Endocrine Disrupting Chemicals and their Role in Cancer-A review
ODANGOWEI INETIMINEBI OGIDI*1, AKPOFINIERE MONICA TAWARIOWEI2
1Department of Biochemistry,
Bayelsa Medical University
Yenagoa, Bayelsa State,
NIGERIA
2Department of Science Laboratory Technology,
Federal Polytechnic, Ekowe,
Bayelsa State,
NIGERIA
Abstract: - Endocrine-disrupting chemicals (EDCs), which are environmentally prevalent compounds, have the
ability to interact with the body's endocrine system and thus exert detrimental effects on human health. Despite
persistent concerns over public health, endocrine-disrupting chemicals (EDCs) remain integral components of
commonplace consumer products, rendering them ubiquitous pollutants for individuals. In light of the
numerous epidemiological and experimental studies that have established a connection between endocrine-
disrupting chemicals and adverse effects on human health, there has been an increased emphasis on mitigating
human exposure to these compounds. There exists a correlation between endocrine-disrupting drugs and
adverse impacts on human health, as well as an elevated susceptibility to hormone-sensitive cancers such as
breast, uterine, ovarian, prostate, and thyroid cancers. The objective of this study was to provide a
comprehensive overview of previous studies investigating the relationship between endocrine-disrupting
chemicals and the development of cancer.
Key-Words: - Endocrine disruptive substances, Hormones, Breast, Uterus, Ovaries, Prostate, Thyroid
Received: May 28, 2022. Revised: August 8, 2023. Accepted: September 11, 2023. Published: October 5, 2023.
1 Introduction
Endocrine disruptors were defined as "an exogenous
substance or mixture that alters adverse health
effects in an intact organism, its progeny, or (sub)
populations by the World Health Organisation in
2002. For decades, it has been known that both
natural and synthetic substances can imitate the
actions of hormones in humans and other
vertebrates [1]. Endocrine disruptive substances are
widely present in the environment, which causes
them to enter the food chain and be consumed by
people. Various routes of exposure can lead
individuals to encounter chemicals that alter
hormone function, such as the act of ingesting food
that has been intentionally contaminated by
additives or packaging materials during the process
of food preparation, with the aim of safeguarding
the quality and safety of food products; the
consumption of dirty water; the inhalation of
contaminated air; and the contact of the skin with
contaminated cosmetics, personal care items, or soil.
Food is regarded as the main way that
endocrine-disrupting chemicals are exposed because
it is necessary for living. It is irrelevant that dietary
choices may influence how much exposure people
receive to endocrine-disrupting substances. For
instance, those who consume more conventional
food than organic food in their diets will be exposed
to more pesticides even when living in the same
geographic area [2]. For the same reason, people
who eat more oily fish, meat, and dairy products
would be exposed to more persistent endocrine
disruptors like dichlorodiphenyltrichloroethane
İD
İD
MOLECULAR SCIENCES AND APPLICATIONS
DOI: 10.37394/232023.2023.3.2
Odangowei Inetiminebi Ogidi,
Akpofiniere Monica Tawariowei
E-ISSN: 2732-9992
5
Volume 3, 2023
(DDT) than people who eat more vegetables [3].
This is because the lipid fraction of these foods is
where the lipophilic persistent endocrine disrupting
chemicals bioaccumulate.
However, it has long been believed that
prenatal environmental exposure, which occurs
during a period of rapid human development, has a
significant role in the development of malignancies
in children and young people. There is clear
evidence of two environmental agents, ionising
radiation and the oestrogen against diethylstilbestrol
(DES), even though a large spectrum of potentially
hazardous chemicals may be at play [4]. Endocrine
disruptors, in general, are chemical substances,
primarily obtained from industrial manufacture that
can obstruct the endocrine system's regular
operation [5].
Polybrominated diphenyl ethers (PBDEs),
organophosphorus pesticides (OPs), phthalates,
bisphenol A (BPA), and their analogues, as well as
"older" persistent organic pollutants (POPs) like
dichlorodiphenyltrichloroethane (DDT), chlorinated
dioxins, and polychlorinated biphenyls (PCBs), are
all well-known examples. Frequent exposure to any
of these substances remains possible. According to
multiple studies, these substances have been
identified in various bodily components such as
body fat, breast milk, blood, and urine.
Nevertheless, previous studies have shown that the
implementation of corrective measures by either the
government or manufacturers has led to a decrease
in the accumulation of particular chemicals in the
human body, such as dioxin-like compounds [6].
The majority of these compounds are
extensively used in industry, agriculture, and several
consumer goods. Their interactions with endocrine
receptors like oestrogen receptors (ERs) or changes
to their signalling pathways are primarily
responsible for their effects, which can interfere
with the normal growth and function of some organs
[7]. This review will focus on endocrine-disrupting
chemicals and how they affect cancer.
2 Endocrine Disrupting Chemicals
According to the Endocrine Society, endocrine-
disrupting chemicals (EDCs) are defined as
exogenous (non-natural) substances or combinations
of substances that disrupt the normal functioning of
hormones. These substances have the ability to
imitate hormones, hinder the production or
breakdown of hormones, influence the development
of hormone receptors, function as hormone
antagonists, or modify hormone binding through
various processes. Several instances of artificially
produced commodities that commonly emit
environmental endocrine-disrupting chemicals
(EDCs) throughout their production and utilisation
include pesticides, plastics and plasticizers, metals,
electronic trash, flame retardants, food additives,
and personal care items. Endocrine-disrupting
chemicals (EDCs) possess the capacity to perturb
the equilibrium of hormones, thereby giving rise to
a range of health complications. These
complications encompass alterations in the immune
system, atypical growth patterns in children,
anomalies in development and reproduction, an
elevated incidence of hormone-sensitive cancers,
and further developmental and reproductive
abnormalities [9].
