Skip to main content
SpringerLink
Log in

The Role of the Environment in Endocrine Cancers

  • Reference work entry
  • First Online:
Environmental Endocrinology and Endocrine Disruptors

Part of the book series: Endocrinology ((ENDOCR))

  • 282 Accesses

Abstract

Endocrine disrupting chemicals (EDCs) constitute exogenous agents which enter the body via food intake, inhalation, or direct contact. In addition to the lifelong exposure to environmental EDCs, a transplacental transfer seems to be also an important route. EDCs affect various aspects of the endocrine system leading to endocrine dysfunction. In addition, EDCs are involved in the pathogenesis of cancer in general, and endocrine cancer (EC) in particular. The association of EDCs with EC is mediated through their effects on immune balance, inflammation, and oxidative stress, all of them basic components in carcinogenesis. Besides, some EDCs present with a hormone-like activity acting on nuclear (genomic) and transmembrane receptors (nongenomic) leading to EC. The exact role of EDCs on EC development and/or its evolution is very complicated and has not been fully clarified, due to the complex and multifactorial pathogenesis of cancer and its lifelong manifestation. Although a quite large body of evidence support the role of EDCs in the pathogenesis of various endocrine disorders and some types of EC, there is limited evidence on their role in gonadal and adrenal cancer.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution

Institutional subscriptions

References

  • Ahmed KEM, et al. Effects of defined mixtures of POPs and endocrine disruptors on the steroid metabolome of the human H295R adrenocortical cell line. Chemosphere. 2019;218:328–39.

    Article  CAS  PubMed  Google Scholar 

  • Amant F, et al. Endometrial cancer. Lancet. 2005;366(9484):491–505.

    Article  PubMed  Google Scholar 

  • Behl M, et al. Comparative toxicity and carcinogenicity of soluble and insoluble cobalt compounds. Toxicology. 2015;333:195–205.

    Article  CAS  PubMed  Google Scholar 

  • Bidgoli SA, et al. Role of endocrine disrupting chemicals in the occurrence of benign uterine leiomyomata: special emphasis on AhR tissue levels. Asian Pac J Cancer Prev. 2012;13(11):5445–50.

    Article  PubMed  Google Scholar 

  • Bilgi A, et al. The apoptotic effects of bisphenol a exposure on the rat ovary: an experimental study. Environ Sci Pollut Res Int. 2019;26(10):10198–203.

    Article  CAS  PubMed  Google Scholar 

  • Bistakova J, et al. Effects of 4-nonylphenol on the steroidogenesis of human adrenocarcinoma cell line (NCI-H295R). J Environ Sci Health A Tox Hazard Subst Environ Eng. 2017;52(3):221–7.

    Article  CAS  PubMed  Google Scholar 

  • Bosl GJ, Motzer RJ. Testicular germ-cell cancer. N Engl J Med. 1997;337(4):242–53.

    Article  CAS  PubMed  Google Scholar 

  • Campion S, et al. Male reprotoxicity and endocrine disruption. Exp Suppl. 2012;101:315–60.

    PubMed  Google Scholar 

  • Chia VM, et al. International trends in the incidence of testicular cancer, 1973-2002. Cancer Epidemiol Biomark Prev. 2010a;19(5):1151–9.

    Article  Google Scholar 

  • Chia VM, et al. Effect modification of endocrine disruptors and testicular germ cell tumour risk by hormone-metabolizing genes. Int J Androl. 2010b;33(4):588–96.

    CAS  PubMed  Google Scholar 

  • Chou WC, et al. An integrative transcriptomic analysis reveals bisphenol a exposure-induced dysregulation of microRNA expression in human endometrial cells. Toxicol In Vitro. 2017;41:133–42.

    Article  CAS  PubMed  Google Scholar 

  • Dankers AC, et al. Endocrine disruptors differentially target ATP-binding cassette transporters in the blood-testis barrier and affect Leydig cell testosterone secretion in vitro. Toxicol Sci. 2013;136(2):382–91.

    Article  CAS  PubMed  Google Scholar 

  • de Angelis C, et al. The environment and male reproduction: the effect of cadmium exposure on reproductive function and its implication in fertility. Reprod Toxicol. 2017;73:105–27.

