Abstract
Parabens are widely used as preservatives, which have been found to affect thyroid function in toxicological studies. However, population studies on whether they are associated with thyroid tumors remain unclear. This study aims to investigate the relationship between environmental paraben exposure and thyroid cancer and benign nodules. We recruited participants from the Department of Thyroid and Breast Surgery at Wuhan Central Hospital, Wuhan, China. The detectable percentages of methyl paraben, ethyl paraben, and propyl paraben in the urinary samples of 425 study subjects were 99.1%, 95.3%, and 92.0%, respectively. All uncorrected and creatinine-corrected parabens were moderately correlated with one another. After adjusting for possible confounders, all three parabens were associated with an increased risk of thyroid cancer. Furthermore, the mixture pollutant analysis of parabens found positive associations with risk of thyroid cancer (OR = 0.24, 95% CI: 0.18, 0.31) and benign nodules (OR = 1.33, 95% CI: 0.86, 1.80). We observed that individual exposure to paraben mixtures may be associated with the risk of thyroid cancer and benign nodules.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
Data availability
All data are mentioned in the body of manuscript, tables, and figure.
References
Aker AM, Ferguson KK, Rosario ZY, Mukherjee B, Alshawabkeh AN, Calafat AM, Cordero JF, Meeker JD (2019) A repeated measures study of phenol, paraben and Triclocarban urinary biomarkers and circulating maternal hormones during gestation in the Puerto Rico PROTECT cohort. Environ Health 18:28. https://doi.org/10.1186/s12940-019-0459-5
Aker AM, Johns L, McElrath TF, Cantonwine DE, Mukherjee B, Meeker JD (2018) Associations between maternal phenol and paraben urinary biomarkers and maternal hormones during pregnancy: a repeated measures study. Environ Int 113:341–349. https://doi.org/10.1016/j.envint.2018.01.006
Aschebrook-Kilfoy B, Grogan RH, Ward MH, Kaplan E, Devesa SS (2013) Follicular thyroid cancer incidence patterns in the United States, 1980–2009. Thyroid 23:1015–1021. https://doi.org/10.1089/thy.2012.0356
Asimakopoulos AG, Thomaidis NS, Kannan K (2014) Widespread occurrence of bisphenol A diglycidyl ethers, p-hydroxybenzoic acid esters (parabens), benzophenone type-UV filters, triclosan, and triclocarban in human urine from Athens, Greece. Sci Total Environ 470–471:1243–1249. https://doi.org/10.1016/j.scitotenv.2013.10.089
Asimakopoulos AG, Xue J, De Carvalho BP, Iyer A, Abualnaja KO, Yaghmoor SS, Kumosani TA, Kannan K (2016) Urinary biomarkers of exposure to 57 xenobiotics and its association with oxidative stress in a population in Jeddah, Saudi Arabia. Environ Res 150:573–581. https://doi.org/10.1016/j.envres.2015.11.029
Au AY, McBride C, Wilhelm KG Jr, Koenig RJ, Speller B, Cheung L, Messina M, Wentworth J, Tasevski V, Learoyd D, Robinson BG, Clifton-Bligh RJ (2006) PAX8-peroxisome proliferator-activated receptor gamma (PPARgamma) disrupts normal PAX8 or PPARgamma transcriptional function and stimulates follicular thyroid cell growth. Endocrinology 147:367–376. https://doi.org/10.1210/en.2005-0147
Baker BH, Wu H, Laue HE, Boivin A, Gillet V, Langlois MF, Bellenger JP, Baccarelli AA, Takser L (2020) Methylparaben in meconium and risk of maternal thyroid dysfunction, adverse birth outcomes, and attention-deficit hyperactivity disorder (ADHD). Environ Int 139: 105716. https://doi.org/10.1016/j.envint.2020.105716