Endocrine-disrupting chemicals (EDCs) are
a broad category of artificially synthesised
substances that exhibit remarkable diversity and find
application in various contexts. Common substances
in this group include pesticides like methoxychlor,
chlorpyrifos, and dichlorodiphenyltrichloroethane
(DDT), as well as industrial chemicals and their
byproducts like polychlorinated biphenyls (PCBs),
polybrominated biphenyls (PBBs), and dioxins.
Endocrine-disrupting chemicals (EDCs) with long
half-lives were first made for use in industry. They
were called "persistent organic pollutants" (POPs) at
the time. This category encompasses several
substances such as polychlorinated biphenyls
(PCBs), dichlorodiphenyldichloroethylene (DDE),
dioxin, organochlorine insecticides, and
hexachlorobenzene (HCB). As a result of their
pronounced lipophilic properties, persistent organic
pollutants (POPs) exhibit a propensity for
bioaccumulation within adipose tissue. This
characteristic leads to their accumulation in the food
chain and subsequent biomagnification [10].
Some substances have the potential to undergo
metabolic processes that result in the formation of
molecules that are more hazardous than the original
chemicals. In contrast, a significant number of these
substances either do not degrade or degrade at a
sluggish rate. Although lacking in persistence, other
endocrine-disrupting chemicals (EDCs) such as
bisphenol A (BPA) and phthalates are extensively
utilised, resulting in widespread exposure among
individuals in the environment. Individuals are
consistently subjected to endocrine-disrupting
chemicals (EDCs) via several routes, including
MOLECULAR SCIENCES AND APPLICATIONS
DOI: 10.37394/232023.2023.3.2
Odangowei Inetiminebi Ogidi,
Akpofiniere Monica Tawariowei
E-ISSN: 2732-9992
6
Volume 3, 2023
inhalation, dermal exposure, consumption of food
and water, and respiration.
Endocrine-disrupting chemicals (EDCs) can
affect many hormone systems, but research has
shown that their main effects are seen in the
reproductive system of developing foetuses, the start
of puberty, embryonic development, and the process
of sex differentiation. The primary mechanism of
action of endocrine-disrupting chemicals (EDCs) is
believed to be the disruption of sex steroid
hormones. There is an increasing level of worry
over the potential association between EDCs and
metabolic illnesses in adults.
2.1 Sources of EDCs Exposure
Endocrine-disrupting chemicals (EDCs) encompass
a range of compounds, both naturally occurring and
synthetic, that possess the capacity to imitate
hormonal responses through their interference with
or modification of the many systems within the
endocrine system [11–13]. Bisphenols, including
bisphenol A (BPA), and phthalates are crucial
chemical compounds employed as primary
constituents in the plastics manufacturing sector
[14]. Additional categories of endocrine-disrupting
chemicals (EDCs) encompass phytoestrogens,
polybrominated diphenyl ethers (PBDE),
polychlorinated biphenyls (PCB), dioxins,
perchlorate, perfluoroalkyl, and polyfluoroalkyl
compounds, polychlorinated biphenyls (PCB), and
triclosan, which are frequently ingested by
individuals [15, 16].
According to a comprehensive review of the
literature, a significant proportion of endocrine-
disrupting chemicals (EDCs) are extensively utilised
and frequently encountered on a global scale.
Manufacturing processes result in the production of
thermal receipts, epoxy resins, dental sealants, food
packaging, and BPA derivatives (specifically
bisphenol S, F, and E) [17-19]. High-molecular-
weight phthalates, such as di (2-ethylhexyl)
phthalate (DEHP), di-isononyl phthalate, di-isodecyl
phthalate, and benzylbutyl phthalate, play a crucial
role in the manufacturing of various products,
including polyvinyl chloride (PVC) plastics,
medical devices, pharmaceutical coatings, food
packaging, car interiors, drinking straws, and
adhesives [20].
Phthalates with low molecular weight,
including di-n-butyl phthalate, di-iso-butyl
phthalate, and di-ethyl phthalate, can be found in
many products such as pesticides, nail polish,
deodorants, and perfumes [20]. The two most
prevalent endocrine-disrupting chemicals (EDCs),
namely bisphenol A (BPA) and phthalates, are
utilised in the production of furniture foam,
fireworks, liquid body wash, and hydraulic fluids,
respectively. These EDCs have the potential to be
consumed through the ingestion of food and
beverages that have been packaged in containers
containing these chemicals [21]. In addition, these
items are also found to contain triclosan,
perchlorate, polychlorinated biphenyls (PCBs), and
polybrominated diphenyl ethers (PBDEs). Because
endocrine-disrupting chemicals (EDCs) are easy to
find, people can get in touch with them in many
different ways, such as through transdermal
absorption, oral ingestion, inhalation, and injection
[22, 23].
3 Cancer
Cancer ranks as the second-leading cause of
mortality on a global scale. In the year 2014, the
United States had a total of 1,665,540 reported
occurrences of the aforementioned sickness,
resulting in the unfortunate demise of 585,720
people. In recent years, there has been a notable
increase in the prevalence of cancer among
individuals. As a consequence of these factors,
cancer emerges as a significant health concern that
impacts various human populations. In the year
2018, a total of 9.6 million deaths were attributed to
cancer, and 18.1 million new cases of cancer were
documented across 185 nations [24]. The genesis of
cancer is attributed to a sequence of genetic
modifications that impact cellular functionality. The
involvement of chemicals in the development of
malignant cells and genetic alterations is evident.
