Cancer as development gone awry: the case for bisphenol-A as a carcinogen

2011 ◽  
Vol 2 (1) ◽  
pp. 9-16 ◽  
Author(s):  
C. Sonnenschein ◽  
P. R. Wadia ◽  
B. S. Rubin ◽  
A. M. Soto
Keyword(s):  
Breast Cancer ◽  
Bisphenol A ◽  
Developmental Plasticity ◽  
Empirical Support ◽  
Epidemiological Data ◽  
Additional Treatment ◽  
Tissue Organization ◽  
Estrogen Exposure ◽  
Tissue Organization Field Theory ◽  
Neoplastic Lesions

The discovery of a rare clear cell carcinoma of the vagina in young women gestationally exposed to the estrogen diethylstilbestrol (DES) lent empirical support to the hypothesis that prenatal exposure to xenoestrogens might cause cancer. This fact contradicted two well-accepted notions: (i) mammalian development was merely the unfolding of a genetic program and (ii) only mutagenic agents could cause cancer. The ecological developmental biology (eco–devo) movement revitalized the concept of developmental plasticity through the occurrence of polyphenisms whereby a single genotype produces diverse phenotypes which are determined by environmental cues. Based on the principles of eco–devo and the tissue organization field theory of carcinogenesis, we hypothesized that developmental exposure to xenoestrogens increased the propensity to develop mammary cancer during adulthood. Bisphenol-A (BPA), a ubiquitous xenoestrogen, was chosen as a model for environmental estrogen exposure. In mice, perinatal exposure to environmentally relevant BPA levels induced alterations of the mammary gland architecture which manifested during fetal morphogenesis and throughout life, including the development of pre-neoplastic lesions. In rats, gestational exposure to BPA induced pre-neoplastic lesions and carcinoma in situ that manifested in adulthood in the absence of any additional treatment. Emerging epidemiological data reveal an increased incidence of breast cancer in women exposed to DES during gestation. Hence, both animal experiments and epidemiological data strengthen the hypothesis that fetal exposure to xenoestrogens may be an underlying cause of the increased incidence of breast cancer observed over the past 50 years.

ER, PR & HER2 Receptor status in recurrent breast cancer: Its relation to age & time of recurrence

2020 ◽  
Vol 22 (1) ◽  
pp. 16-20
Author(s):  
Abu Khaled Muhammad Iqbal ◽  
Nasima Akhter ◽  
Hasan Shahrear Ahmed ◽  
Md Rassell ◽  
AMM Yahia ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Treatment Approach ◽  
Recurrent Breast Cancer ◽  
Breast Cancer Patients ◽  
Her2 Receptor ◽  
Younger Patients ◽  
Receptor Status ◽  
Increased Risk ◽  
Neoplastic Lesions ◽  
Recurrent Breast

Background: Malignant neoplastic lesions of the breast are one of the main causes of cancer death among women. In tumor cells the expression status of Estrogen receptor (ER), progesterone receptor (PR), and c-ERBB2 (HER2/neu) are therapeutically and prognostically important markers affecting the treatment approach, management and prognosis of breast carcinoma. Objective: To explore the relation of receptor status in recurrent breast cancer to age and time of recurrence. Methods: This study was conducted in National Institute of Cancer Research and Hospital (NICRH) and included 81 female patients between 20 to 75 years with recurrent breast cancer. Detection of receptor status of ER +ve/-ve, PR +ve/-ve, Her-2+ve/-ve was based on the immunohistochemistry staining of tissue samples of malignant neoplastic lesions prepared from tissue biopsies of patients with recurrent breast cancer. All the information were recorded through the pre-structured data collection sheet and analyzed. Results: This study showed that most of the recurrent breast cancer patients were Triple negative breast cancer (TNBC) (39.5%) and among them most of them were younger patients. Younger patients with TNBC had increased risk of recurrence. Most of the recurrence occurred within 1-2 years. Conclusion: It can be concluded that the assessment of the expression of these biornarkers in recurrent tumors provides reliable information for the treatment approach of locoregional tumors. Journal of Surgical Sciences (2018) Vol. 22 (1): 16-20

scholarly journals Bisphenol A Inhibits the Transporter Function of the Blood-Brain Barrier by Directly Interacting with the ABC Transporter Breast Cancer Resistance Protein (BCRP)

2021 ◽  
Vol 22 (11) ◽  
pp. 5534
Author(s):  
Elin Engdahl ◽  
Maarten van Schijndel ◽  
Dimitrios Voulgaris ◽  
Michela Di Criscio ◽  
Kerry Ramsbottom ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Bisphenol A ◽  
Blood Brain Barrier ◽  
Breast Cancer Resistance Protein ◽  
Brain Barrier ◽  
Production Volume ◽  
Cancer Resistance ◽  
Blood Brain ◽  
Resistance Protein

The breast cancer resistance protein (BCRP) is an important efflux transporter in the blood-brain barrier (BBB), protecting the brain from a wide range of substances. In this study, we investigated if BCRP function is affected by bisphenol A (BPA), a high production volume chemical used in common consumer products, as well as by bisphenol F (BPF) and bisphenol S (BPS), which are used to substitute BPA. We employed a transwell-based in vitro cell model of iPSC-derived brain microvascular endothelial cells, where BCRP function was assessed by measuring the intracellular accumulation of its substrate Hoechst 33342. Additionally, we used in silico modelling to predict if the bisphenols could directly interact with BCRP. Our results showed that BPA significantly inhibits the transport function of BCRP. Additionally, BPA was predicted to bind to the cavity that is targeted by known BCRP inhibitors. Taken together, our findings demonstrate that BPA inhibits BCRP function in vitro, probably by direct interaction with the transporter. This effect might contribute to BPA’s known impact on neurodevelopment.

scholarly journals Gene-Environment Interactions Relevant to Estrogen and Risk of Breast Cancer: Can Gene-Environment Interactions Be Detected Only among Candidate SNPs from Genome-Wide Association Studies?