Bernal J (2007) Thyroid hormone receptors in brain development and function. Nat Clin Pract Endocrinol Metab 3:249–259. https://doi.org/10.1038/ncpendmet0424
Błędzka D, Gromadzińska J, Wąsowicz W (2014) Parabens. From environmental studies to human health. Environ Int 67:27–42. https://doi.org/10.1016/j.envint.2014.02.007
Brinton LA, Sakoda LC, Frederiksen K, Sherman ME, Kjaer SK, Graubard BI, Olsen JH, Mellemkjaer L (2007) Relationships of uterine and ovarian tumors to pre-existing chronic conditions. Gynecol Oncol 107:487–494. https://doi.org/10.1016/j.ygyno.2007.08.002
Calafat AM, Weuve J, Ye X, Jia LT, Hu H, Ringer S, Huttner K, Hauser R (2009) Exposure to bisphenol A and other phenols in neonatal intensive care unit premature infants. Environ Health Perspect 117:639–644. https://doi.org/10.1289/ehp.0800265
Calafat AM, Ye X, Wong LY, Bishop AM, Needham LL (2010) Urinary concentrations of four parabens in the U.S. population: NHANES 2005–2006. Environ Health Perspect 118:679–685. https://doi.org/10.1289/ehp.0901560
Cheng F, Xiao J, Shao C, Huang F, Wang L, Ju Y, Jia H (2021) Burden of thyroid cancer from 1990 to 2019 and projections of incidence and mortality until 2039 in China: findings from Global Burden of Disease Study. Front Endocrinol (lausanne) 12:738213. https://doi.org/10.3389/fendo.2021.738213
Darbre PD, Harvey PW (2008) Paraben esters: review of recent studies of endocrine toxicity, absorption, esterase and human exposure, and discussion of potential human health risks. J Appl Toxicol 28:561–578. https://doi.org/10.1002/jat.1358
Davis PJ, Mousa SA, Lin HY (2021) Nongenomic actions of thyroid hormone: the integrin component. Physiol Rev 101:319–352. https://doi.org/10.1152/physrev.00038.2019
Delfosse V, Maire AL, Balaguer P, Bourguet W (2015) A structural perspective on nuclear receptors as targets of environmental compounds. Acta Pharmacol Sin 36:88–101. https://doi.org/10.1038/aps.2014.133
Dewalque L, Pirard C, Charlier C (2014) Measurement of urinary biomarkers of parabens, benzophenone-3, and phthalates in a Belgian population. Biomed Res Int 2014:649314. https://doi.org/10.1155/2014/649314
Engel LS, Buckley JP, Yang G, Liao LM, Satagopan J, Calafat AM, Matthews CE, Cai Q, Ji BT, Cai H, Engel SM, Wolff MS, Rothman N, Zheng W, Xiang YB, Shu XO, Gao YT, Chow WH (2014) Predictors and variability of repeat measurements of urinary phenols and parabens in a cohort of Shanghai women and men. Environ Health Perspect 122:733–740. https://doi.org/10.1289/ehp.1306830
Franco AT, Malaguarnera R, Refetoff S, Liao XH, Lundsmith E, Kimura S, Pritchard C, Marais R, Davies TF, Weinstein LS, Chen M, Rosen N, Ghossein R, Knauf JA, Fagin JA (2011) Thyrotrophin receptor signaling dependence of Braf-induced thyroid tumor initiation in mice. Proc Natl Acad Sci U S A 108:1615–1620. https://doi.org/10.1073/pnas.1015557108
Gaberšček S, Zaletel K (2011) Thyroid physiology and autoimmunity in pregnancy and after delivery. Expert Rev Clin Immunol 7: 697–706; quiz 707. https://doi.org/10.1586/eci.11.42