    Article  PubMed  Google Scholar 

  • De Martino MC, et al. The role of mTOR pathway as target for treatment in adrenocortical cancer. Endocr Connect. 2019;8(9):R144–56.

    Article  PubMed  PubMed Central  Google Scholar 

  • Del Pup L, et al. Endocrine disruptors and female cancer: informing the patients (review). Oncol Rep. 2015;34(1):3–11.

    Article  PubMed  Google Scholar 

  • Del Pup L, et al. Carcinogenetic mechanisms of endocrine disruptors in female cancers (review). Oncol Rep. 2016;36(2):603–12.

    Article  PubMed  PubMed Central  Google Scholar 

  • Diamanti-Kandarakis E, et al. Endocrine-disrupting chemicals: an Endocrine Society scientific statement. Endocr Rev. 2009;30(4):293–342.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Dogan S, Simsek T. Possible relationship between endocrine disrupting chemicals and hormone dependent gynecologic cancers. Med Hypotheses. 2016;92:84–7.

    Article  CAS  PubMed  Google Scholar 

  • Else T, et al. Adrenocortical carcinoma. Endocr Rev. 2014;35(2):282–326.

    Article  CAS  PubMed  Google Scholar 

  • Enangue Njembele AN, Bailey JL, Tremblay JJ. In vitro exposure of Leydig cells to an environmentally relevant mixture of organochlorines represses early steps of steroidogenesis. Biol Reprod. 2014;90(6):118.

    Article  PubMed  Google Scholar 

  • Gao H, et al. Bisphenol a and hormone-associated cancers: current progress and perspectives. Medicine (Baltimore). 2015;94(1):e211.

    Article  CAS  PubMed  Google Scholar 

  • Gibson DA, Saunders PT. Endocrine disruption of oestrogen action and female reproductive tract cancers. Endocr Relat Cancer. 2014;21(2):T13–31.

    Article  CAS  PubMed  Google Scholar 

  • Giudicessi JR, Ackerman MJ. Determinants of incomplete penetrance and variable expressivity in heritable cardiac arrhythmia syndromes. Transl Res. 2013;161(1):1–14.

    Article  PubMed  Google Scholar 

  • Gogola J, Hoffmann M, Ptak A. Persistent endocrine-disrupting chemicals found in human follicular fluid stimulate the proliferation of granulosa tumor spheroids via GPR30 and IGF1R but not via the classic estrogen receptors. Chemosphere. 2019;217:100–10.

    Article  CAS  PubMed  Google Scholar 

  • Greene MH, et al. Familial testicular germ cell tumors in adults: 2010 summary of genetic risk factors and clinical phenotype. Endocr Relat Cancer. 2010;17(2):R109–21.

    Article  PubMed  PubMed Central  Google Scholar 

  • Hall JM, Korach KS. Endocrine disrupting chemicals promote the growth of ovarian cancer cells via the ER-CXCL12-CXCR4 signaling axis. Mol Carcinog. 2013;52(9):715–25.

    Article  CAS  PubMed  Google Scholar 

  • Hanaoka T, et al. Urinary bisphenol a and plasma hormone concentrations in male workers exposed to bisphenol a diglycidyl ether and mixed organic solvents. Occup Environ Med. 2002;59(9):625–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Harada Y, et al. PPARalpha-dependent cholesterol/testosterone disruption in Leydig cells mediates 2,4-dichlorophenoxyacetic acid-induced testicular toxicity in mice. Arch Toxicol. 2016;90(12):3061–71.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hasle H, et al. Cancer incidence in men with Klinefelter syndrome. Br J Cancer. 1995;71(2):416–20.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hemminki K, et al. Obesity and familial obesity and risk of cancer. Eur J Cancer Prev. 2011;20(5):438–43.

    Article  PubMed  Google Scholar 

  • Horn-Ross PL, et al. Phytoestrogen intake and endometrial cancer risk. J Natl Cancer Inst. 2003;95(15):1158–64.

    Article  CAS  PubMed  Google Scholar 

  • Idrees MT, et al. The World Health Organization 2016 classification of testicular non-germ cell tumours: a review and update from the International Society of Urological Pathology Testis Consultation Panel. Histopathology. 2017;70(4):513–21.