Cancers ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 2370
Author(s):  
JooYong Park ◽  
Ji-Yeob Choi ◽  
Jaesung Choi ◽  
Seokang Chung ◽  
Nan Song ◽  
...  
Keyword(s):  
Breast Cancer ◽  
High Risk ◽  
Environmental Factors ◽  
Minor Allele ◽  
Estrogen Metabolism ◽  
Age At Menarche ◽  
Genome Wide Association Studies ◽  
Estrogen Exposure ◽  
Gene Environment ◽  
Independent Population

In this study we aim to examine gene–environment interactions (GxEs) between genes involved with estrogen metabolism and environmental factors related to estrogen exposure. GxE analyses were conducted with 1970 Korean breast cancer cases and 2052 controls in the case-control study, the Seoul Breast Cancer Study (SEBCS). A total of 11,555 SNPs from the 137 candidate genes were included in the GxE analyses with eight established environmental factors. A replication test was conducted by using an independent population from the Breast Cancer Association Consortium (BCAC), with 62,485 Europeans and 9047 Asians. The GxE tests were performed by using two-step methods in GxEScan software. Two interactions were found in the SEBCS. The first interaction was shown between rs13035764 of NCOA1 and age at menarche in the GE|2df model (p-2df = 1.2 × 10−3). The age at menarche before 14 years old was associated with the high risk of breast cancer, and the risk was higher when subjects had homozygous minor allele G. The second GxE was shown between rs851998 near ESR1 and height in the GE|2df model (p-2df = 1.1 × 10−4). Height taller than 160 cm was associated with a high risk of breast cancer, and the risk increased when the minor allele was added. The findings were not replicated in the BCAC. These results would suggest specificity in Koreans for breast cancer risk.

scholarly journals Manfaat Progressive Muscle Relaxation (PMR) sebagai intervensi keperawatan dalam meningkatkan Quality of Life (QOL) wanita kanker payudara yang menjalani kemoterapi

2019 ◽  
Vol 2 (1) ◽  
Author(s):  
Anastasia Diah Larasati ◽  
Anggorowati Anggorowati ◽  
Andrew Johan
Keyword(s):  
Breast Cancer ◽  
Quality Of Life ◽  
Stress Reduction ◽  
Muscle Relaxation ◽  
Epidemiological Data ◽  
Review Literature ◽  
Progressive Muscle Relaxation ◽  
Literature Study ◽  
Patient Will

Based on epidemiological data, the incidence recorded globally by theInternational Agency for Research On Cancer (IARC) in 2012, as many as 43.3women had breast cancer. The patient will undergoing chemotherapy andexperience various disturbing symptoms. Various complaints can affect QOL.One of the therapies recommended by the journal Oncology Nursing is thetherapy of Progressive Muscle Relaxation (PMR).Objective: To find out the benefits of PMR as one of the nursing interventions indealing with the quality of life for women Ca. Mammae is undergoingchemotherapyThe method used in this paper is a review literature study. Databases used insource search are CINAHL, PubMed, Science Direct, and Medline. The criterionof inclusion in literature search is the year of article publishing starting in 2010until 2018, and the English full article. Search keywords are Progressive MuscleRelaxation, breast cancer, quality of life and chemotherapy. Literature analysisuses PICOT (Population, Intervention, Comparison, Outcome, and Time).Based on the analysis found 5 themes, namely the quality of life characteristicsof patients undergoing chemotherapy, PMR as a relaxation therapy, PMR as apsychological stress reduction intervention, PMR as an intervention to increasemuscle metabolism, and PMR as a pain reduction intervention.Patients who undergoing chemotherapy will experience a decrease in QOL. PMRis a recommended intervention to improve patient QOL.

scholarly journals Estrogen-independent molecular actions of mutant estrogen receptor alpha in endometrial cancer

2018 ◽  
Author(s):  
Zannel Blanchard ◽  
Jeffery M. Vahrenkamp ◽  
Kristofer C. Berrett ◽  
Spencer Arnesen ◽  
Jason Gertz
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Endometrial Cancer ◽  
Cancer Cells ◽  
Estrogen Receptor Alpha ◽  
Chromatin Accessibility ◽  
Large Set ◽  
Regulatory Changes ◽  
Estrogen Exposure ◽  
Independent Mutant

AbstractEstrogen receptor 1 (ESR1) mutations have been identified in hormone therapy resistant breast cancer and primary endometrial cancer. Analyses in breast cancer suggests that mutant ESR1 exhibits estrogen independent activity. In endometrial cancer, ESR1 mutations are associated with worse outcomes and less obesity, however experimental investigation of these mutations has not been performed. Using a unique CRISPR/Cas9 strategy, we introduced the D538G mutation, a common endometrial cancer mutation that alters the ligand binding domain of ESR1, while epitope tagging the endogenous locus. We discovered estrogen-independent mutant ESR1 genomic binding that is significantly altered from wildtype ESR1. The D538G mutation impacted expression, including a large set of non-estrogen regulated genes, and chromatin accessibility, with most affected loci bound by mutant ESR1. Mutant ESR1 is unique from constitutive ESR1 activity as mutant-specific changes are not recapitulated with prolonged estrogen exposure. Overall, D538G mutant ESR1 confers estrogen-independent activity while causing additional regulatory changes in endometrial cancer cells that are distinct from breast cancer cells.

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