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|Date: December 31, 2004||HC# 090341-271|
Re: The Role of Phytoestrogens in Breast and Prostate Cancer
Magee P, Rowland I. Phyto-oestrogens, their mechanism of action: current evidence for a role in breast and prostate cancer. British Journal of Nutrition. 2004;91:513-531.
Phytoestrogens are hormone-like compounds, structurally similar to the female hormone estrogen, that occur naturally in some plant foods. The authors, from the University of Ulster in the United Kingdom, review the effects of phytoestrogens on breast and prostate cancer in vivo and in vitro and discuss the compounds' possible mechanisms of action. They point out that plasma and urinary levels of phytoestrogens are much higher in areas where cancer incidence is low compared with areas of high cancer incidence. The two main classes of phytoestrogens are the isoflavones, found predominantly in soy beans, and the lignans, found in foods such as flaxseed, cereals, fruits, and berries.
As the authors note, diet is thought to play a major role in cancer risk. The incidence of breast cancer is much higher in Western populations compared with Asian populations, whose diets are traditionally low-fat, high-fiber, high-soy diets. In addition, Asian women living in Asia have approximately 40% lower serum estrogen levels than Caucasian women living in the United States or Britain.1,2
Results from studies investigating the effects of phytoestrogens on breast cancer risk have been conflicting. For example, high intakes of soy proteins and total soy products were associated with a decreased risk of breast cancer in premenopausal Singapore Chinese women in a case-control study.3 On the other hand, a case-control study in two Chinese populations found no protective effect against breast cancer with a high intake of soy protein.4
Most animal studies have shown that the phytoestrogens can protect against chemically induced mammary cancer and that the time of exposure to the test compound is important. Rats treated with genistein (one of the isoflavones, both neonatal and in prepuberty) have a longer latency before the appearance of chemically induced mammary tumors and a marked reduction in tumor number, whereas rats treated after 35 days of age have smaller alterations in breast cancer risk.5 This suggests that early exposure to soy bean products is important in breast cancer prevention and may explain why protection against breast cancer is lost in Asian immigrants after a few generations.
Both epidemiological and in vivo studies have demonstrated a protective role of phytoestrogens against breast cancer; however, say the authors, "their precise mechanisms of action remain to be shown and can only be determined at the cellular level by in vitro studies."
Prostate cancer mortality is higher in the West, although the incidence of latent and noninfiltrative forms of the disease is similar in the Western world compared with Asian populations, explain the authors. As with breast cancer, environmental factors, especially diet, have been implicated in the risk for prostate cancer. Other risk factors include age, race, polymorphic repeats in the androgen receptor gene,6 and high circulating levels of androgens and insulin-like growth factor.7
Isoflavonoid levels have been found to be higher in men living in Eastern countries, where prostate cancer mortality is low, compared with those living in the West; e.g., plasma isoflavonoid levels in Japanese men have been shown to be 7 to 110 times higher than those of Finnish men.8 The authors cite several studies showing the consumption of soy products associated with a decreased risk of prostate cancer. Few human studies, they say, have investigated the specific effects of phytoestrogens on prostate cancer risk and although isoflavone and lignan intake would appear to protect against prostate cancer, a firm link remains to be established.
Studies in animal models of prostate cancer have demonstrated a protective effect of phyotestrogens against the development of prostate cancer.
In vitro studies have shown that both isoflavones and lignans inhibit the growth of prostate cancer cell lines. However, except for one study, the concentration required for growth inhibition exceeds that which would be achieved from dietary intake. Most studies have reported the growth inhibition of prostate cancer cells by phytoestrogens to be dose dependent.
Many of the mechanisms of action postulated for the role of phytoestrogens in prostate cancer are shared with those of breast cancer.
The authors conclude that phytoestrogens do not appear to act through a single mechanism of action. Structurally related phytoestrogens have discrete target sites and mechanisms of action in inhibiting the growth of cancer cells, and phytoestrogens with similar structures may not produce an identical biological response.
"It is extremely difficult to draw any definite conclusions as to the effects of phyto-oestrogens on breast and prostate cancer risk," say the authors. "Clearly more research is needed before a definite conclusion concerning the chemoprotective properties of phyto-oestrogens can be drawn."
1Goldin B, Adlercreutz H, Gorbach S, et al. The relationship between estrogen levels and diets of Caucasian American and Oriental immigrant women. Am J Clin Nutr. 1986;44:945-953.
2Key T, Chen J, Pike M, Boreham J. Sex hormones in women in rural China and Britain. Br J Cancer. 1990;62:631-636.
3Lee H, Gourley L, Duffy S, Esteve J, Lee J, Day N. Dietary effects on breast-cancer risk in Singapore. Lancet. 1991;337:1197-1200.
4Yuan JM, Wang QS, Ross RK, Henderson BE, Yu MC. Diet and risk of breast cancer in Shanghai and Tianjin, China. Br J Cancer. 1995;71:1353-1358.
5Barnes S, Grubbs C, Setchell KDR, Carlson J. Soybeans inhibit mammary tumours in models of breast cancer. In: Pariza M, Aeschbacher H, Felton J, Sato S (eds). Mutagens and Carcinogens in the Diet. New York, NY: Wiley-Liss; 1990:239-253.
6Stanford JL, Just JJ, Gibbs M, et al. Polymorphic repeats in the androgen receptor gene: molecular markers of prostate cancer risk. Cancer Res. 1997;57:1194-1198.
7Signorello LB, Brismar K, Bergstrom R, et al. Insulin-like growth factor-binding protein-1 and prostate cancer. J Natl Cancer Inst. 1999;91:1965-1967.
8Adlercreutz H, Markkanen H, Watanabe S. Plasma concentrations of phyto-oestrogens in Japanese men. Lancet. 1993;342:1209-1210.