Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.
ADVANCED SEARCH
Log in
Top
BMC Cancer
Published in: BMC Cancer 1/2018

Open Access 01-12-2018 | Research article

A case-control study of exposure to organophosphate flame retardants and risk of thyroid cancer in women

Authors: Nicole C. Deziel, Huangdi Yi, Heather M. Stapleton, Huang Huang, Nan Zhao, Yawei Zhang

Published in: BMC Cancer | Issue 1/2018

Login to get access

Abstract

Background

Growing evidence demonstrates that exposure to organophosphate flame retardants (PFRs) is widespread and that these chemicals can alter thyroid hormone regulation and function. We investigated the relationship between PFR exposure and thyroid cancer and whether individual or temporal factors predict PFR exposure.

Methods

We analyzed interview data and spot urine samples collected in 2010–2013 from 100 incident female, papillary thyroid cancer cases and 100 female controls of a Connecticut-based thyroid cancer case-control study. We measured urinary concentrations of six PFR metabolites with mass spectrometry. We estimated odds ratios (OR) and 95% confidence intervals (95% CI) for continuous and categories (low, medium, high) of concentrations of individual and summed metabolites, adjusting for potential confounders. We examined relationships between concentrations of PFR metabolites and individual characteristics (age, smoking status, alcohol consumption, body mass index [BMI], income, education) and temporal factors (season, year) using multiple linear regression analysis.

Results

No PFRs were significantly associated with papillary thyroid cancer risk. Results remained null when stratified by microcarcinomas (tumor diameter ≤ 1 cm) and larger tumor sizes (> 1 cm). We observed higher urinary PFR concentrations with increasing BMI and in the summer season.