The association between endocrine-
disrupting chemicals (EDCs) and cancer has been
established for over a decade. The carcinogenic
qualities of some endocrine-disrupting chemicals
(EDCs) have been scientifically demonstrated,
leading to the acceleration of cancer progression and
metastasis [25–27]. The role of microRNAs, which
are recognised as regulators of gene expression
through negative regulatory mechanisms, has lately
been implicated in the pathogenesis of cancer [28].
Onco-miR-21, which estrogen controls, and the
development of breast cancer are related, according
MOLECULAR SCIENCES AND APPLICATIONS
DOI: 10.37394/232023.2023.3.2
Odangowei Inetiminebi Ogidi,
Akpofiniere Monica Tawariowei
E-ISSN: 2732-9992
7
Volume 3, 2023
to research [29]. Dioxins, DEHP, and BPA have the
ability to activate oestrogen receptors, facilitating
the proliferation of hormone-dependent
malignancies such as breast and prostate tumours
[30].
EDCs have the capability to bind to a
limited number of nuclear receptors, such as the
ooestrogen receptors (ER and GPR30), the androgen
receptor (AR), the thyroid hormone receptors (TR
and ERR), the estrogen-related receptor gamma
(ERR), and the glucocorticoid receptor (GR). The
interaction between endocrine-disrupting chemicals
(EDCs) and estrogen receptors (ER) promotes the
growth and movement of several cancer cell
populations through the activation of Stat3 and
ERK1/2 signalling pathways [25–30].
A study was conducted to investigate the
association between endocrine disruptors and the
risk of thyroid cancer in a sample of 960
individuals, consisting of 462 thyroid cancer
patients and 498 control subjects. The findings
revealed that individuals exposed to endocrine
disruptors had a significantly elevated risk of
developing thyroid cancer compared to those in the
control group [31]. Based on a study of 264 women
from mammography clinics, it was found that
circulating serum levels of endocrine-disrupting
chemicals (EDCs) are positively related to
mammographic breast density, which is known to be
a risk factor for breast cancer [32]. In particular, the
research showed a link between the levels of
bisphenol A (BPA) and mono-ethyl phthalate in the
blood and mammographic breast density. The study
demonstrated a significant elevation in the risk of
prostate cancer due to exposure to dioxins, arsenic,
and PCBs. Similarly, an elevated risk of breast
cancer was shown in relation to exposure to PCBs
and phytoestrogens [33].
3.1 Roles of Endocrine Disrupting Chemicals
in Prostrate Cancer
Endocrine-disrupting chemicals (EDCs) have been
identified as compounds that have the potential to
increase the likelihood of developing endocrine-
related disorders, such as prostate cancer (PCa).
This association is based on the "Endocrine
Disrupting Chemicals Hypothesis" put forth during
the Wingspread conference in 1991 [34, 35].
Prostate cancer is the prevailing form of cancer and
ranks as the second leading cause of death among
Caucasian males [16, 36]. In the past, risk
assessments have typically been carried out on a
chemical-by-chemical basis. However, regulatory
bodies are now recognising the importance of
considering the collective impact of multiple
chemicals. The widely acknowledged notion is that
humans are consistently exposed to various
pollutants [37, 38]. In order to underscore the
simultaneous impact of various chemicals on
prostate diseases, it is imperative, according to this
viewpoint, to investigate the outcomes of collective
exposure to several prostate diseases rather than
isolated substances [39].
Exposure to a diverse range of endocrine-
disrupting drugs has the ability to disrupt the typical
equilibrium of androgen and estrogen levels in both
humans and animals. This disruption can lead to the
development of sex hormone-related diseases or
ailments [40]. Lim et al. [41] conducted the initial
meta-analysis examining the association between
persistent organic pollutants (POPs), specifically
polychlorinated biphenyls (PCBs) and
organochlorine pesticides (OCPs), and the risk of
prostate cancer in the general population. Persistent
organic pollutants (POPs) are a class of chemicals
that have been identified as having the potential to
disrupt the endocrine system. These chemicals are
found in a wide range of food products. The
research conducted revealed that both combinations
of chemicals and individual compounds were
associated with an elevated susceptibility to prostate
cancer.
Given the challenges and financial
implications associated with conducting human
cohort studies, researchers choose to employ a case-
control study design for human epidemiological
investigations. This alternative approach offers
advantages such as reduced costs and time
requirements. Identifying the precise timing of
sickness exposure in case-control studies can
present challenges [38]. However, a case-control
analysis revealed a curvilinear association between
oxychlordane and organochlorine pesticides,
characterised by an inverted u-shape correlation.
Additionally, some PCBs had linear positive
associations with the likelihood of developing
prostate cancer [42, 43].
MOLECULAR SCIENCES AND APPLICATIONS
DOI: 10.37394/232023.2023.3.2
Odangowei Inetiminebi Ogidi,
Akpofiniere Monica Tawariowei
E-ISSN: 2732-9992
8
Volume 3, 2023
3.2 Roles of Endocrine Disrupting Chemicals
in Thyroid Cancer
Both in the United States and around the world, the
incidence of thyroid cancer has been progressively
rising in recent decades. Though a portion of this
increase may be explained by the early or accidental
detection of smaller tumours as a result of more
frequent and sophisticated imaging equipment use
[44], Environmental pollution exposure has been
linked to this phenomenon, according to research.