Gao Y, Qu N, Zhang L, Chen JY, Ji QH (2016) Preoperative ultrasonography and serum thyroid-stimulating hormone on predicting central lymph node metastasis in thyroid nodules as or suspicious for papillary thyroid microcarcinoma. Tumour Biol 37:7453–7459. https://doi.org/10.1007/s13277-015-4535-3
Genuis SJ, Birkholz D, Curtis L, Sandau C (2013) Paraben levels in an urban community of Western Canada. ISRN Toxicol 2013:507897. https://doi.org/10.1155/2013/507897
Gore AC, Chappell VA, Fenton SE, Flaws JA, Nadal A, Prins GS, Toppari J, Zoeller RT (2015) EDC-2: The Endocrine Society’s second scientific statement on endocrine-disrupting chemicals. Endocr Rev 36:E1-e150. https://doi.org/10.1210/er.2015-1010
Greenland S (1989) Modeling and variable selection in epidemiologic analysis. Am J Public Health 79:340–349. https://doi.org/10.2105/ajph.79.3.340
Gudmundsson J et al (2012) Discovery of common variants associated with low TSH levels and thyroid cancer risk. Nat Genet 44:319–322. https://doi.org/10.1038/ng.1046
Guo Y, Kannan K (2013) A survey of phthalates and parabens in personal care products from the United States and its implications for human exposure. Environ Sci Technol 47:14442–14449. https://doi.org/10.1021/es4042034
Haman C, Dauchy X, Rosin C, Munoz JF (2015) Occurrence, fate and behavior of parabens in aquatic environments: a review. Water Res 68:1–11. https://doi.org/10.1016/j.watres.2014.09.030
Hoffman K, Lorenzo A, Butt CM, Hammel SC, Henderson BB, Roman SA, Scheri RP, Stapleton HM, Sosa JA (2017) Exposure to flame retardant chemicals and occurrence and severity of papillary thyroid cancer: a case-control study. Environ Int 107:235–242. https://doi.org/10.1016/j.envint.2017.06.021
Huang H, Rusiecki J, Udelsman R, Zhang Y (2018) TSH, thyroid hormone, and PTC-response. Cancer Epidemiol Biomarkers Prev 27:228–229. https://doi.org/10.1158/1055-9965.epi-17-0806
Huang H, Rusiecki J, Zhao N, Chen Y, Ma S, Yu H, Ward MH, Udelsman R, Zhang Y (2017) Thyroid-stimulating hormone, thyroid hormones, and risk of papillary thyroid cancer: a nested case-control study. Cancer Epidemiol Biomarkers Prev 26:1209–1218. https://doi.org/10.1158/1055-9965.epi-16-0845
Jakopin Ž (2021) Assessment of the endocrine-disrupting potential of halogenated parabens: an in silico approach. Chemosphere 264:128447. https://doi.org/10.1016/j.chemosphere.2020.128447
Janjua NR, Frederiksen H, Skakkebaek NE, Wulf HC, Andersson AM (2008) Urinary excretion of phthalates and paraben after repeated whole-body topical application in humans. Int J Androl 31:118–130. https://doi.org/10.1111/j.1365-2605.2007.00841.x
Keil AP, Buckley JP, O’Brien KM, Ferguson KK, Zhao S, White AJ (2020) A quantile-based g-computation approach to addressing the effects of exposure mixtures. Environ Health Perspect 128:47004. https://doi.org/10.1289/ehp5838
Kiani Feizabadi G, Hajizadeh Y, Feizi A, Ebrahimpour K (2020) Urinary concentrations of parabens amongst Iranian adults and their associations with socio-demographic factors. J Environ Health Sci Eng 18:1227–1238. https://doi.org/10.1007/s40201-020-00540-6
Kim J, Gosnell JE, Roman SA (2020) Geographic influences in the global rise of thyroid cancer. Nat Rev Endocrinol 16:17–29. https://doi.org/10.1038/s41574-019-0263-x
Koeppe ES, Ferguson KK, Colacino JA, Meeker JD (2013) Relationship between urinary triclosan and paraben concentrations and serum thyroid measures in NHANES 2007–2008. Sci Total Environ 445–446:299–305. https://doi.org/10.1016/j.scitotenv.2012.12.052