Conclusions

Urinary PFR concentrations, measured at time of diagnosis, are not linked to increased risk of thyroid cancer. Investigations in a larger population or with repeated pre-diagnosis urinary biomarker measurements would provide additional insights into the relationship between PFR exposure and thyroid cancer risk.
Appendix
Available only for authorised users
Literature
1.
Howlader N, Noone AM, Krapcho M, Miller D, Bishop K, Kosary CL, Yu M, Ruhl J, Tatalovich Z, Mariotto A, Lewis DR, Chen HS, Feuer EJ, Cronin KA (eds). SEER Cancer Statistics Review, 1975–2014; National Cancer Institute. Bethesda, MD, https://​seer.​cancer.​gov/​csr/​1975_​2014/​, based on November 2016 SEER data submission, posted to the SEER web site, April 2017.
2.
3.
Lubitz CC, Kong CY, McMahon PM, Daniels GH, Chen Y, Economopoulos KP, Gazelle GS, Weinstein MC. Annual financial impact of well-differentiated thyroid cancer care in the United States. Cancer. 2014;120(9):1345–52.CrossRefPubMedPubMedCentral
4.
Brown AP, Chen J, Hitchcock YJ, Szabo A, Shrieve DC, Tward JD. The risk of second primary malignancies up to three decades after the treatment of differentiated thyroid cancer. J Clin Endocrinol Metab. 2008;93(2):504–15.CrossRefPubMed
5.
Kim C, Bi X, Pan D, Chen Y, Carling T, Ma S, Udelsman R, Zhang Y. The risk of second cancers after diagnosis of primary thyroid cancer is elevated in thyroid microcarcinomas. Thyroid. 2013;23(5):575–82.CrossRefPubMedPubMedCentral
6.
Husson O, Haak HR, Buffart LM, Nieuwlaat WA, Oranje WA, Mols F, Kuijpens JL, Coebergh JW. Van de poll-Franse LV. Health-related quality of life and disease specific symptoms in long-term thyroid cancer survivors: a study from the population-based PROFILES registry. Acta Oncol. 2013;52(2):249–58.CrossRefPubMed
7.
Imaizumi M, Ohishi W, Nakashima E, Nobuko S, Neriishi K, Yamada M, et al. Association of radiation dose with prevalence of thyroid nodules among atomic bomb survivors exposed in childhood (2007-2011). JAMA Intern Med. 2015;175(2):228–36.CrossRefPubMed
8.
Ron E, Lubin JH, Shore RE, Mabuchi K, Modan B, Pottern LM, Schneider AB, Tucker MA, Boice JD Jr. Thyroid cancer after exposure to external radiation: a pooled analysis of seven studies. Radiat Res. 1995;141(3):259–77.CrossRefPubMed
9.
10.
Kitahara CM, McCullough ML, Franceschi S, Rinaldi S, Wolk A, Neta G, et al. Anthropometric factors and thyroid Cancer risk by histological subtype: pooled analysis of 22 prospective studies. Thyroid. 2016;26(2):306–18.CrossRefPubMedPubMedCentral
11.
Rinaldi S, Lise M, Clavel-Chapelon F, Boutron-Ruault MC, Guillas G, Overvad K, et al. Body size and risk of differentiated thyroid carcinomas: findings from the EPIC study. Int J Cancer. 2012;131(6):E1004–14.CrossRefPubMed
12.
Davies L, Welch HG. Current thyroid Cancer trends in the United States. JAMA Otolaryngol Head Neck Surg. 2014;140(4):317–22.CrossRefPubMed
13.
Davies L, Welch HG. Increasing incidence of thyroid cancer in the United States, 1973-2002. JAMA. 2006;295(18):2164–7.CrossRefPubMed
14.
Ward EM, Jemal A, Chen A. Increasing incidence of thyroid cancer: is diagnostic scrutiny the sole explanation? Future Oncol. 2010;6(2):185–8.CrossRefPubMed
15.
Chen AY, Jemal A, Ward EM. Increasing incidence of differentiated thyroid cancer in the United States, 1988-2005. Cancer. 2009;115(16):3801–7.CrossRefPubMed
16.
Zhu C, Zheng T, Kilfoy BA, Han X, Ma S, Ba Y, Bai Y, Wang R, Zhu Y, Zhang Y. A birth cohort analysis of the incidence of papillary thyroid cancer in the United States, 1973-2004. Thyroid. 2009;19(10):1061–6.CrossRefPubMedPubMedCentral
17.
Cho YY, Jang HW, Joung JY, Park SM, Jeong DJ, Kim SW, et al. Trends in thyroid Cancer incidence in Korean children (1999-2012) based on palpation and nonpalpation detection methods. Eur Thyroid J. 2015;4(4):252–9.CrossRefPubMedPubMedCentral
