Check D, Kitahara CM (2017) Trends in thyroid cancer incidence and mortality in the United States, 1974-2013. Jama 317:1338–1348. https://doi.org/10.1001/jama.2017.2719
López CM, Piñeiro AE, Núñez N, Avagnina AM, Villaamil EC, Roses OE (2000) Thyroid hormone changes in males exposed to lead in the Buenos Aires area (Argentina). Pharmacol Res 42:599–602. https://doi.org/10.1006/phrs.2000.0734
Luca E, Fici L, Ronchi A, Marandino F, Rossi ED, Caristo ME, Malandrino P, Russo M, Pontecorvi A, Vigneri R, Moretti F (2017) Intake of boron, cadmium, and molybdenum enhances rat thyroid cell transformation. J Exp Clin Cancer Res: CR 36:73. https://doi.org/10.1186/s13046-017-0543-z
Malandrino P, Russo M, Ronchi A, Minoia C, Cataldo D, Regalbuto C, Giordano C, Attard M, Squatrito S, Trimarchi F, Vigneri R (2016) Increased thyroid cancer incidence in a basaltic volcanic area is associated with non-anthropogenic pollution and biocontamination. Endocrine 53:471–479. https://doi.org/10.1007/s12020-015-0761-0
Mitrunen K, Sillanpää P, Kataja V, Eskelinen M, Kosma VM, Benhamou S, Uusitupa M, Hirvonen A (2001) Association between manganese superoxide dismutase (MnSOD) gene polymorphism and breast cancer risk. Carcinogenesis 22:827–829. https://doi.org/10.1093/carcin/22.5.827
Mittag J, Behrends T, Nordstrom K, Anselmo J, Vennstrom B, Schomburg L (2012) Serum copper as a novel biomarker for resistance to thyroid hormone. Biochem J 443:103–109. https://doi.org/10.1042/bj20111817
O'Grady TJ, Kitahara CM, DiRienzo AG, Gates MA (2014) The association between selenium and other micronutrients and thyroid cancer incidence in the NIH-AARP diet and health study. PLoS One 9:e110886. https://doi.org/10.1371/journal.pone.0110886
Pollán M, Gustavsson P (1999) High-risk occupations for breast cancer in the Swedish female working population. Am J Public Health 89:875–881
Quandt SA, Jones BT, Talton JW, Whalley LE, Galván L, Vallejos QM, Grzywacz JG, Chen H, Pharr KE, Isom S, Arcury TA (2010) Heavy metals exposures among Mexican farmworkers in eastern North Carolina. Environ Res 110:83–88. https://doi.org/10.1016/j.envres.2009.09.007
Rago T, Fiore E, Scutari M, Santini F, di Coscio G, Romani R, Piaggi P, Ugolini C, Basolo F, Miccoli P, Pinchera A, Vitti P (2010) Male sex, single nodularity, and young age are associated with the risk of finding a papillary thyroid cancer on fine-needle aspiration cytology in a large series of patients with nodular thyroid disease. Eur J Endocrinol 162:763–770. https://doi.org/10.1530/eje-09-0895
Rana SVS (2014) Perspectives in endocrine toxicity of heavy metals—a review. Biol Trace Elem Res 160:1–14. https://doi.org/10.1007/s12011-014-0023-7
Rokadia HK, Agarwal S (2013) Serum heavy metals and obstructive lung disease: results from the National Health and nutrition. Examination Survey. Chest 143:388–397. https://doi.org/10.1378/chest.12-0595
Sanabria A, Kowalski LP, Shah JP, Nixon IJ (2018) Growing incidence of thyroid carcinoma in recent years: factors underlying overdiagnosis. Head Neck 40:855–866. https://doi.org/10.1002/hed.25029
Schomburg L, Kohrle J (2008) On the importance of selenium and iodine metabolism for thyroid hormone biosynthesis and human health. Mol Nutr Food Res 52:1235–1246. https://doi.org/10.1002/mnfr.200700465