    Article  PubMed  Google Scholar 

  • Kang NH, et al. Induced growth of BG-1 ovarian cancer cells by 17beta-estradiol or various endocrine disrupting chemicals was reversed by resveratrol via downregulation of cell cycle progression. Mol Med Rep. 2012;6(1):151–6.

    CAS  PubMed  Google Scholar 

  • Kang JS, Choi JS, Park JW. Transcriptional changes in steroidogenesis by perfluoroalkyl acids (PFOA and PFOS) regulate the synthesis of sex hormones in H295R cells. Chemosphere. 2016;155:436–43.

    Article  CAS  PubMed  Google Scholar 

  • Kim JY, et al. Methoxychlor and triclosan stimulates ovarian cancer growth by regulating cell cycle- and apoptosis-related genes via an estrogen receptor-dependent pathway. Environ Toxicol Pharmacol. 2014;37(3):1264–74.

    Article  CAS  PubMed  Google Scholar 

  • Lafferty JS, et al. Subchronic acrylamide treatment induces a tissue-specific increase in DNA synthesis in the rat. Toxicol Lett. 2004;154(1–2):95–103.

    Article  CAS  PubMed  Google Scholar 

  • Lauretta R, et al. Endocrine disrupting chemicals: effects on endocrine glands. Front Endocrinol (Lausanne). 2019;10:178.

    Article  PubMed  Google Scholar 

  • Liu J, et al. Fetal arsenic exposure appears to facilitate endocrine disruption by postnatal diethylstilbestrol in neonatal mouse adrenal. Chem Biol Interact. 2009;182(2–3):253–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Liu E, et al. Comparative toxicity and apoptosis induced by diorganotins in rat pheochromocytoma (PC12) cells. Food Chem Toxicol. 2013;60:302–8.

    Article  CAS  PubMed  Google Scholar 

  • Lymperi S, Giwercman A. Endocrine disruptors and testicular function. Metabolism. 2018;86:79–90.

    Article  CAS  PubMed  Google Scholar 

  • Ma XF, et al. IKKbeta/NF-kappaB mediated the low doses of bisphenol a induced migration of cervical cancer cells. Arch Biochem Biophys. 2015;573:52–8.

    Article  CAS  PubMed  Google Scholar 

  • Mallozzi M, et al. Endocrine disrupting chemicals and endometrial cancer: an overview of recent laboratory evidence and epidemiological studies. Int J Environ Res Public Health. 2017;14(3):334.

    Google Scholar 

  • Martinez-Arguelles DB, Papadopoulos V. Mechanisms mediating environmental chemical-induced endocrine disruption in the adrenal gland. Front Endocrinol (Lausanne). 2015;6:29.

    Article  PubMed  Google Scholar 

  • Mas A, et al. Developmental exposure to endocrine disruptors expands murine myometrial stem cell compartment as a prerequisite to leiomyoma tumorigenesis. Stem Cells. 2017;35(3):666–78.

    Article  CAS  PubMed  Google Scholar 

  • Mendiola J, et al. Are environmental levels of bisphenol associated with reproductive function in fertile men? Environ Health Perspect. 2010;118(9):1286–91.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Minner S, Schreiner J, Saeger W. Adrenal cancer: relevance of different grading systems and subtypes. Clin Transl Oncol. 2021;23(7):1350–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Nasiadek M, et al. The effect of cadmium on the coagulation and fibrinolytic system in women with uterine endometrial cancer and myoma. Int J Occup Med Environ Health. 2013;26(2):291–301.

    Article  PubMed  Google Scholar 

  • Ndossi DG, et al. An in vitro investigation of endocrine disrupting effects of trichothecenes deoxynivalenol (DON), T-2 and HT-2 toxins. Toxicol Lett. 2012;214(3):268–78.

    Article  CAS  PubMed  Google Scholar 

  • Nishi K, Hundal SS. Chlorpyrifos induced toxicity in reproductive organs of female Wistar rats. Food Chem Toxicol. 2013;62:732–8.

    Article  CAS  PubMed  Google Scholar 

  • Nori F, et al. Endocrine-disrupting chemicals and testicular cancer: a case-control study. Arch Environ Occup Health. 2006;61(2):87–95.