18.
Vergamini LB, Frazier AL, Abrantes FL, Ribeiro KB, Rodriguez-Galindo C. Increase in the incidence of differentiated thyroid carcinoma in children, adolescents, and young adults: a population-based study. J Pediatr. 2014;164(6):1481–5.CrossRefPubMed
19.
Aschebrook-Kilfoy B, Grogan RH, Ward MH, Kaplan E, Devesa SS. Follicular thyroid cancer incidence patterns in the United States, 1980-2009. Thyroid. 2013;23(8):1015–21.CrossRefPubMedPubMedCentral
20.
21.
Aschebrook-Kilfoy B, Ward MH, Sabra MM, Devesa SS. Thyroid cancer incidence patterns in the United States by histologic type, 1992-2006. Thyroid. 2011;21(2):125–34.CrossRefPubMedPubMedCentral
22.
Enewold L, Zhu K, Ron E, Marrogi AJ, Stojadinovic A, Peoples GE, Devesa SS. Rising thyroid cancer incidence in the United States by demographic and tumor characteristics, 1980-2005. Cancer Epidemiol Biomark Prev. 2009;18(3):784–91.CrossRef
23.
Ba Y, Huang H, Lerro CC, Li S, Zhao N, Li A, Ma S, Udelsman R, Zhang Y. Occupation and thyroid Cancer: a population-based, case-control study in Connecticut. J Occup Environ Med. 2016;58(3):299–305.CrossRefPubMedPubMedCentral
24.
Hoffman K, Sosa JA, Stapleton HM. Do flame retardant chemicals increase the risk for thyroid dysregulation and cancer? Curr Opin Oncol. 2017;29(1):7–13.CrossRefPubMed
25.
Dishaw LV, L JM, Roberts SC, Stapleton HM. Exposures, mechanisms, and impacts of endocrine-active flame retardants. Curr Opin Pharmacol. 2014;19c:125–33.CrossRef
26.
Stapleton HM, Sharma S, Getzinger G, Ferguson PL, Gabriel M, Webster TF, Blum A. Novel and high volume use flame retardants in US couches reflective of the 2005 PentaBDE phase out. Environ Sci Technol. 2012;46(24):13432–9.CrossRefPubMedPubMedCentral
27.
Greaves AK, Letcher RJ. A review of organophosphate esters in the environment from biological effects to distribution and fate. Bull Environ Contam Toxicol. 2017;98(1):2–7.CrossRefPubMed
28.
Stapleton HM, Allen JG, Kelly SM, Konstantinov A, Klosterhaus S, Watkins D, et al. Alternate and new brominated flame retardants detected in U.S. house dust. Environ Sci Technol. 2008;42(18):6910–6.CrossRefPubMed
29.
Stapleton HM, Klosterhaus S, Eagle S, Fuh J, Meeker JD, Blum A, Webster TF. Detection of organophosphate flame retardants in furniture foam and U.S. house dust. Environ Sci Technol. 2009;43(19):7490–5.CrossRefPubMedPubMedCentral
30.
California Environmental Protection Agency Department of Toxic Substances Control. Priority Product Profile: Children’s Foam-Padded Sleeping Products Containing TDCPP. 2014.
31.
Mendelsohn E, Hagopian A, Hoffman K, Butt CM, Lorenzo A, Congleton J, Webster TF, Stapleton HM. Nail polish as a source of exposure to triphenyl phosphate. Environ Int. 2016;86:45–51.CrossRefPubMed
32.
Ballesteros-Gomez A, Brandsma SH, de Boer J, Leonards PE. Analysis of two alternative organophosphorus flame retardants in electronic and plastic consumer products: resorcinol bis-(diphenylphosphate) (PBDPP) and bisphenol a bis (diphenylphosphate) (BPA-BDPP). Chemosphere. 2014;116:10–4.CrossRefPubMed
33.
van der Veen I, de Boer J. Phosphorus flame retardants: properties, production, environmental occurrence, toxicity and analysis. Chemosphere. 2012;88(10):1119–53.CrossRefPubMed
34.
Butt CM, Congleton J, Hoffman K, Fang M, Stapleton HM. Metabolites of organophosphate flame retardants and 2-ethylhexyl tetrabromobenzoate in urine from paired mothers and toddlers. Environ Sci Technol. 2014;48(17):10432–8.CrossRefPubMed
35.
Hoffman K, Lorenzo A, Butt CM, Adair L, Herring AH, Stapleton HM, Daniels JL. Predictors of urinary flame retardant concentration among pregnant women. Environ Int. 2017;98:96–101.CrossRefPubMed