According to a number of studies, exposure to
certain endocrine disrupting chemicals (EDCs)
alters thyroid function and is linked to a higher risk
of a number of harmful health effects, including
thyroid problems, developmental abnormalities, and
different types of cancer [44]. Pesticides, flame
retardants, phthalates, perfluoroalkyl substances
(PFAS), and bisphenol A are examples of endocrine
disrupting compounds [45].
Thyroid cancer may develop from para-
follicular or follicular thyroid cells. Follicular cell-
derived carcinomas can be divided into five
categories: (1) Papillary thyroid cancer (PTC),
which accounts for 75–85% of cases and frequently
has an excellent prognosis; (2) Follicular thyroid
cancer (FTC); (3) Hurtle cell carcinomas (or
oxyphilic cell carcinomas), which are uncommon
and have a prognosis similar to FTC; (4) Poorly
differentiated thyroid cancer (PDTC), a rare form of
thyroid carcinoma that accounts for less than 5% of
cases; About 90% of thyroid tumours, including
papillary and follicular-history pesticides, are
differentiated, and they typically have a good
prognosis [46, 47].
Numerous phthalate kinds are still used in a
wide range of different businesses, including those
that produce cosmetics, paints, food packaging,
cleaning products, and medical devices (such as
coatings for tablets, blood bags and tubes, medicine
packaging, etc.). This is true even though the US
and EU now forbid the use of specific phthalates,
such as di-(2-ethyhexyl) phthalate (DEHP), in
children's toys. The thyroid is one of the primary
organs that phthalates target because of its capacity
to change hormones. However, they do not
accumulate in the body; instead, they are
metabolised and primarily eliminated in the urine
within a few hours or days. Because they are
continuously and over an extended period of time
exposed to by the entire world's population,
phthalates are particularly intriguing endocrine
disrupting substances [48].
Because certain phthalates, most notably
butylbenzyl phthalate (BBP) and DEHP, affect
vascular endothelial growth factor (VEGF), they can
bind to and activate the oestrogen receptor,
angiogenesis, and tumour progression pathways. In
MELN cells (the Melbourne cell model), which
consistently express oestrogen receptor alpha, these
chemicals actually boosted VEGF output [49].
Epidemiological and experimental investigations
have shown that cadmium can impair thyroid gland
function even at very low ambient exposures, both
at the target gland and extragastrointestinal levels.
Cadmium's involvement in autoimmune disorders
and thyroid cancer has been proven [50].
3.3 Role of Endocrine Disrupting Chemicals in
Breast and Uterine Cancer
Estrogen is primarily accountable for the
proliferation of the most common tumours
associated with the female gender, including breast
and uterine malignancies [51]. So, any endocrine-
disrupting compound that has estrogenic properties
could make it more likely that you will get one of
these two types of cancers that depend on oestrogen.
The results of many experiments done on rodents
show how important it is for breast and uterine
cancer to be exposed to endocrine disruptors before
puberty and during foetal development [52, 53].
Modifying the hormonal milieu during pregnancy
and pre-puberty stages can exert detrimental effects
on the morphological and functional aspects of the
uterus and breasts in adulthood [54]. Based on the
somatic mutation theory, most people think that
carcinogenesis happens when genetic changes
happen in the genes that control cell growth,
differentiation, and maturation [55].
Nevertheless, new empirical evidence from
multiple research studies has underscored the
importance of intercellular connections and
interactions with the extracellular matrix.
Disruptions in these processes at the tissue level
have been found to be associated with the
development of malignancies. The concept referred
to as tissue organisation field theory (TOFT) has
been established in the literature [56]. The
involvement of several reciprocal interactions
between the stroma and the epithelium in breast
tissue morphogenesis suggests that the Theory of
MOLECULAR SCIENCES AND APPLICATIONS
DOI: 10.37394/232023.2023.3.2
Odangowei Inetiminebi Ogidi,
Akpofiniere Monica Tawariowei
E-ISSN: 2732-9992
9
Volume 3, 2023
Organisational Field Transformation (TOFT) is a
more plausible explanation for the development of
breast cancer [57]. Throughout pregnancy, the
stroma of the developing mammary gland exhibits
exclusive expression of both oestrogen receptor
alpha and oestrogen receptor beta isoforms [58, 59].
The presence of the estrogen receptor implies that
this specific tissue compartment plays a crucial role
in facilitating optimal breast growth. Consequently,
the occurrence of any disparity in hormonal and
growth factor exposure, which governs the
appropriate development of the stromal and
epithelial tissue in the growing mammary gland, can
potentially result in the development of neoplasia
during adulthood. The link in question is
unequivocally supported by experimental findings
obtained from the study of growing breast tissue in
mice and rats [57]. The most compelling evidence
arises from research that establishes a correlation
between increased incidences of breast cancer and
exposure to pesticides within the agricultural sector.
Atropine, 2,3,7,8-tetrachloridibenzo-p-dioxin
(TCDD or dioxin), and P,P'-
Dichlorodiphenyltrichloroethane (DDE), along with
other substances, are examples of agricultural
pesticides and herbicides that possess estrogenic
qualities. These compounds have the potential to
interfere with the endocrine system and have been
associated with the development of breast cancer
[60].
3.4 Role of Endocrine Disrupting Chemicals and
Ovarian Cancer
Ovarian cancer (OC) is the leading cause of
mortality among gynecologic malignancies
worldwide [61], despite its lack of need for
estrogen. In vitro studies have been conducted to
investigate the impact of distinct endocrine
disruptors on the proliferation and growth of ovarian
cancer cells. According to findings from in vitro
investigations, the proliferation of BG-1 ovarian
cancer cells with oestrogen receptor positivity was
enhanced by various substances, including BPA,
nonylphenol, octylphenol, methoxychlor, and
benzophenone-1 [62, 63].