    Article  CAS  PubMed  Google Scholar 

  • Orr B, Edwards RP. Diagnosis and treatment of ovarian cancer. Hematol Oncol Clin North Am. 2018;32(6):943–64.

    Article  PubMed  Google Scholar 

  • Osbun N, et al. Characteristics of patients with Sertoli and Leydig cell testis neoplasms from a National Population-Based Registry. Clin Genitourin Cancer. 2017;15(2):e263–6.

    Article  PubMed  Google Scholar 

  • Pajewska M, et al. The determination of zearalenone and its major metabolites in endometrial cancer tissues. Anal Bioanal Chem. 2018;410(5):1571–82.

    Article  CAS  PubMed  Google Scholar 

  • Paoli D, et al. Exposure to polychlorinated biphenyls and hexachlorobenzene, semen quality and testicular cancer risk. J Endocrinol Investig. 2015;38(7):745–52.

    Article  CAS  Google Scholar 

  • Pivonello R, et al. The treatment of Cushing’s disease. Endocr Rev. 2015;36(4):385–486.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Rachon D. Endocrine disrupting chemicals (EDCs) and female cancer: informing the patients. Rev Endocr Metab Disord. 2015;16(4):359–64.

    Article  CAS  PubMed  Google Scholar 

  • Romkes M, Safe S. Comparative activities of 2,3,7,8-tetrachlorodibenzo-p-dioxin and progesterone as antiestrogens in the female rat uterus. Toxicol Appl Pharmacol. 1988;92(3):368–80.

    Article  CAS  PubMed  Google Scholar 

  • Rossing MA, et al. Risk of epithelial ovarian cancer in relation to benign ovarian conditions and ovarian surgery. Cancer Causes Control. 2008;19(10):1357–64.

    Article  PubMed  PubMed Central  Google Scholar 

  • Rutkowska AZ, et al. Endocrine disrupting chemicals as potential risk factor for estrogen-dependent cancers. Pol Arch Med Wewn. 2016;126(7–8):562–70.

    PubMed  Google Scholar 

  • Sanderson JT. The steroid hormone biosynthesis pathway as a target for endocrine-disrupting chemicals. Toxicol Sci. 2006;94(1):3–21.

    Article  CAS  PubMed  Google Scholar 

  • Scsukova S, Rollerova E, Bujnakova Mlynarcikova A. Impact of endocrine disrupting chemicals on onset and development of female reproductive disorders and hormone-related cancer. Reprod Biol. 2016;16(4):243–54.

    Article  PubMed  Google Scholar 

  • Shanmugalingam T, et al. Global incidence and outcome of testicular cancer. Clin Epidemiol. 2013;5:417–27.

    PubMed  PubMed Central  Google Scholar 

  • Shiraishi N, et al. Sensitivity to cadmium-induced genotoxicity in rat testicular cells is associated with minimal expression of the metallothionein gene. Toxicol Appl Pharmacol. 1995;130(2):229–36.

    Article  CAS  PubMed  Google Scholar 

  • Siegel RL, Miller KD, Jemal A. Cancer statistics, 2016. CA Cancer J Clin. 2016;66(1):7–30.

    Article  PubMed  Google Scholar 

  • Skakkebaek NE. A brief review of the link between environment and male reproductive health: lessons from studies of testicular germ cell cancer. Horm Res Paediatr. 2016;86(4):240–6.

    Article  CAS  PubMed  Google Scholar 

  • Skakkebaek NE, Rajpert-De Meyts E, Main KM. Testicular dysgenesis syndrome: an increasingly common developmental disorder with environmental aspects. Hum Reprod. 2001;16(5):972–8.

    Article  CAS  PubMed  Google Scholar 

  • Sung H, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2021;71(3):209–49.

    Article  PubMed  Google Scholar 

  • Takeuchi T, Tsutsumi O. Serum bisphenol a concentrations showed gender differences, possibly linked to androgen levels. Biochem Biophys Res Commun. 2002;291(1):76–8.

    Article  CAS  PubMed  Google Scholar 

  • Titus L, et al. Reproductive and hormone-related outcomes in women whose mothers were exposed in utero to diethylstilbestrol (DES): a report from the US National Cancer Institute DES third generation study. Reprod Toxicol. 2019;84:32–8.

