BERKELEY, CA (UroToday.com) - Among men in the U.S., prostate cancer is the most commonly diagnosed malignancy and is the second leading cause of cancer-related deaths. In addition to age, race, and family history, emerging evidence indicates that environmental pollutants may be important risk factors for prostate cancer. Endocrine disruptors such as bisphenol A (BPA), mimicking the action of estrogen, are especially relevant for organs such as the prostate. Indeed, increased estrogen levels during aging have been implicated in prostate cancer development in animals for some time.[3, 4]
World production capacity of BPA has increased from 1 million tons in the 1980s to more than 2.2 million tons in 2009. The major route of exposure to BPA is diet. BPA leaches out from the lining of food and beverage cans. According to the Centers for Disease Control bisphenol A is present in the urine of 93% of children and adults tested in 2003–2004. A study in 2011 found that participants who ate canned soup for 5 days experienced more than a 1,000 percent increase in urinary BPA levels, compared to when they dined on fresh soup. In addition to diet, exposure can also occur through the skin through absorption. This is alarming since BPA is found in high concentration in thermal paper and carbonless copy paper. Popular uses of thermal paper include money bills, receipts, event and cinema tickets, labels, and airline tickets. Exposure through contact with thermal paper is significant for the general population and can be higher for those with frequent occupational contact. In short, we are surrounded by an environment rich in BPA.
BPA is not a recognized carcinogen, but its carcinogenic effects can be mediated by its action as an endocrine disrupting chemical (EDC). Because of the widespread exposure to BPA in our daily lives, it is time to stop ignoring the effects of BPA on health, and to resolve whether BPA is causing adverse health outcomes in humans. We recently conducted a clinical study on 60 patients admitted to the urology clinic at the University of Cincinnati Medical Center. The BPA levels in the urine of the prostate cancer patients were found to be higher (geometric mean 5.74 µg/g creatine) than in the urine of the non-prostate cancer patients (1.43 µg/g creatine. Interestingly, the difference in BPA levels in urine was even more apparent in the younger patients (< 65 years of age) when compared to older patients. Since BPA has a relatively rapid clearance rate and a single exposure is usually removed from the body within 24 hours, individuals with high urinary BPA likely have a lifestyle that is conducive to frequent exposure. From these data we can make two posits: (a) they suggest that higher BPA exposure may promote early onset of prostate cancer either by promoting initiation or progression, and (b) since BPA has now been in commercial use for 57 years and hence, younger patients would have been theoretically exposed to BPA prepuberty, and the concept of developmental origin of cancer may explain their apparent higher susceptibility.
While this study involves a small population (total of 60 patients), it follows a large body of animal-based research that substantiates this result. For example, transient developmental exposure of rats to low, environmentally relevant doses of BPA or estradiol was found to increase rat prostate gland susceptibility to adult-onset precancerous lesions and cancer. Moreover, a recent study examined the BPA susceptibility of human epithelial stem-like cells grafted into rats. Rats exposed to early life BPA had a 33% incidence of precancerous lesions and adenocarcinoma in the grafted tissue, compared to oil fed controls (13% incidence). Hence, evidence is fast accumulating that certain EDCs can promote prostate cancer development, especially relevant to the early onset disease.
Our results that BPA levels in the urine of prostate cancer patients were higher than in the non-prostate cancer patients is especially alarming considering that in 2012, approximately 10% of the 241 740 men diagnosed with prostate cancer had early-onset disease. This is relevant since men diagnosed at a young age with high-grade and advanced-stage prostate cancer have a higher cause-specific mortality than men diagnosed at an older age. Additionally, though the majority of men with early-onset prostate cancer exhibit low-risk disease at diagnosis, because of the extended life expectancy of these patients, the chances of disease progression leading to death from prostate cancer are greater for this group.
Moreover, one must bear in mind that the prostate is not the only entity susceptible to BPA. A positive association has been found between postnatal urinary BPA concentrations and asthma in children. Additionally, urinary BPA concentration has been shown to be associated with obesity in children and adolescents, with risk to breast cancer, infertility, recurrent miscarriage, endometrial disorders, thyroid function, and increased type-2 diabetes, to name a few.
Finally, considering the replacement of BPA in plastic containers, bottles, receipts and toys, it is important to note that there is mounting evidence that some of the BPA analogues might be as detrimental to human health as BPA. For example, BPA analogues such as bisphenol S, bisphenol F, tetrachlorobisphenol A (TCBPA), and tetrabromobisphenol A (TBBPA) were found to disrupt multiple nuclear receptors and may therefore interfere with the endocrine system. In vitro studies on steroidogenesis, receptor activity, and biomarkers of effects indicated that interference with the endocrine system was the predominant effect of the test compounds bisphenol B, bisphenol E, bisphenol F, bisphenol S and 4-cumylphenol. Moreover, developmental exposure of zebrafish to bisphenol-S impaired their subsequent reproduction potential and hormonal balance when adult. Bisphenol S also disrupts membrane-initiated estradiol-induced cell signaling, leading to altered cell proliferation, cell death, and PRL release in a rat pituitary cell line.
These studies ring a bell of alarm, indicating that a substitution of BPA with these structural analogues should be carried out with great caution.
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Shuk-mei Ho and Pheruza Tarapore as part of Beyond the Abstract on UroToday.com. This initiative offers a method of publishing for the professional urology community. Authors are given an opportunity to expand on the circumstances, limitations etc... of their research by referencing the published abstract.
Department of Environmental Health, University of Cincinnati Medical Center, Cincinnati, OH USA, and Cincinnati Cancer Center, Cincinnati, OH USA