Hall and Korach [64] found that Genistein,
2,2-bis(phyroxyphenyl)-1,1,1-trichloroethane
(HPTE), and BPA can make ovarian cancer cells
grow by changing how the oestrogen receptor
works. Nevertheless, the findings of this research do
not suggest a causal relationship between exposure
to these medications and susceptibility to ovarian
cancer. Nevertheless, it is conceivable to speculate
on the potential indirect impacts of endocrine-
disrupting substances on the likelihood of ovarian
cancer development, specifically those substances
that exhibit anti-estrogenic effects in the
hypothalamus. These effects can result in
heightened gonadotropin production, which directly
stimulates the ovaries and may influence the
associated risk [65].
3.5 Role of Endocrine Disrupting Chemicals and
Cervical Cancer
Diethylstilbestrol (DES), a synthetic oestrogen used
to prevent miscarriages until 1971, was found to
cause vaginally clear cell adenocarcinoma in women
who were exposed to it while they were still in the
womb [66]. This was the first proof that endocrine-
disrupting chemicals were bad for you. Despite
cervical cancer not being dependent on estrogen,
this statement remains accurate. These observations
have brought attention to the importance of
exposure to hormone-disrupting chemicals during
foetal development and their potential implications
for adult health. The leading cause of cervical
cancer now is infection with the human papilloma
virus [67]. Nevertheless, a recent in vitro
investigation conducted by [68] revealed that
exposure to bisphenol A (BPA) at nanomolar doses
resulted in an elevation in the migratory and
invasion capabilities of cervical cancer cells
(namely Hela, Sitting, and C-33A cells).
Nevertheless, greater investigation is required to
ascertain the potential impact of increased exposure
to estrogenic endocrine-disrupting drugs on the
susceptibility to cervical cancer.
4 Conclusion
Endocrine-disrupting chemicals (EDCs) are
pervasive molecules that are commonly encountered
in various aspects of daily life, encompassing
pesticides, pharmaceutical agents, plasticizers,
personal care items, as well as food goods and food
packaging. The existing body of evidence derived
from epidemiological studies has demonstrated that
numerous endocrine-disrupting chemicals (EDCs)
had the potential to impact the development or
advancement of various cancers. However, the lack
of attention it receives from the general public,
government agencies, and industry participants
MOLECULAR SCIENCES AND APPLICATIONS
DOI: 10.37394/232023.2023.3.2
Odangowei Inetiminebi Ogidi,
Akpofiniere Monica Tawariowei
E-ISSN: 2732-9992
10
Volume 3, 2023
allows it to potentially develop into a public health
issue. It is imperative to conduct an analysis of
enlightenment initiatives and regulatory measures
about endocrine-disrupting chemicals in order to
effectively reduce the potential for hormonal cancer
resulting from exposure to these compounds.
Nevertheless, due to the presence of EDCs
in the environment, further research is required to
comprehensively assess the potential human risk of
cancers resulting from exposure to combinations of
EDCs in the environment. Currently, due to
significant advancements in next-generation
technologies such as genome sequencing,
proteomics, and epigenomics, it is possible to
identify the crucial molecular alterations linked to
exposure to endocrine-disrupting chemicals (EDCs).
These findings can subsequently be utilized to
develop exposure biomarkers with enhanced
sensitivity and specificity. These technologies will
also provide improved evaluation of previous
exposure and anticipation of future dangers, by
considering an individual's genetic profile.
References:
[1] F.W. Schueler, “Sex-hormonal action and
chemical constitution”, Science , Vol. 103,
Issue 2669, 1946, 221-223.
[2] C.K. Lu, R. Toepel, R.A. Irish, D. Fenske,
B. Barr, R. Bravo, Organic diets
significantly lower children's dietary
exposure to organophosphorus
pesticides. Environmental Health
Perspectives, 114 (2), 2006, 260–3.
[3] P.O. Darnerud, S. Atuma, M. Aune, R.
Bjerselius, A. Glynn, K. P. Grawe, W.
Becker, Dietary intake estimations of
organohalogen contaminants (dioxins, PCB,
PBDE and chlorinated pesticides, e.g. DDT)
based on Swedish market basket data. Food
and Chemical Toxicology: An International
Journal Published for the British Industrial
Biological Research Association, 44 (9),
2006, 1597–1606.
[4] L.M. Anderson, A.D. Bhalchandra, N.T.
Fear, E. Roman, Critical windows of
exposure for children’s health: cancer in
human epidemiological studies and
neoplasms in experimental animal models.
Environ Health Perspect, 108(suppl 3),
2000, 573–594.
[5] E. Diamanti-Kandarakis, E. Palioura, S.A.
Kandarakis, M. Koutsilieris, The impact of
endocrine disruptors on endocrine targets.
Horm Metab Res. 42, 2010, 543–552.
[6] L. Rylander, A. Rignell-Hydbom, H.
Tinnnerbery, B.A.G. Jõnsson, Trends in
human concentration of endocrine
disruptors: Possible reason and
consequences. Journal of Epidemiology and
Community Health, 68(1), 2014, 4-5.
[7] D. Crews, J.A. McLachlan, Epigenetics,
evolution, endocrine disruption, health, and
disease. Endocrinology. 147 (Suppl 6),
2006, S4–S10.
[8] M.B. Macon, S.E. Fenton, Endocrine
disruptors and the breast: Early life effects
and later life disease. J Mammary Gland
Biol Neoplasia. 18, 2013, 43–61.