36.
Meeker JD, Cooper EM, Stapleton HM, Hauser R. Urinary metabolites of organophosphate flame retardants: temporal variability and correlations with house dust concentrations. Environ Health Perspect. 2013;121(5):580–5.CrossRefPubMedPubMedCentral
37.
Butt CM, Hoffman K, Chen A, Lorenzo A, Congleton J, Stapleton HM. Regional comparison of organophosphate flame retardant (PFR) urinary metabolites and tetrabromobenzoic acid (TBBA) in mother-toddler pairs from California and New Jersey. Environ Int. 2016;94:627–34.CrossRefPubMedPubMedCentral
38.
Castorina R, Butt C, Stapleton HM, Avery D, Harley KG, Holland N, Eskenazi B, Bradman A. Flame retardants and their metabolites in the homes and urine of pregnant women residing in California (the CHAMACOS cohort). Chemosphere. 2017;179:159–66.CrossRefPubMedPubMedCentral
39.
Kosarac I, Kubwabo C, Foster WG. Quantitative determination of nine urinary metabolites of organophosphate flame retardants using solid phase extraction and ultra performance liquid chromatography coupled to tandem mass spectrometry (UPLC-MS/MS). J Chromatogr B. 2016;1014:24–30.CrossRef
40.
Feng L, Ouyang F, Liu L, Wang X, Wang X, Li YJ, et al. Levels of urinary metabolites of organophosphate flame retardants, TDCIPP, and TPHP, in pregnant women in shanghai. J Environ Public Health. 2016;2016:9416054.CrossRefPubMedPubMedCentral
41.
Farhat A, Crump D, Chiu S, Williams KL, Letcher RJ, Gauthier LT, Kennedy SW. In Ovo effects of two organophosphate flame retardants--TCPP and TDCPP--on pipping success, development, mRNA expression, and thyroid hormone levels in chicken embryos. Toxicol Sci. 2013;134(1):92–102.CrossRefPubMed
42.
Liu X, Ji K, Choi K. Endocrine disruption potentials of organophosphate flame retardants and related mechanisms in H295R and MVLN cell lines and in zebrafish. Aquat Toxicol. 2012;114-115:173–81.CrossRefPubMed
43.
Liu X, Ji K, Jo A, Moon HB, Choi K. Effects of TDCPP or TPP on gene transcriptions and hormones of HPG axis, and their consequences on reproduction in adult zebrafish (Danio rerio). Aquat Toxicol. 2013;134-135:104–11.CrossRefPubMed
44.
Wang Q, Lai NL, Wang X, Guo Y, Lam PK, Lam JC, Zhou B. Bioconcentration and transfer of the organophorous flame retardant 1,3-dichloro-2-propyl phosphate causes thyroid endocrine disruption and developmental neurotoxicity in zebrafish larvae. Environ Sci Technol. 2015;49(8):5123–32.CrossRefPubMed
45.
Xu T, Wang Q, Shi Q, Fang Q, Guo Y, Zhou B. Bioconcentration, metabolism and alterations of thyroid hormones of Tris(1,3-dichloro-2-propyl) phosphate (TDCPP) in zebrafish. Environ Toxicol Pharmacol. 2015;40(2):581–6.CrossRefPubMed
46.
Kim S, Jung J, Lee I, Jung D, Youn H, Choi K. Thyroid disruption by triphenyl phosphate, an organophosphate flame retardant, in zebrafish (Danio rerio) embryos/larvae, and in GH3 and FRTL-5 cell lines. Aquat Toxicol. 2015;160c:188–96.CrossRef
47.
Liu X, Jung D, Jo A, Ji K, Moon HB, Choi K. Long-term exposure to triphenylphosphate alters hormone balance and HPG, HPI, and HPT gene expression in zebrafish (Danio rerio). Environ Toxicol Chem. 2016;35(9):2288–96.CrossRefPubMed
48.
Hill KL, Hamers T, Kamstra JH, Willmore WG, Letcher RJ. Organophosphate triesters and selected metabolites enhance binding of thyroxine to human transthyretin in vitro. Toxicol Lett. 2018;285:87–93.CrossRefPubMed
49.
Meeker JD. Exposure to environmental endocrine disrupting compounds and men's health. Maturitas. 2010;66(3):236–41.CrossRefPubMed
50.
Meeker JD, Cooper EM, Stapleton HM, Hauser R. Exploratory analysis of urinary metabolites of phosphorus-containing flame retardants in relation to markers of male reproductive health. Endocrine Disruptors. 2013;1(1):e26306.CrossRefPubMedPubMedCentral