Langer P (2008) Persistent organochlorinated pollutants (PCB, DDE, HCB, dioxins, furans) and the thyroid–review 2008. Endocr Regul 42:79–104
Li J, Liu W, Xia W, Zhao H, Zhou Y, Li Y, Wu C, Liu H, Zhang B, Zhu Y, Hu J, Wang X, Ye D, Xu S, Cai Z (2019) Variations, determinants, and coexposure patterns of personal care product chemicals among chinese pregnant women: a longitudinal study. Environ Sci Technol 53:6546–6555. https://doi.org/10.1021/acs.est.9b01562
Li W, Gao L, Shi Y, Wang Y, Liu J, Cai Y (2016a) Spatial distribution, temporal variation and risks of parabens and their chlorinated derivatives in urban surface water in Beijing, China. Sci Total Environ 539:262–270. https://doi.org/10.1016/j.scitotenv.2015.08.150
Li Z, Wang B, Ge S, Yan L, Liu Y, Li Z, Ren A (2016b) A simultaneous analysis method of polycyclic aromatic hydrocarbons, nicotine, cotinine and metals in human hair. Environ Pollut 219:66–71. https://doi.org/10.1016/j.envpol.2016.09.045
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
Lim S (2020) The associations between personal care products use and urinary concentrations of phthalates, parabens, and triclosan in various age groups: The Korean National Environmental Health Survey Cycle 3 2015–2017. Sci Total Environ 742:140640. https://doi.org/10.1016/j.scitotenv.2020.140640
Lin HY, Chin YT, Yang YC, Lai HY, Wang-Peng J, Liu LF, Tang HY, Davis PJ (2016) Thyroid hormone, cancer, and apoptosis. Compr Physiol 6:1221–1237. https://doi.org/10.1002/cphy.c150035
Lin YH, Wu MH, Liao CJ, Huang YH, Chi HC, Wu SM, Chen CY, Tseng YH, Tsai CY, Chung IH, Tsai MM, Chen CY, Lin TP, Yeh YH, Chen WJ, Lin KH (2015) Repression of microRNA-130b by thyroid hormone enhances cell motility. J Hepatol 62:1328–1340. https://doi.org/10.1016/j.jhep.2014.12.035
Liu TR, Su X, Qiu WS, Chen WC, Men QQ, Zou L, Li ZQ, Fu XY, Yang AK (2016) Thyroid-stimulating hormone receptor affects metastasis and prognosis in papillary thyroid carcinoma. Eur Rev Med Pharmacol Sci 20:3582–3591
Liu X, Chen D, Wang B, Xu F, Pang Y, Zhang L, Zhang Y, Jin L, Li Z, Ren A (2020) Does low maternal exposure to per- and polyfluoroalkyl substances elevate the risk of spontaneous preterm birth? A nested case-control study in China. Environ Sci Technol 54:8259–8268. https://doi.org/10.1021/acs.est.0c01930
Liu X, Peng C, Shi Y, Tan H, Tang S, Chen D (2019) Beyond phthalate diesters: existence of phthalate monoesters in South China house dust and implications for human exposure. Environ Sci Technol 53:11675–11683. https://doi.org/10.1021/acs.est.9b03817
Lu S, Ren L, Liu Y, Ma H, Liu S, Zhu Z, Tang Z, Kang L, Liao S (2019) Urinary parabens in children from South China: implications for human exposure and health risks. Environ Pollut 254:113007. https://doi.org/10.1016/j.envpol.2019.113007
Ma WL, Wang L, Guo Y, Liu LY, Qi H, Zhu NZ, Gao CJ, Li YF, Kannan K (2013) Urinary concentrations of parabens in Chinese young adults: implications for human exposure. Arch Environ Contam Toxicol 65:611–618. https://doi.org/10.1007/s00244-013-9924-2
Meeker JD, Yang T, Ye X, Calafat AM, Hauser R (2011) Urinary concentrations of parabens and serum hormone levels, semen quality parameters, and sperm DNA damage. Environ Health Perspect 119:252–257. https://doi.org/10.1289/ehp.1002238