[9] C. Porte, G. Janer, L. Lorusso, M. Ortiz-
Zarragoitia, M. Cajaraville, M. Fossi,
Endocrine disruptors in marine organisms,
approaches and perspectives. Comp
BiochemPhysiol C ToxicolPharmacol, 143,
2006, 303– 15.
[10] A.M. Calafat, L.L. Needham, Human
exposures and body burdens of endocrine-
disrupting chemicals. In: Endocrine-
Disrupting Chemicals. Humana Press,
2007, 253–268.
[11] G.K. Malhotra, X. Zhao, H. Band, V, Band,
Histological, molecular and functional
subtypes of breast cancers. Cancer Biol.
Ther, 10, 2010, 955–960.
[12] C.M. Perou, T. Sørlie, M.B. Eisen, M. van
de Rijn, S.S. Jeffrey, C.A. Rees, J.R.
Pollack, D.T. Ross, H. Johnsen, L.A.
Akslen, Molecular portraits of human breast
tumours. Nature, 406, 2000, 747–752.
[13] E.A. Rakha, A.R. Green, Molecular
classification of breast cancer: What the
pathologist needs to know. Pathology, 49,
2017, 111–119.
[14] B.D. Lehmann, J.A. Bauer, X. Chen, M.E.
Sanders, A.B. Chakravarthy, Y. Shyr, J.A.
Pietenpol, Identification of human triple-
negative breast cancer subtypes and
preclinical models for selection of targeted
therapies. J. Clin. Investig., 121, 2011,
2750–2767.
[15] N. Howlader, S.F. Altekruse, C.I. Li, V.W.
Chen, C.A. Clarke, L.A.G. Ries, K.A.
Cronin, US incidence of breast cancer
subtypes defined by joint hormone receptor
and HER2 status. J. Natl. Cancer Inst,106,
2014, 055.
[16] American Cancer Society, Treating Breast
Cancer. Available online:
MOLECULAR SCIENCES AND APPLICATIONS
DOI: 10.37394/232023.2023.3.2
Odangowei Inetiminebi Ogidi,
Akpofiniere Monica Tawariowei
E-ISSN: 2732-9992
11
Volume 3, 2023
https://www.cancer.org/cancer/breast-
cancer/treatment.html (accessed on 15
September 2021). 2019
[17] A.S. Heimes, M. Schmidt, Atezolizumab for
the treatment of triple-negative breast
cancer. Expert Opin. Investig. Drugs, 28,
2019, 1–5.
[18] M.E. Barnard, C.E. Boeke, R.M. Tamimi,
Established breast cancer risk factors and
risk of intrinsic tumorsubtypes. Biochim.
Biophys. Acta Rev. Cancer, 1856, 2015, 73–
85.
[19] N. Hamajima, K. Hirose, K. Tajima, T.
Rohan, C.M. Friedenreich, E.E. Calle, A.
Fukao, Menarche, menopause, and breast
cancer risk: Individual participant meta-
analysis, including 118 964 women
withbreast cancer from 117 epidemiological
studies. Lancet Oncol. 13, 2012, 1141–
1151.
[20] F. Clavel-Chapelon, M. Gerber,
Reproductive factors and breast cancer risk.
Do they differ according to ageat diagnosis?
Breast Cancer Res. Treat., 72, 2002, 107–
115.
[21] M, Unar-Munguía, G, Torres-Mejía, M.A.
Colchero, T. González de Cosío,
Breastfeeding Mode and Risk of Breast
Cancer: A Dose-Response Meta-Analysis.
J. Hum. Lact, 33, 2017, 422–434.
[22] G.K. Reeves, K. Pirie, V. Beral, J. Green, E.
Spencer, D. Bull, Cancer incidence and
mortality in relation to body mass index in
the Million Women Study: Cohort study.
Br. Med. J, 335, 2007, 1134–1145.
[23] A.J. Abdelwahab Yousef, Male Breast
Cancer: Epidemiology and Risk Factors.
Semin. Oncol. 44, 2017, 267–272.
[24] C.L. Walker, Mini review: Epigenomic
Plasticity and Vulnerability to EDC
Exposures. Mol. Endocrinol, 30, 2016, 848–
855.
[25] A. Hermann, H. Gowher, A. Jeltsch,
Biochemistry and biology of mammalian
DNA methyltransferases. Cell. Mol. Life
Sci. 61, 2004, 2571–2587.
[26] Y. Yamagata, H. Asada, I. Tamura, L. Lee,
R. Maekawa, K. Taniguchi, T. Taketani, A.
Matsuoka, H. Tamura, N. Sugino, DNA
methyltransferase expression in the human
endometrium: Down-regulation by
progesterone and estrogen. Hum. Reprod.
24, 2009, 1126–1132.
[27] A.M. Zama, M. Uzumcu, Fetal and neonatal
exposure to the endocrine disruptor
methoxychlor causes epigenetic alterations
in adult ovarian genes. Endocrinology, 150,
2009, 4681–4691.
[28] V.P. Zhdanov, Conditions of appreciable
influence of microRNA on a large number
of target mRNAs.Mol. BioSyst, 5, 2009,
638–643.
[29] G. Maillot, M. Lacroix-Triki, S. Pierredon,
L. Gratadou, S. Schmidt, V. Bénès, H.
Roché, F. Dalenc, D. Auboeuf, S. Millevoi,
Widespread estrogen-dependent repression
of micrornas involved in breast tumor cell
growth. Cancer Res. 69, 2009, 8332–8340.
[30] S.L. Tilghman, M.R. Bratton, H.C. Segar,
E.C. Martin, L.V. Rhodes, M. Li, J.A.
