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Soy and Breast Cancer: Carcinogen or Prevention?
In recent years, soy has become an important constituent in the diet of the Western world, especially among vegetarians and through use in infant formulas. The media and government have been preaching the benefits of consuming soy protein, and many “everyday” foods have been fortified with soy proteins in an effort to promote soy consumption (http://www.solaeliving.com/ ). The FDA claimed in October of 1999 that “diets low in saturated fat and cholesterol that include 25 grams of soy protein a day may reduce the risk of heart disease” (http://www.fda.gov/fdac/features/2000/300_soy.html#health). One of the most important benefits of soy being readily promoted is that the phytoestrogens in soy may be able to help prevent breast cancer. In countries that consume large amounts of soy, such as Japan, the incidence of breast cancer is markedly lower than that of Western countries, and this observation has spurred much anti-cancer research.
Of course, there are voices everywhere who claim that the aforementioned benefits of soy are nothing but propaganda, that the soy industry is not only lying about the proposed benefits but is covering up all of the negative effects soy can have on one’s health (http://www.healingcrow.com/soy/soy.html). Along with “extreme emotional behavior, depression, asthma, immune system problems, pituitary insufficiency, thyroid disorders, and irritable bowel syndrome,” Sally Fallon and Mary G. Enig, PhD, claim that there is evidence that soy protein is actually carcinogenic (http://www.westonaprice.org/soy/darkside.html). “Soy proponents don’t want the public to know that phytoestrogens can induce tumors in several different species of animals” (http://www.mercola.com/2001/apr/7/soy.htm). Fallon and Enig also cited a study published by in Cancer Research which found that genistein, a soy isoflavone, “was more carcinogenic than the synthetic estrogen DES when exposure occurred during ‘critical periods of differentiation,’ such as during infancy” (http://www.westonaprice.org/soy/darkside.html). This claim stems from the fact that soy isoflavones are estrogen-like compounds. It is generally agreed upon in the medical community that increased lifelong exposure to estrogen or elevated estrogen levels put women at a higher risk for breast cancer. Since isoflavones (or phytoestrogens) exhibit estrogen-like activity, it is possible that they could augment the effects of the body’s own estrogen and promote the development of breast cancer. Proponents of soy argue that since isoflavones are a much weaker form of estrogen than estradiol (one of the main forms of estrogen produced by the body), they might actually act as anti-estrogens and block the effects of estradiol and, thus, help prevent breast cancer (http://www.vegetarian-nutrition.info/vn/soy_breast_cancer.php).
A Look at the Biochemistry of It All
The estrogen-like behavior of soy isoflavones is a direct result of similarity in the chemical structures of the compounds.
Soy Isoflavone (Genistein)
Estradiol plays an active role in the development of the mammary glands and the uterus. As previously mentioned, excess estradiol in the body can lead to the development of estrogen-dependent tumors, specifically breast and uterine cancers (Vaya and Tamir 2004). There are two types of estrogen receptors in the body, alpha and beta receptors. Because the chemical structures are similar, the genistein compound can bind to estrogen receptors (Staar, et al 2005). Isoflavones bind more easily to beta receptors. There are two types of cancer cells that may develop in the breasts/mammary glands, estrogen receptor positive cancer cells and estrogen receptor negative cancer cells, and these cells can be activated or inactivated by estrogen or estrogen-like compounds, such as genistein (http://www.vegetarian-nutrition.info/vn/soy_breast_cancer.php). The main question to consider in soy protein cancer research is whether isoflavones act as agonists (and activate) or antagonists (and deactivate) at the estrogen receptor site.
Let’s Get Empirical!
Countless studies on the effects of soy isoflavones on breast cancer risk in humans and animals have been done in recent years.
In 2001, Dai, et al, assessed the soy consumption of Chinese women in Shanghai by using a food frequency questionnaire. A statistically non-significant decrease in breast cancer risk was observed for women who reported consuming soy at least once a week. The results suggested that regular consumption of soy may reduce the risk of breast cancer (Dai, et al 2001).
Thomas Badger conducted a meta-analysis of studies associating cancer risk with soy protein isolate consumption in rats. Mammary tumors were induced in rats that were fed exclusively soy protein isolate or exclusively casein, a protein which exerts no estrogenic activity. The results suggested that there is a significant inverse relationship between soy consumption and breast cancer risk. Also, Badger reported that “undifferentiated epithelial cells of the mammary gland” are the locations at which breast cancer develops. As a female develops, the terminal end buds of the cells differentiate into lobules, and cancer risk drops, since the number of terminal end bulbs available to develop. It was found that soy protein isolate “reduced the number of terminal end buds,” which suggests that soy protein isolate causes mammary gland development that can reduce breast cancer risk (Badger 2005).
Lin, et al, studied the effect of genistein on cell proliferation in rat breast cancer cells. The experiment suggested that “soy isoflavones activate the cAMP/PKA pathway in … rat breast cancer cells by inhibiting the activity of phospodiesterase, which induces cell arrest at the S phase of cell cycle and exerts anti-proliferative effects (Lin, et al 2005).