Miao H, Liu X, Li J, Zhang L, Zhao Y, Liu S, Ni S, Wu Y (2020) Associations of urinary phthalate metabolites with risk of papillary thyroid cancer. Chemosphere 241:125093. https://doi.org/10.1016/j.chemosphere.2019.125093
Moeller LC, Führer D (2013) Thyroid hormone, thyroid hormone receptors, and cancer: a clinical perspective. Endocr Relat Cancer 20:R19-29. https://doi.org/10.1530/erc-12-0219
Moos RK, Angerer J, Dierkes G, Brüning T, Koch HM (2016) Metabolism and elimination of methyl, iso- and n-butyl paraben in human urine after single oral dosage. Arch Toxicol 90: 2699–2709. https://doi.org/10.1007/s00204-015-1636-0
Noone AM, Cronin KA, Altekruse SF, Howlader N, Lewis DR, Petkov VI, Penberthy L (2017) Cancer incidence and survival trends by subtype using data from the surveillance epidemiology and end results program, 1992–2013. Cancer Epidemiol Biomarkers Prev 26:632–641. https://doi.org/10.1158/1055-9965.epi-16-0520
Pitto L, Gorini F, Bianchi F, Guzzolino E (2020) New insights into mechanisms of endocrine-disrupting chemicals in thyroid diseases: the epigenetic way. Int J Environ Res Public Health 17.https://doi.org/10.3390/ijerph17217787
Powers AE, Marcadis AR, Lee M, Morris LGT, Marti JL (2019) Changes in trends in thyroid cancer incidence in the United States, 1992 to 2016. JAMA 322:2440–2441. https://doi.org/10.1001/jama.2019.18528
Sun J, Fang R, Wang H, Xu DX, Yang J, Huang X, Cozzolino D, Fang M, Huang Y (2022) A review of environmental metabolism disrupting chemicals and effect biomarkers associating disease risks: where exposomics meets metabolomics. Environ Int 158:106941. https://doi.org/10.1016/j.envint.2021.106941
Sun Y, Li X, Benmarhnia T, Chen JC, Avila C, Sacks DA, Chiu V, Slezak J, Molitor J, Getahun D, Wu J (2021) Exposure to air pollutant mixture and gestational diabetes mellitus in Southern California: results from electronic health record data of a large pregnancy cohort. Environ Int 158:106888. https://doi.org/10.1016/j.envint.2021.106888
Vo TT, Yoo YM, Choi KC, Jeung EB (2010) Potential estrogenic effect(s) of parabens at the prepubertal stage of a postnatal female rat model. Reprod Toxicol 29:306–316. https://doi.org/10.1016/j.reprotox.2010.01.013
Wang J, Yu F, Shang Y, Ping Z, Liu L (2020) Thyroid cancer: incidence and mortality trends in China, 2005–2015. Endocrine 68:163–173. https://doi.org/10.1007/s12020-020-02207-6
Wang L, Liao C, Liu F, Wu Q, Guo Y, Moon HB, Nakata H, Kannan K (2012) Occurrence and human exposure of p-hydroxybenzoic acid esters (parabens), bisphenol A diglycidyl ether (BADGE), and their hydrolysis products in indoor dust from the United States and three East Asian countries. Environ Sci Technol 46:11584–11593. https://doi.org/10.1021/es303516u
Wang Y, Wang W (2015) Increasing incidence of thyroid cancer in Shanghai, China, 1983–2007. Asia Pac J Public Health 27: Np223–9. https://doi.org/10.1177/1010539512436874
Ward EM, Jemal A, Chen A (2010) Increasing incidence of thyroid cancer: is diagnostic scrutiny the sole explanation? Future Oncol 6:185–188. https://doi.org/10.2217/fon.09.161
Williams RR (1976) Breast and thyroid cancer and malignant melanoma promoted by alcohol-induced pituitary secretion of prolactin, T.S.H. and M.S.H. Lancet 1:996–999. https://doi.org/10.1016/s0140-6736(76)91865-1