McLachlan, T.E. Wiese, K.P. Nephew,
M.E. Burow, Endocrine disruptor regulation
of microRNA expression in breast
carcinoma cells. PLoS ONE, 7, 2012,
e32754.
[31] H. Kawaguchi, N. Miyoshi, Y. Miyamoto,
M. Souda, Y. Umekita, N. Yasuda, H.
Yoshida, Effects of fetalexposure to
diethylstilbestrol on mammary
tumorigenesis in rats. J. Vet. Med. Sci. 71,
2009, 1599–1608.
[32] International Agency for Research on
Cancer (IARC), Monographs on the
Evaluation of Carcinogenic to Humans:
Radiation. IARC Monogr. Eval. Carcinog.
Risks Hum, 75, 2012, 103–210.
[33] International Agency for Research on
Cancer (IARC), Monographs on the
Evaluation of Carcinogenic to Humans:
Diethylstilbestrol. IARC Monogr. Eval.
Carcinog. Risks Hum, 21, 2012, 175–218.
[34] M.F. Sweeny, N. Sweeney, A.M. Hasan,
A.M. Soto, C. Sonnenschein,
Environmental endocrine disruptors: effects
on the human male reproductive system.
Rev. Endocr. Metab. Disord, 16, 2015, 341-
357.
[35] L.G. Kahnet, C. Kahn, S.F. Philippat, R.
Nakayama, L. Slama, N. Trasande,
Endocrine-disrupting chemicals:
implications for human health.Lancet
Diabetes Endocrinol, 8, 2020, 703-718.
[36] J.E. Lim, C. Nam, J. Yang, K.H. Rha, K.M.
Lim, S.H. Jee, Serum persistent organic
pollutants (POPs) and prostate cancer risk:
A case-cohort study. Int. J. Hyg. Environ.
Health, 220, 2017, 849–856.
[37] B. Eskenazi, A. Bradman, R. Castorina,
Exposures of children to organophosphate
pesticides and their potential adverse health
MOLECULAR SCIENCES AND APPLICATIONS
DOI: 10.37394/232023.2023.3.2
Odangowei Inetiminebi Ogidi,
Akpofiniere Monica Tawariowei
E-ISSN: 2732-9992
12
Volume 3, 2023
effects. Environ. Health Perspect, 107,
1999, 409–419.
[38] C.V. Rider, J.R. Furr, V.S. Wilson, L.E.
Gray, Cumulative effects of in utero
administration of mixtures of reproductive
toxicants that disrupt common target tissues
via diverse mechanisms of toxicity. Int. J.
Androl, 33, 2010, 443–462.
[39] D.E. Irwin, I. Milsom, Z. Kopp, P. Abrams,
W. Artibani, S. Herschorn, Prevalence,
severity, and symptom bother of lower
urinary tract symptoms among men in the
EPIC study: Impact of overactive
bladder. Eur. Urol. 56, 2009, 14–20.
[40] H.M. Scott, J.I. Mason, R.M. Sharpe,
Steroidogenesis in the fetal testis and its
susceptibility to disruption by exogenous
compounds. Endocr. Rev, 30, 2009, 883–
925.
[41] J.E. Lim, S.H. Park, S.H. Jee, H. Park,
Body concentrations of persistent organic
pollutants and prostate cancer: A meta-
analysis. Environ. Sci. Pollut. Res. Int. 22,
2015,11275–11284.
[42] R. Capocaccia, R. Foschi, A. Zucchetto, R.
Valdagni, N. Nicolai, M. Maffezzini, G.
Gatta, Estimates of prostate cancer burden
in Italy. Cancer Epidemiol, 40, 2016, 166–
172.
[43] J.M. Ritchie, S.L. Vial, L.F. Fuortes, H.
Guo, V.E. Reedy, E.M. Smith,
Organochlorines and risk of prostate
cancer. J. Occup. Environ. Med, 45, 2003,
692–702.
[44] R.T. Zoeller, T.R. Brown, L.L. Doan,
Endocrine disrupting chemicals and public
health protection: a statement of principles
from the endocrine society. Endocrinology,
153(9), 2012, 4097-4110.
[45] A.M. Soto, C. Sonnenschein,
Environmental causes of cancer: Endocrine
disruptors as carcinogens. Nat. Rev.
Endocrinol. 6, 2010, 363–370.
[46] I.C. Nettore, A. Colao, P.E. Macchia,
Nutritional and Environmental Factors in
Thyroid Carcinogenesis. Int. J. Environ.
Res. Public Health, 15, 2018, 1735.
[47] M.E. Cabanillas, D.G. McFadden, C.
Durante, Thyroid cancer. Lancet. 388, 2016,
2783–2795.
[48] A. Colao, G. Muscogiuri, P. Piscitelli,
Environment and Health: Not Only
Cancer. Int. J. Environ. Res. Public Health.
13, 2016, 724.
[49] P. Zuccarello, G. Oliveri Conti, F.
Cavallaro, C. Copat, A. Cristaldi, M. Fiore,
M. Ferrante, Implication of dietary
phthalates in breast cancer. A systematic
review. Food Chem. Toxicol, 118, 2018,
667–674.
[50] A. Buha, V. Matović, B. Antonijevic, Z.
Bulat, M. Čurćić, E.A. Renieri, A.M.
Tsatsakis, A. Schweitzer, D. Wallace,
Overview of Cadmium Thyroid Disrupting
Effects and Mechanisms. Int. J. Mol.
Sci. 19, 2018, 1501.
[51] T.J. Key, Hormones and cancer in
humans. Mutat Res. 333(1-2), 1995, 59–67.
