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Dietary estrogens and human breast cancer

Dietary estrogens stimulate human breast cells to enter the cell cycle.

Dees C, Foster JS, Ahamed S, Wimalasena J. Environ Health Perspect 1997 Apr 105 Suppl 3 633-6

Abstract

It has been suggested that dietary estrogens neutralize the effect of synthetic chemicals that mimic the effects of estrogen (i.e., xenoestrogens, environmental estrogens).

Genistein, a dietary estrogen, inhibits the growth of breast cancer cells at high doses but additional studies have suggested that at low doses, genistein stimulates proliferation of breast cancer cells. Therefore, if dietary estrogens are estrogenic at low doses, one would predict that they stimulate estrogen-receptor positive breast cancer cells to enter the cell cycle.

Genistein and the fungal toxin zearalenone were found to increase the activity of cyclin dependent kinase 2 (Cdk2) and cyclin D1 synthesis and stimulate the hyperphosphorylation of the retinoblastoma susceptibility gene product pRb105 in MCF-7 cells. The steroidal antiestrogen ICI 182,780 suppressed dietary estrogen-mediated activation of Cdk2.

Dietary estrogens not only failed to suppress DDT-induced Cdk2 activity, but were found to slightly increase enzyme activity.

Both zearalenone and genistein were found to stimulate the expression of a luciferase reporter gene under the control of an estrogen response element in MVLN cells.

Our findings are consistent with a conclusion that dietary estrogens at low concentrations do not act as antiestrogens, but act like DDT and estradiol to stimulate human breast cancer cells to enter the cell cycle.

Xenoestrogens significantly enhance risk for breast cancer during growth and adolescence.

Ardies CM and Dees C. Med Hypotheses 1998 Jun 50:6 457-64

Abstract

Breast cancer is one of the most common forms of cancer observed in women, and endogenous estrogen is thought to play a major role in its development. Because of this, any conditions or exposures which enhance estrogenic responses would result in an increased risk for breast cancer.

The role of xenoestrogenic compounds, such as DDT, in the etiology of breast cancer is still very controversial.

In the following paper we discuss recently-published observations by ourselves and others which indicate that xenoestrogens may play a significant role in the development of breast cancer. Specifically, we hypothesize that during periods of high growth rates and during breast development the sensitivity of breast cells to estrogenic compounds is sufficiently great for xenoestrogens to significantly enhance risk for breast cancer.

Author Address

Health Sciences Research Division, Oak Ridge National Laboratory, Tennessee, USA.