Anna Wu, PhD, reported that in a 1995 study funded by the California Breast Cancer Research Program, it was found, through blood tests and interviews, that a “high intake of soy foods is associated with a 30% reduction in risk of breast cancer” for Asian-American females (http://cbcrp.org/research/PageGrant.asp?grant_id=1582).
In an additional study, researchers assessed the diets of over 1,000 Asian-American women living in California between 1995 and 1998 by in-depth interviews covering soy consumption over lifetime, reproductive history, and where they had lived. They found that:
In a review of many epidemiological studies, Wietrzyk, et al, stated that, “with our current state of knowledge, we cannot conclude whether consumption of soy, SIF (soy isoflavones)-supplemented food or the use of particular isoflavones as therapeutics will have positive, null, or even adverse effects on cancer (particularly, steroid hormone-dependent) risk and treatment” (Wietrzyk, et al 2005).
In a follow-up of the Shanghai Breast Cancer Study, Boyapati, et al, assessed usual soy intake using a food frequency questionnaire of women who had previously participated in the Shanghai Study and who were survivors of breast cancer. The average follow-up time was 5.2 years, and the conclusion was that “soy intake prior to cancer diagnosis was unrelated to disease-free breast cancer survival” (Boyapati, et al 2005).
In a study of “3,000 African-American, Hispanic, and Caucasian women, aged 35 to 79” (1,300 of which had been diagnosed with breast cancer), questionnaires were used to assess the amount of soy consumed over a number of years. The researchers found no link between the amount of soy consumed and breast cancer risk (http://www.breastcancer.org/research_diet_090001a.html).
Staar, et al, isolated endometrial cells from “regularly menstruating women undergoing gynaecological abrasion or hysterectomy” and stimulated them with genistein. The binding at alpha and beta estrogen receptors was analyzed, and it was found that “endometrial glandular cells responded to stimulation with genistein…by alteration of both [alpha receptor] and [beta receptor] mRNA expression.” It was concluded that the results were “in line with findings that phytoestrogens act as anti-estrogens in organs expressing more [alpha receptor] and as estrogens in [beta receptor] presenting organs” (Staar, et al 2005).
Problems with Studies
Although most studies that were examined found that there was an inverse relationship between the amount of soy consumed and breast cancer risk, there were several problems with the studies.
First of all, the form of soy used in the experiments was inconsistent. In most animal studies, isolated soy compounds were used, while in human studies, whole soy food intake was examined. This makes it very difficult to ascertain the relevance of the animal studies to humans because different components of soy isoflavones might act in different ways upon estrogen receptors. Besides that inconsistency, animal and human estrogen receptors might react to the same isoflavone differently.
Second of all, in the studies involving humans, self-report was used to determine the amount of soy consumed. These self-report questionnaires probably lacked reliability because it is very difficult to remember/estimate how much soy one has consumed in previous years.
There might also have been confounding variables with the studies with human subjects. Perhaps people who consume more soy lead a healthier lifestyle. They might exercise more, consume more fruits and vegetables, and be more concerned with their physical well-being than people who do not consume soy. It is possible that any or all of these factors could contribute to a lower risk of breast cancer.
The evidence presented by the studies cited showed a link between soy consumption and decreased breast cancer risk, but because of the possible problems with the studies, I believe they are inconclusive at present. The soy controversy will be difficult to resolve without human experimentation with more controls for external variables, and it is very likely that most plausible experimental designs would be unethical.
As a vegetarian and a long-time consumer of soy, I have a personal testimony that my own consumption of soy has never caused health problems. In the short-term, I have noted my energy levels increase substantially since I replaced meat and dairy with soy products and have noticed many other physical benefits. My soy consumption has consisted of whole soy products, however, not isolates or soy powder additives. As far as long-term benefits to my current diet and my risk for breast cancer are concerned, only time will tell what kind of outcomes will occur.
With most of the evidence pointing toward reduced cancer risk or no effect at all and because of my personal bias, I will continue to enjoy soy on a day-to-day basis with the hope that more conclusive evidence for the positive effects of soy on breast cancer risk will soon be empirically proven.
Badger, T. M., et al. (2005). Soy protein isolate and protection against cancer. Journal of the American College of Nutrition. 24, 146-149.
Boyapati, S. M., et al. (2005). Soyfood intake and breast cancer survival: a followup of the Shanghai Breast Cancer Study. Breast Cancer Research Treatment. 92, 11-17.
Dai, Q., et al. (2001). Population-based case-control study of soyfood intake and breast cancer risk in Shanghai. British Journal of Cancer. 85, 372-378.
Lin, C. Z., et al. (2005). Effect of soy isoflavones on cAMP/PKA pathway in breast cancer cells of the rat. Sheng Li Xue Bao. 57, 517-522.
Staar, S., et al. (2005). Stimulation of endometrial glandular cells with genistein and daidzein and their effects on ERalpha- and ERbeta-mRNA and protein expression. Anticancer Research. 25, 1713-1718.
Vaya, J. & Tamir, S. (2004). The relation between the chemical structure of flavonoids and their estrogen-like activities. Current Medicinal Chemistry. 11, 1333-1343.
Wietrzyk, J., et al. (2005). Phytoestrogens in cancer prevention and therapy - mechanisms of their biological activity. Anticancer Research. 25, 2357-2366.
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