Prenatal exposure to DES alter mammary cancer susceptibility

Endocrine-active chemicals in mammary cancer causation and prevention

2012 Study Abstract

Endocrine-active chemicals alter or mimic physiological hormones. These compounds are reported to originate from a wide variety of sources, and recent studies have shown widespread human exposure to several of these compounds.

Given the role of the sex steroid hormone, estradiol, in human breast cancer causation, endocrine-active chemicals which interfere with estrogen signaling constitute one potential factor contributing to the high incidence of breast cancer.

Thus, the aim of this review is to examine several common endocrine-active chemicals and their respective roles in breast cancer causation or prevention.

  • The plastic component, bisphenol A (BPA),
  • the synthetic estrogen, diethylstilbestrol (DES),
  • the by-product of organic combustion, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD),
  • the soy component, genistein,
  • and the red grape phytoalexin, resveratrol,

have some degree of structural similarities to each other and estradiol.

However, despite these structural similarities, the in vitro and in vivo properties of each of these chemicals vary greatly in terms of breast cancer causation and prevention.

Early life exposure to BPA and DES increases rodent susceptibility to chemically induced mammary carcinogenesis, presumably through retardation of normal mammary gland maturation and/or disrupting the ratio of cell proliferation and apoptosis in the mammary gland.

A recent study showed that in utero DES-exposed women greater than 40 years of age exhibited a statistically significant increase in the relative risk of developing breast cancer. This increase in risk was even more pronounced in DES-exposed women older than 50, though small samples size limited statistical significance. Also,there appears to be an increased risk of developing breast cancer associated with the mothers exposed to DES during pregnancy, though this appears to be a modest increase which does not manifest until decades after DES administration.

On the other hand, early exposures to genistein and resveratrol protect rodents against chemically induced and spontaneous mammary cancers. This is reported to occur through the ability of genistein and resveratrol to accelerate mammary gland maturation.

Interestingly, TCDD, which is the most structurally dissimilar to the above chemicals and functions as an anti-estrogen, also increases chemically induced mammary carcinogenesis through retardation of mammary gland maturation.

This article is part of a Special Issue entitled ‘Endocrine disruptors’.

Sources

  • Endocrine-active chemicals in mammary cancer causation and prevention, The Journal of steroid biochemistry and molecular biology, NCBI PubMed PMID: 21729753, 2012 Apr.
  • Featured image credit Embarazo-feliz.
DES DIETHYLSTILBESTROL RESOURCES

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