    Article  CAS  PubMed  Google Scholar 

  • Trabert B, et al. International patterns and trends in testicular cancer incidence, overall and by histologic subtype, 1973–2007. Andrology. 2015;3(1):4–12.

    Article  CAS  PubMed  Google Scholar 

  • Tremoen NH, et al. Exposure to the three structurally different PCB congeners (PCB 118, 153, and 126) results in decreased protein expression and altered steroidogenesis in the human adrenocortical carcinoma cell line H295R. J Toxicol Environ Health A. 2014;77(9–11):516–34.

    Article  CAS  PubMed  Google Scholar 

  • Troisi R, et al. Prenatal diethylstilbestrol exposure and cancer risk in women. Environ Mol Mutagen. 2019;60(5):395–403.

    Article  CAS  PubMed  Google Scholar 

  • Tsikouras P, et al. Cervical cancer: screening, diagnosis and staging. J BUON. 2016;21(2):320–5.

    PubMed  Google Scholar 

  • Turnbull C, Rahman N. Genome-wide association studies provide new insights into the genetic basis of testicular germ-cell tumour. Int J Androl. 2011;34(4 Pt 2):86–96. discussion e96–7

    Article  Google Scholar 

  • Urriola-Munoz P, et al. Bisphenol-a and Nonylphenol induce apoptosis in reproductive tract cancer cell lines by the activation of ADAM17. Int J Mol Sci. 2018;19(8):2238.

    Google Scholar 

  • Waalkes MP, Rehm S, Devor DE. The effects of continuous testosterone exposure on spontaneous and cadmium-induced tumors in the male Fischer (F344/NCr) rat: loss of testicular response. Toxicol Appl Pharmacol. 1997;142(1):40–6.

    Article  CAS  PubMed  Google Scholar 

  • Winther CS, et al. Corticosteroid production in H295R cells during exposure to 3 endocrine disrupters analyzed with LC-MS/MS. Int J Toxicol. 2013;32(3):219–27.

    Article  PubMed  Google Scholar 

  • Yaguchi T. The endocrine disruptor bisphenol a promotes nuclear ERRgamma translocation, facilitating cell proliferation of grade I endometrial cancer cells via EGF-dependent and EGF-independent pathways. Mol Cell Biochem. 2019;452(1–2):41–50.

    Article  CAS  PubMed  Google Scholar 

  • Young HA, et al. Triazine herbicides and epithelial ovarian cancer risk in Central California. J Occup Environ Med. 2005;47(11):1148–56.

    Article  CAS  PubMed  Google Scholar 

  • Znaor A, et al. International variations and trends in testicular cancer incidence and mortality. Eur Urol. 2014;65(6):1095–106.

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Endocrine Unit, 2nd Propaedeutic Department of Internal Medicine, Research Institute and Diabetes Center, National and Kapodistrian University of Athens, Attikon University Hospital, Athens, Greece

    Melpomeni Peppa & Ioanna Mavroeidi

Authors
  1. Melpomeni Peppa
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ioanna Mavroeidi
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Dipartimento di Medicina Clinica e Chirurgia, Sezione di Endocrinologia, Unità di Andrologia e Medicina della Riproduzione e della Sessualità Maschile e Femminile (FERTISEXCARES), Università Federico II di Napoli, Naples, Italy

    Rosario Pivonello

  2. Medical School, National and Kapodistrian University of Athens, Athens, Greece

    Evanthia Diamanti-Kandarakis

Rights and permissions

Reprints and permissions

Copyright information

© 2023 Springer Nature Switzerland AG

About this entry

Check for updates. Verify currency and authenticity via CrossMark

Cite this entry

Peppa, M., Mavroeidi, I. (2023). The Role of the Environment in Endocrine Cancers. In: Pivonello, R., Diamanti-Kandarakis, E. (eds) Environmental Endocrinology and Endocrine Disruptors . Endocrinology. Springer, Cham. https://doi.org/10.1007/978-3-030-39044-0_16

Download citation

  • DOI: https://doi.org/10.1007/978-3-030-39044-0_16

  • Published:

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-030-39043-3

  • Online ISBN: 978-3-030-39044-0

  • eBook Packages: MedicineReference Module Medicine

Publish with us

Policies and ethics

Search

Navigation