The Role of Cadmium and Nickel in Estrogen Receptor Signaling and Breast Cancer: Metalloestrogens or Not?

Abstract

During the last half-century, incidences of breast cancer have increased globally. Various factors—genetic and environmental— have been implicated in the initiation and progression of this disease. One potential environmental risk factor that has not received a lot of attention is the exposure to heavy metals. While several mechanisms have been put forth describing how high concentrations of heavy metals play a role in carcinogenesis, it is unclear whether chronic, low-level exposure to certain heavy metals (i.e. cadmium and nickel), can directly result in the development and progression of cancer. Cadmium and nickel have been hypothesized to play a role in breast cancer development by acting as metalloestrogens— metals that bind to estrogen receptors and mimic the actions of estrogen. Since the lifetime exposure to estrogen is a well-established risk factor for breast cancer, anything that mimics its activity will likely contribute to the etiology of the disease. However, heavy metals, depending on their concentration, are capable of binding to a variety of proteins and may exert their toxicities by disrupting multiple cellular functions, complicating the analysis of whether heavy metal-induced carcinogenesis is mediated by the estrogen receptor. The purpose of this review is to discuss the various epidemiological, in vivo, and in vitro studies that show a link between the heavy metals, cadmium and nickel, and breast cancer development. We will particularly focus on the studies that test whether or not these two metals act as metalloestrogens in order to assess the strength of the data supporting this hypothesis.

Efficient Removal of Cadmium Using Edible Fungus and Its Quantitative Fluorimetric Estimation Using (Z)-2-(4H-1,2,4-Triazol-4-yl)iminomethylphenol

“…1,2 Among these, endocrine disrupting effects 3−5 by heavy metals sometimes mimic estrogen and alter its activity. 6 Some evidence has shown that cadmium can cause endocrine disruption and early maturation. 7 There are several types of methods to remove heavy metals mechanically, 8−14 but the main problem is either these techniques are expensive or, to some extent, not sufficiently effective.…”

A Review on Thiazolidinediones and Bladder Cancer in Human Studies

“…Humans can be exposed to environmental and anthropogenic carcinogens [12][13][14][15][16][17][18][19][20][21][22], and diabetic patients may have a higher risk for a variety of cancers [23][24][25][26][27][28][29][30][31][32][33][34]. Diabetes is increasing in prevalence and incidence and affects hundreds of millions of people worldwide [35][36][37].…”

Association of lifestyle and demographic factors with estrogenic and glucocorticogenic activity in Mexican American women

“…isoflavones) and endogenous compounds (e.g. 27-hydroxycholesterol and estrogen metabolites) (27)(28)(29)(30)(31)(32).…”