Genistein: Does It Prevent or Promote Breast Cancer?
Bouker, Kerrie B., Hilakivi-Clarke, Leena, Environmental Health Perspectives
Diet is estimated to contribute to approximately 50% of all newly diagnosed breast cancers. As such, a search for dietary factors differentially consumed among populations with increased breast cancer risk (e.g., Caucasians) compared to those with low risk (e.g., Asians) has become a priority. One such dietary component, which is typical to the Asian but not the Caucasian diet, is soy. We review data relevant to attempts to determine whether soy, and more specifically genistein, is a dietary component that may help to explain the dramatic disparity in breast cancer risk among these populations. Key words: antiproliferative effects, breast cancer, estrogenic effects, genistein. Environ Health Perspect 108:701-708 (2000). [Online 23 June 2000]
Epidemiologic data indicate a great disparity between breast cancer risks in Western and Eastern countries. Historically, the risk of American women developing breast cancer has been as high as 7 times that of Asian women (1). Today the disparity in risk is similarly significant, although the difference in incidence between Western and Eastern countries has narrowed slightly. For example, one in eight white women in the United States can expect to develop breast cancer in her lifetime; this risk is roughly 5-fold less in Japanese and Chinese women residing in Asia (2). However, extensive migration studies indicate that Asian women who immigrate to the United States and adopt a Western lifestyle develop risk comparable to Caucasian women within two generations (3,4). These studies provide strong evidence in support of other epidemiologic studies showing that 5-10% of breast cancer cases are estimated to be attributable to inherited factors, and thus [is greater than] 90% of newly diagnosed breast cancers may be caused by unspecified factors probably related to lifestyle. Ziegler et al. (5) investigated the link between age of immigration to the United States and increased breast cancer risk in Chinese, Japanese, and Filipino women. The authors found a strong correlation between early age of immigration ([is less than] 35 years of age) and a marked increase in breast cancer risk (5). In fact, Asian women born in America, compared to their counterparts born in the East, had a 60% higher risk of breast cancer. Additionally, in all three ethnic groups, immigrants living in the United States for more than a decade had a significantly greater risk than more recent immigrants (5).
It is clear from both epidemiologic and clinical data that exposure to estrogens has significant influences on breast cancer development. Estrogens induce the proliferation of normal and malignant mammary cells, and are thus linked to breast cancer promotion and progression. Interestingly, a number of reports indicate that Asian women living in Asia have up to roughly 40% lower serum estrogen levels than Caucasian women living in the United States or Britain (6,7). Based on these data, it is increasingly clear that the protective effect seen in Asian countries does not correlate with genetic influences, but rather, with environmental and lifestyle factors. Thus, it has long been the goal of innumerable scientists to isolate those factors that may be responsible for the dramatic disparity in breast cancer risk between Caucasian and Asian women.
Diet is estimated to contribute to up to 50% of all newly diagnosed breast cancer cases (8,9). One particular class of dietary compounds that has received much attention, based on their high concentration in potentially protective foods and their reported antiproliferative effects, is phytoestrogens. Consumption of phytoestrogens, particularly soy products, as well as legumes, is higher in Asia than in the Western world (10). Soybased diets are high in genistein (4,5,7-trihydroxyisoflavone), which has been widely studied for its potential anticancer properties. The exact mechanism by which genistein may exert its antitumorigenic effects is not clearly understood; however, it is a specific and potent inhibitor of both protein tyrosine kinases and topoisomerase II (11,12). …