Exposure to Endocrine Disrupting Chemicals and Risk of Breast Cancer

Abstract

Breast cancer (BC) is the second most common cancer and the fifth deadliest in the world. Exposure to endocrine disrupting pollutants has been suggested to contribute to the increase in disease incidence. Indeed, a growing number of researchershave investigated the effects of widely used environmental chemicals with endocrine disrupting properties on BC development in experimental (in vitro and animal models) and epidemiological studies. The complex effects of endocrine disrupting chemicals (EDCs) on hormonal pathways, involving carcinogenic effects and an increase in mammary gland susceptibility to carcinogenesis-together with the specific characteristics of the mammary gland evolving over the course of life and the multifactorial etiology of BC-make the evaluation of these compounds a complex issue. Among the many EDCs suspected of increasing the risk of BC, strong evidence has only been provided for few EDCs including diethylstilbestrol, dichlorodiphenyltrichloroethane, dioxins and bisphenol A. However, given the ubiquitous nature and massive use of EDCs, it is essential to continue to assess their long-term health effects, particularly on carcinogenesis, to eradicate the worst of them and to sensitize the population to minimize their use.

Keywords: DDT; bisphenol A; breast cancer; diethylstilbestrol; dioxin; endocrine disrupting chemicals.

Figure 1

Key Characteristics of endocrine disrupting chemicals (EDCs). (A) EDCs can modulate the synthesis of steroid hormones from cholesterol by modulating the expression of the enzymes involved in the process. (B) They may also compete with steroid hormones for binding to transport proteins, thereby modulating the free fraction of steroid hormones. (C) EDCs can bind to steroid receptors (SRs) (estrogens, androgens, aryl hydrocarbon) and act as agonists or antagonists. (D) The SRs—EDCs complex can then bind to DNA via, for example, the estrogen response element (ERE) and thus modulate the expression of the target genes. (E) In addition, EDCs can modulate the epigenetic profile of the cell (methyl mark and microRNA). (F) Finally, they can modulate the expression of enzymes involved in the catabolism of estrogens into hydrophilic compounds.