51.
Preston EV, McClean MD, Claus Henn B, Stapleton HM, Braverman LE, Pearce EN, Makey CM, Webster TF. Associations between urinary diphenyl phosphate and thyroid function. Environ Int. 2017;101:158–64.CrossRefPubMedPubMedCentral
52.
Moeller LC, Fuhrer D. Thyroid hormone, thyroid hormone receptors, and cancer: a clinical perspective. Endocr Relat Cancer. 2013;20(2):R19–29.CrossRefPubMed
53.
Huang H, Rusiecki J, Udelsman R, Zhang Y. TSH, thyroid hormone, and PTC-response. Cancer Epidemiol Biomark Prev. 2018;27(2):228–9.CrossRef
54.
Huang H, Rusiecki J, Zhao N, Chen Y, Ma S, Yu H, Ward MH, Udelsman R, Zhang Y. Thyroid-stimulating hormone, thyroid hormones, and risk of papillary thyroid Cancer: a nested case-control study. Cancer Epidemiol Biomark Prev. 2017;26(8):1209–18.CrossRef
55.
Franco AT, Malaguarnera R, Refetoff S, Liao XH, Lundsmith E, Kimura S, et al. Thyrotrophin receptor signaling dependence of Braf-induced thyroid tumor initiation in mice. Proc Natl Acad Sci U S A. 2011;108(4):1615–20.CrossRefPubMedPubMedCentral
56.
Zhang Y, Chen Y, Huang H, Sandler J, Dai M, Ma S, Udelsman R. Diagnostic radiography exposure increases the risk for thyroid microcarcinoma: a population-based case-control study. Eur J Cancer Prev. 2015;24(5):439–46.CrossRefPubMedPubMedCentral
57.
58.
Hoffman K, Butt CM, Webster TF, Preston EV, Hammel SC, Makey C, et al. Temporal trends in exposure to organophosphate flame retardants in the United States. Environ Sci Technol Lett. 2017;4(3):112–8.CrossRefPubMedPubMedCentral
59.
Tung EWY, Peshdary V, Gagne R, Rowan-Carroll A, Yauk CL, Boudreau A, et al. Adipogenic effects and gene expression profiling of Firemaster(R) 550 components in human primary Preadipocytes. Environ Health Perspect. 2017;125(9):097013.CrossRefPubMedPubMedCentral
60.
Xu F, Giovanoulis G, van Waes S, Padilla-Sanchez JA, Papadopoulou E, Magner J, et al. Comprehensive study of human external exposure to organophosphate flame retardants via air, dust, and hand wipes: the importance of sampling and assessment strategy. Environ Sci Technol. 2016;50(14):7752–60.CrossRefPubMed
61.
Hoffman K, Daniels JL, Stapleton HM. Urinary metabolites of organophosphate flame retardants and their variability in pregnant women. Environ Int. 2014;63:169–72.CrossRefPubMed
Metadata
Title
A case-control study of exposure to organophosphate flame retardants and risk of thyroid cancer in women
Authors
Nicole C. Deziel
Huangdi Yi
Heather M. Stapleton
Huang Huang
Nan Zhao
Yawei Zhang
Publication date
01-12-2018
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2018
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/s12885-018-4553-9

Other articles of this Issue 1/2018

BMC Cancer 1/2018 Go to the issue

Research article

A computational study of hedgehog signalling involved in basal cell carcinoma reveals the potential and limitation of combination therapy

Study protocol

Phase I clinical study of brentuximab vedotin (SGN-35) involving children with recurrent or refractory CD30-positive Hodgkin’s lymphoma or systemic anaplastic large cell lymphoma: rationale, design and methods of BV-HLALCL study: study protocol

Research article

Prognostic value of serum CYFRA 21-1 1 in patients with anal canal squamous cell carcinoma treated with radio(chemo)therapy

Research article

Application of Ventana immunocytochemical analysis on ThinPrep cytology slides for detection of ALK rearrangement in patients with advanced non–small-cell lung cancer

Research article

Pancreatic ductal adenocarcinoma can be detected by analysis of volatile organic compounds (VOCs) in alveolar air

Research article

Frequency of HPV in oral cavity squamous cell carcinoma
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine
Image Credits