Breast cancer remains a topic of extensive research at leading academic life science research centers, with new discoveries in the lab shedding light onto how the disease progresses, thus facilitating future treatment options. Recent research performed at The University of Texas at Arlington under the supervision of Subhrangsu Mandal, associate professor of chemistry/biochemistry at the university, and PhD student Arunoday Bhan, has linked the effects of the synthetic chemical compound Bisphenol A (BPA) — a chemical commonly found in plastics — to breast cancer. The study was recently published in the February issue of Journal of Steroid Biochemistry and Molecular Biology, and co-authored by Mandal’s lab members Imran Hussain and Khairul I Ansari, as well as Linda I. Perrotti, a UT Arlington psychology assistant professor, and Samara A.M. Bobzean, a member of Perrotti’s lab.
The main perspective of the study links BPA, a building block of polycarbonate plastic, to tumor genesis and tumor growth. The new findings further add to what is already know about BPA, which has remained a topic of research for its role in tumor initiation for quite a few years now. Studies demonstrating BPA’s ability to manipulate the synthesis of non-coding HOTAIR RNA (found on chromosoe no. 12 in humans) forms the basis of this perspective. HOTAIR RNA in turn has been shown to be present at very high levels in metastatic tumors and carcinomas. HOTAIR does not produce a protein on its own, however, when it is being expressed or functioning, it can suppress genes that would normally slow tumor growth or cause cancer cell death. Apart from breast cancer, esophageal squamous cell carcinoma has also been said to contain high levels of HOTAIR RNA.
Apart from its possible link to breast cancer, BPA has also been studied for its role in prostate cancer, according to recent studies being conducted at the University of Cincinnati and led by Principle investigator Shuk-mei Ho, PhD, who is the director of the Cincinnati Cancer Center and also serves as Jacob G. Schmidlapp Chair of Environmental Health and professor at the University of Cincinnati College of Medicine. Reports from the University of Cincinnati Academic Health Center suggest that levels of BPA have been obtained from urine samples of men affected with prostate cancer. Moreover, a low dose of BPA has been shown to increase centrosome amplification 2 to 8 folds, leading to uncontrolled cell division because of chromosomal mutations caused by these centrosomal abnormalities — which forms the very basis of cancer development.
BPA is an endocrine disruptor that mimics thyroid and estrogen hormones and interferes with hormone regulation. The chemical has been shown to react and disrupt the function of Estrogen Receptors (ER) and Estrogen Receptor Co-regulators (ERC) both in the presence and absence of estrogen. Hence, they easily bind to the promoter elements of HOTAIR RNA segments, to modify chromatin in an unwanted manner, leading to gene activation. BPA is an active component in plastic bottles, food cans, baby feeding bottles, and other common household items. As a result, the chemical has been found to be present in blood of around 90% of Americans.
Another report from a study dating back to June 2012 by Tufts University School of Medicine researchers Ana Soto, Carlos Sonnenschein, and Catherine VandeVoort from the University of California at Davis featured rhesus monkeys who were fed fruits containing tiny amounts of BPA during their gestational period (corresponding to the third trimester of human pregnancy). When compared to monkeys of the same group fed with BPA-less fruits, it was found that the former had advanced developments of their mammary glands, with their newborns having a high density mammary buds. Also, the level of BPA in their blood was similar to that of an average American. This lead to a conclusion by Soto, “This study buttresses previous findings showing that fetal exposure to low xenoestrogen levels causes developmental alterations that in turn increase the risk of mammary cancer later in life.”
A similar chemical, diethylstilbestrol (DES), a hormone regulator and used in pregnancy control, has also been shown to have effects in breast cancer, genital carcinomas, gynaecological tract abnormalities in women and prostate and testicular cancer in men.
According to Prof. Mandal, “Understanding the developmental impact of these synthetic hormones is an important way to protect ourselves and could be important for treatment.”
Despite the evidence uncovered in these recent studies, there have also been conflicting studies that suggest BPA might not have a direct role to play in tumor genesis. As quoted by Shuk-mei Ho of the University of Cincinnati, “However, human studies linking BPA exposure to heightened cancer risk are limited.” Hence, unless conclusive studies are conducted, the direct link between BPA and breast cancer remains debatable.