Xie L, Wang S, Qian Y, Jia S, Wang J, Li L, Zhang W, Yu H, Bao P, Qian B (2021) Increasing gap between thyroid cancer incidence and mortality in urban Shanghai, China: an analysis spanning 43 years. Endocr Pract 27:1100–1107. https://doi.org/10.1016/j.eprac.2021.06.002
Yang P, Chen D, Wang YX, Zhang L, Huang LL, Lu WQ, Zeng Q (2020) Mediation of association between polycyclic aromatic hydrocarbon exposure and semen quality by spermatogenesis-related microRNAs: a pilot study in an infertility clinic. J Hazard Mater 384:121431. https://doi.org/10.1016/j.jhazmat.2019.121431
Ye X, Bishop AM, Reidy JA, Needham LL, Calafat AM (2006) Parabens as urinary biomarkers of exposure in humans. Environ Health Perspect 114:1843–1846. https://doi.org/10.1289/ehp.9413
Zabka TS, Fielden MR, Garrido R, Tao J, Fretland AJ, Fretland JL, Albassam MA, Singer T, Kolaja KL (2011) Characterization of xenobiotic-induced hepatocellular enzyme induction in rats: anticipated thyroid effects and unique pituitary gland findings. Toxicol Pathol 39:664–677. https://doi.org/10.1177/0192623311406934
Zeng H et al (2018) Changing cancer survival in China during 2003–15: a pooled analysis of 17 population-based cancer registries. Lancet Glob Health 6:e555–e567. https://doi.org/10.1016/s2214-109x(18)30127-x
Zorrilla LM, Gibson EK, Jeffay SC, Crofton KM, Setzer WR, Cooper RL, Stoker TE (2009) The effects of triclosan on puberty and thyroid hormones in male Wistar rats. Toxicol Sci 107:56–64. https://doi.org/10.1093/toxsci/kfn225
Acknowledgements
We sincerely thank all staff members in the hospital who contributed to this study and all participants for their great cooperation.
Funding
This research was supported by the National Natural Science Foundation of China (No. 81903272 and 42007287) and China Postdoctoral Science Foundation (No. 2018M643376).
Author information
Authors and Affiliations
Contributions
N-XW shared efforts in conducting data analysis, writing, and preparing the manuscript; L-JD shared efforts in conducting data analysis, writing, and preparing the manuscript; FX shared efforts in conducting data analysis, writing, and preparing the manuscript; J-YX shared efforts in conducting data analysis, writing, and preparing the manuscript. X-JL shared efforts in conducting data analysis, writing, and preparing the manuscript; QZ contributed to revise the manuscript. J-CS obtained data and revised the manuscript. DC contributed to revise the manuscript. PY supervised statistical analysis and revised the manuscript. All authors read and approved the final manuscript.
Corresponding author
Ethics declarations
Ethics approval and consent to participate
This study was approved by the Ethics Committee of Tongji Medical College, and each participant provided written informed consent.
Consent for publication
Not applicable.
Competing interests
The authors declare no competing interests.
Additional information
Responsible Editor: Lotfi Aleya
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
Wu, NX., Deng, LJ., Xiong, F. et al. Risk of thyroid cancer and benign nodules associated with exposure to parabens among Chinese adults in Wuhan, China. Environ Sci Pollut Res 29, 70125–70134 (2022). https://doi.org/10.1007/s11356-022-20741-w
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11356-022-20741-w