[52] T. Mori, H. Nagasawa, H.A. Bern, Long-
term effects of perinatal exposure to
hormones on normal and neoplastic
mammary growth in rodents: a review. J
Environ Pathol Toxicol. 3(1-2), 1979, 191–
205.
[53] A. Albini, C. Rosano, G. Angelini, A.
Amaro, A.I. Esposito, S. Maramotti,
Exogenous hormonal regulation in breast
cancer cells by phytoestrogens and
endocrine disruptors. Curr Med Chem.
21(9), 2014, 1129-1145.
[54] D.A. Crain, S.J. Janssen, T.M. Edwards, J.
Heindel, S.M. Ho, P. Hunt, Female
reproductive disorders: the roles of
endocrine-disrupting compounds and
developmental timing. Fertil Steril. 90(4),
2008, 911–940. (2008)
[55] D. Hanahan, R.A. Weinberg, Hallmarks of
cancer: the next generation. Cell. 144(5),
2011, 646–674.
[56] A.M. Soto, C. Sonnenschein, The tissue
organization field theory of cancer: a
testable replacement for the somatic
mutation theory. BioEssays: News Rev Mol
Cell Dev Biol. 33(5), 2011, 332–340.
[57] M.D. Sternlicht, H. Kouros-Mehr, P. Lu, Z.
Werb, Hormonal and local control of
mammary branching
morphogenesis. Differentiation: Res Biol
Divers.74(7), 2006, 365–381.
[58] P.R. Wadia, N.J. Cabaton, M.D. Borrero,
B.S. Rubin, C. Sonnenschein, T. Shioda,
Low-dose BPA exposure alters the
mesenchymal and epithelial transcriptomes
of the mouse fetal mammary gland. PLoS
One, 8(5), 2013, e63902.
[59] J.G. Lemmen, J. L. Broekhof, G.G. Kuiper,
J.A. Gustafsson, P.T. van der Saag B. van
der Burg, Expression of estrogen receptor
alpha and beta during mouse
MOLECULAR SCIENCES AND APPLICATIONS
DOI: 10.37394/232023.2023.3.2
Odangowei Inetiminebi Ogidi,
Akpofiniere Monica Tawariowei
E-ISSN: 2732-9992
13
Volume 3, 2023
embryogenesis. Mech Dev. 81(1),
1999,163–167.
[60] S.M. Snedeker, Pesticides and breast cancer
risk: A review of DDT, DDE, and
dieldrin. Environmental Health
Perspectives, 109 (Suppl 1), 2001, 35–47.
(2001)
[61] L.A. Torre, F. Bray, R.L. Siegel, J. Ferlay,
J. Lortet-Tieulent, A. Jemal, Global cancer
statistics, 2012. CA Cancer J Clin. 65(2),
2015, 87-108.
[62] S.H. Park, K.Y. Kim, B.S. An, Cell growth
of ovarian cancer cells is stimulated by
xenoestrogens through an
estrogendependent pathway, but their
stimulation of cell growth appears not to be
involved in the activation of the
mitogenactivated protein kinases ERK-1
and p38. J Reprod Dev. 55(1), 2009, 23-29.
[63] M.A. Park, K.A. Hwang, H.R. Lee, B.R. Yi,
E.B. Jeung, K.C. Choi, Benzophenone-1
stimulated the growth of BG-1 ovarian
cancer cells by cell cycle regulation via an
estrogen receptor alphamediated signaling
pathway in cellular and xenograft mouse
models. Toxicology.305, 2013, 41-48.
[64] J.M. Hal, K.S Korach, Endocrine disrupting
chemicals promote the growth of ovarian
cancer cells via the ER-CXCL 12-CXCR4
signaling axis. MolCarcinog. 52(9), 2013,
715-725.
[65] F. Tomao, G.L. Russo, G.P. Spinelli,
Fertility drugs, reproductive strategies and
ovarian cancer risk. J Ovarian Res, 7, 2014,
51.
[66] D.L. Barclay, Congenital diethylstilbestrol-
associated vaginal/cervical adenosis (DES
babies) J Ark Med Soc. 75(12), 1979, 451–
452.
[67] L. Thaxton, A.G. Waxman, Cervical cancer
prevention: immunization and screening
2015. Med Clin North Am. 99(3), 2015,
469–477.
[68] X.F. Ma, J. Zhang, H.L. Shuai, B.Z. Guan,
X. Luo, R.L. Yan, IKKbeta/NF-kappaB
mediated the low doses of bisphenol A
induced migration of cervical cancer
cells. Arch BiochemBiophys. 573, 2015, 52–
58.
Contribution of Individual Authors to the
Creation of a Scientific Article (Ghostwriting
Policy)
Odangowei Inetiminebi Ogidi: was responsible
for the conceptualization, validation, writing -
original draft and actively participated in all the
publication stages of this manuscript.
Akpofiniere Monica Tawariowei: was
responsible for reviewing and editing the
manuscript and actively participated in all the
publication stages of this manuscript.
Sources of Funding for Research Presented in a
Scientific Article or Scientific Article Itself
No funding was received for conducting this study.
Conflict of Interest
The authors have no conflicts of interest to declare
that are relevant to the content of this article.
Creative Commons Attribution License 4.0
(Attribution 4.0 International, CC BY 4.0)
This article is published under the terms of the
Creative Commons Attribution License 4.0
https://creativecommons.org/licenses/by/4.0/deed.en
_US
MOLECULAR SCIENCES AND APPLICATIONS
DOI: 10.37394/232023.2023.3.2
Odangowei Inetiminebi Ogidi,
Akpofiniere Monica Tawariowei
E-ISSN: 2732-9992
14
Volume 3, 2023
