Going Bananas Over a Bug Provides New Insights into How Prostate Cancer Develops

I’ve never been to the French West Indies, and I’ve never heard of the banana root borer (a larvae which tunnels through banana corms- admit it, you were wondering!), but this little critter has sparked some insightful research into what causes prostate cancer.

Unlike other cancers, little is known about the risk factors for prostate cancer with increasing age, ethnicity (Afro-Carribean men have an increased risk of prostate cancer for example) and family history of the disease being the only known risk factors.

The key drivers of prostate cancer development are androgens which bind the androgen receptor (AR) in prostate cancer cells and promote tumor development; however, estrogens are also thought to be involved as estrogen receptors (ERs) have been found in the prostate and in vitro studies have shown that binding of estrogens or estrogen-like molecules (also known as endocrine disruptors) to these receptors (ER alpha and beta) can result in prostate cancer development in tumor models.

Chlordecone (also known as Kepone) is an insecticide which has estrogenic-like properties in that it can bind ER alpha and beta and therefore has similar physiological properties to estrogen. Notably, the incidence of prostate cancer is particularly high in the French West Indies, where chlordecone was used for over 30 years to kill the banana root borer larvae.

Based on these findings, Luc Multigner and colleagues from Universitaire de la Guadeloupe in the French West Indies, measured exposure to chlordecone by measuring it’s concentration in the serum of 623 prostate cancer patients and 721 control patients exposured to this agent for over 30 years and found that it was consistently associated with an increased risk of prostate cancer. Prostate cancer risk was higher in subjects with a family history of prostate cancer, suggestive of similar patterns of exposure to chlordecone possibly through genetic susceptibility to the toxic effects of this agent. In addition, prostate cancer risk was increased for those men who had lived in Western countries, possibly attributed to lifestyle and nutritional changes which could increase the risk of developing prostate cancer.

The authors hypothesise that chlordecone acts as an ERalpha agonist and an ERbeta antagonist in the prostate. It is unclear how chlordecone exactly causes prostate cancer, but it is thought that the balance between the bad cancer causing effects mediated through ERa (increasing cell proliferation and inflammation) and the good anti-cancer effects (antiproliferative and ant inflammatory) mediated by ERbeta may be tipped in favor of the bad estrogen- ERalpha.

This is the first epidemiologic study to demonstrate a link between between environmental exposure to endocrine disruptors and prostate cancer development, and will heighten the debate surrounding the use of these agents and their potential risks for humans.

Reference: Journal of Clinical Oncology: http://jco.ascopubs.org/cgi/reprint/28/21/3457

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