Study: BPA Exposure in Developing Prostate Increases Later Cancer Risk

Bisphenol A (BPA) is a chemical used to make plastics and has been used in commercial products for more than 50 years. BPA is found in plastic food storage containers, water bottles, and the lining of canned goods, among other products. BPA is an estrogen mimic; it has been linked to negative health effects.

Back in 2006, Gail Prins, PhD, professor of urology and physiology at the College of Medicine at the University of Illinois in Chicago, and colleagues provided evidence for one of the first direct links between low-dose exposure to BPA during the development of rats and the later development of prostate cancer. Estrogens have been implicated in carcinogenesis, and BPA exposure during prenatal development has been thought to be a culprit in increases in prostate cancer rates.

Now, Prins and colleagues show that early BPA exposure increases the cancer risk in animal models of human prostate cancer. Prins presented the results at the Endocrine Society’s Annual Meeting & Expo in June.

“The most important findings are that the human prostate epithelium responds in a similar manner as previous studies found in rodents,” Prins told Cancer Network. The results show that even low doses of BPA could cause early, subtle changes that can have latent consequences.

“Our findings indicate these early [stem] cells are epigenetically reorganized [upon exposure to BPA] in such a manner that when they ‘see’ estrogens later in life, the response is more robust,” said Prins.

The study shows that the prostate stem and progenitor cells that populate the prostate epithelium become sensitized to estrogens if the cells are exposed to BPA during early development. The BPA acts as a mimic of estrogen in the body; the prostate stem cells, which have a long lifespan, pass on the estrogen sensitivity to their progeny. The level of BPA exposure was similar to what people encounter in their daily lives, suggesting that even this small level could increase prostate cancer risk.

The researchers implanted human prostate stem cells into mice, allowing human prostate tissue to develop. The human stem cells were derived from deceased young organ donors. The mice were fed BPA for 2 weeks during early prostate development to mimic the exposure of the developing prostate gland in humans. The doses given to the mice were the same as those previously measured in pregnant women in the United States. After the human prostate tissue matured in the mice, they were exposed to estrogen for several months. Rising estrogen levels occur in older men and can increase the risk of prostate cancer and can promote progression, previous studies have shown.

“What we found is that the prostate's sensitivity to this cancer-promoting hormone is greatly increased if they saw an inappropriate amount or type of estrogen when the gland is developing,” said Prins. Other endocrine-disrupting chemicals or synthetic estrogens could also cause this to occur.

Thirty-three percent of the mice with human prostate tissue developed signs of prostate cancer (high-grade prostate intraepithelial neoplasia) compared with 12% of the mice who were not initially exposed to BPA, but were exposed to estrogen later. This difference was statistically significant (P < .05). The proportion of mice that had prostate cancer went up to 45% if the original human prostate stem cells were exposed to BPA before being implanted into the mice (P < .01).

Prins said she was surprised to learn that early-stage human prostate progenitor cells express estrogen receptors and are direct estrogen targets. She and colleagues are now dissecting the molecular mechanisms that could trigger reprogramming of the prostate stem cells in response to BPA.

Prins believes that the results may have implications for men with prostate cancer exposed to BPA. “Prostate cancer cells can directly respond to BPA with increased growth. So it may not just be early life exposures that we are concerned about, but exposures to these chemicals if one already has a cancerous disease or other adverse health status.”