Untangling the association between environmental endocrine disruptive chemicals and the etiology of male genitourinary cancers

Abstract

Endocrine disrupting chemicals disrupt normal physiological function of endogenous hormones, their receptors, and signaling pathways of the endocrine system. Most endocrine disrupting chemicals exhibit estrogen/androgen agonistic and antagonistic activities that impinge upon hormone receptors and related pathways. Humans are exposed to endocrine disrupting chemicals through food, water and air, affecting the synthesis, release, transport, metabolism, binding, function and elimination of naturally occurring hormones. The urogenital organs function as sources of steroid hormones, are targeted end organs, and participate within systemic feedback loops within the endocrine system. The effects of endocrine disruptors can ultimately alter cellular homeostasis leading to a broad range of health effects, including malignancy. Human cancer is characterized by uncontrolled cell proliferation, mechanisms opposing cell-death, development of immortality, induction of angiogenesis, and promotion of invasion/metastasis. While hormonal malignancies of the male genitourinary organs are the second most common types of cancer, the molecular effects of endocrine disrupting chemicals in hormone-driven cancers has yet to be fully explored. In this commentary, we examine the molecular evidence for the involvement of endocrine disrupting chemicals in the genesis and progression of hormone-driven cancers in the prostate, testes, and bladder. We also report on challenges that have to be overcome to drive our understanding of these chemicals and explore the potential avenues of discovery that could ultimately allow the development of tools to prevent cancer in populations where exposure is inevitable.

Keywords: Environmental endocrine disruptors; Etiology; Male genitourinary cancers; Molecular mechanisms.