Shen F, Cai WS, Li JL, Feng Z, Cao J, Xu B (2015) The association between serum levels of selenium, copper, and magnesium with thyroid cancer: a meta-analysis. Biol Trace Elem Res 167:225–235. https://doi.org/10.1007/s12011-015-0304-9
Siegel RL, Miller KD, Jemal A (2018) Cancer statistics, 2018. CA Cancer J Clin 68:7–30. https://doi.org/10.3322/caac.21442
Sun YL, Li YW, Liu ZH, Chen QL (2018) Environmentally relevant concentrations of mercury exposure alter thyroid hormone levels and gene expression in the hypothalamic-pituitary-thyroid axis of zebrafish larvae fish. Physiol Biochem 44:1175–1183. https://doi.org/10.1007/s10695-018-0504-2
Taylor AJ, Croft AP, Palace AM, Winter DL, Reulen RC, Stiller CA, Stevens MCG, Hawkins MM (2009) Risk of thyroid cancer in survivors of childhood cancer: results from the British childhood Cancer survivor study. Int J Cancer 125:2400–2405. https://doi.org/10.1002/ijc.24581
Vye ZTAF, Vtyurin BM (1995) Trace Elements and Thyroid Cancer. Analyst 120:817
Wang Y, Wang W (2015) Increasing incidence of thyroid cancer in Shanghai, China, 1983-2007. Asia-Pac J Public Health 27:Np223–Np229. https://doi.org/10.1177/1010539512436874
Wu W, Jiang S, Zhao Q, Zhang K, Wei X, Zhou T, Liu D, Zhou H, Zhong R, Zeng Q, Cheng L, Miao X, Lu Q (2018) Associations of environmental exposure to metals with the risk of hypertension in China. Sci Total Environ 622-623:184–191. https://doi.org/10.1016/j.scitotenv.2017.11.343
Xu SQ, Ying J, Jiang B, Guo W, Adachi T, Sharov V, Lazar H, Menzoian J, Knyushko TV, Bigelow D, Schöneich C, Cohen RA (2006) Detection of sequence-specific tyrosine nitration of manganese SOD and SERCA in cardiovascular disease and aging. Am J Physiol-Heart C 290:H2220–H2227. https://doi.org/10.1152/ajpheart.01293.2005
Yavuz O, Yavuz T, Kahraman C, Yesildal N, Bundak R (2004) The relationship between iron status and thyroid hormones in adolescents living in an iodine deficient area. J Pediatr Endocrinol Metab 17. https://doi.org/10.1515/JPEM.2004.17.10.1443
Zimeri AM, Robb SW, Hassan SM, Hire RR, Davis MB (2015) Assessing heavy metal and PCB exposure from tap water by measuring levels in plasma from sporadic breast cancer patients, a pilot study. Int J Environ Res Public Health 12:15683–15691. https://doi.org/10.3390/ijerph121215013
Acknowledgements
This work was supported by National Natural Science Foundation of China (No. 81373071) and the Project for Anhui Province Academic Technology Leader Reserve Candidates’ Academic Research Activities (2017H108).
Author information
Authors and Affiliations
Corresponding authors
Ethics declarations
Ethical approval
All procedures performed in studies involving human participants were in accordance with the ethical standards of the Anhui Medical University Biomedical Ethics Committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.
Conflict of interest
The authors declare that they have no conflict of interest.
Informed consent
Informed consent was obtained from all individual participants included in the study.
Additional information
Responsible editor: Philippe Garrigues
Publisher’s note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
About this article
Cite this article
Zhang, C., Wu, HB., Cheng, MX. et al. Association of exposure to multiple metals with papillary thyroid cancer risk in China. Environ Sci Pollut Res 26, 20560–20572 (2019). https://doi.org/10.1007/s11356-019-04733-x
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11356-019-04733-x