The Role of Soya in Reducing Risk of Breast and Prostate Cancer

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In 1990, the US National Cancer Institute allocated nearly $3 million to study the anti-cancer properties of soy, the large part because soyabeans are unique dietary source of isoflavones. Because of the low breast cancer mortality rates in Asia, most focus was initially on this particular cancer. More recently, the possibility that soya and isoflavones reduce prostate cancer risk has attracted attention. Isoflavones have chemical structure similar to estrogen but bind preferentially to estrogen receptor beta. However, isoflavones also have non-hormonal properties that likely contribute to their hypothesized anti-cancer effects. In vitro, the main soyabean isoflavones genistein inhibits the growth of essentially all type of cancer cells. Animal studies generally show that adding soya or isolated isoflavones to typical laboratory diets reduces mammary carcinogenesis by 25-50%. However, Asian epidemiological studies provide little support for the notion that the adult consumption of soya reduces post-menopausal breast cancer risk. This may be because migration data indicate that early life experience profoundly affecting later risk of developing breast cancer. Consistent with this observation are studies showing that rodents exposed to soya even just briefly during the prenatal and pubertal periods develop 50% fewer mammary tumors during adulthood. Similarly, recent epidemiological findings indicate Chinese women who consumed soya during the teenage years were 50% less likely to develop breast cancer as adults. The relationship between prostate cancer and soya intake as been studied to only a limited extent but the data are particularly encouraging. Isolated isoflavones and isoflavones-rich soya protein reduce chemically induced and spontaneous prostate tumor development, and inhibit tumor growth in mice implanted with prostate cancer cells. Two recently conducted epidemiological studies found that one serving of soya per day was associated a nearly 70% reduction in prostate cancer risk. Finally, isoflavones supplements were recently found to decrease prostate specific antigen levels in patients with uncontrolled prostate cancer. Overall, although still speculative , the evidence suggest that early soya consumption during adulthood may substantially reduce prostate cancer mortality.

In 1990, the US National Cancer Institute allocated nearly $3 million to study the anticancer properties of soya. At the time, most of the attention was focused on breast cancer. And while the relationship between soya and breast cancer risk continues to be a promising area of research , findings suggest that soya foods may be very important for important for preventing and even treating prostate cancer. There are multiple mechanisms by which soyabeans. However, most evidence suggest the isoflavones are responsible for the hypothesized anticancer effects of soya. In vitro, genistein, the main isoflavones in soyabeans, inhibits the growth of a wide range of cancer cells including both hormone dependent and hormone independent breast and prostate cancer cells. This short paper briefly reviews the evidence relating to the effects of soya consumption on breast and prostates cancer risk.

Breast Cancer

The low breast cancer mortality rates among soya foods consuming populations in combination with data showing that weak estrogen can function as anti-estrogens prompted initial speculation that soya might reduce breast cancer risk; this is why earlier age at menses, and later age at menopause, and hormone replacement are considered to be risk factors for breast cancer. The first animal study showing that genistein possessed anti-estrogenic activity was published in 1996. There are multiple mechanisms by which isoflavones can exert anti-estrogenic effects although there are no definitive data in humans indicating this is a case. Of course, because genistein influence several signal transduction pathways relevant to the growth of cancer cells, anti-estrogenic effects are not only means by which soya can reduce breast cancer risk.

Several studies have examined the effects of protein and isoflavones on the developments of mammary cancer in adult animals. The data are somewhat inconsistent, but generally show that the addition of soya to a standard laboratory diet typically does not significantly inhibit tumor incidence (percentage of animals the group with tumors) but in most cases, inhibits tumor multiplicity by 25-50%.

Somewhat surprisingly, given the low breast cancer mortality rates in Asian countries, Asian epidemiological studies provide little support for the notion that the adult consumption of soya reduces post-menopausal breast cancer risk, although there is some modest support for protective effects against pre-menopausal breast cancer. A few studies conducted among Western population have found soya consumption is protective. But soya intake in these studies was so minimal, that the relevance of these findings is unclear.

Early Soya Consumption

There is a particular interest in the possible protective effects of early soya consumption on adult breast cancer risk. This hypothesis is particularly intriguing because migration data indicate early life events greatly influence the development of breast cancer in adults. Lamartiniere and colleagues have consistently shown that exposing rates to genistein through the oral and intravenous route for short periods during the peri-natal periods and pre-pubertal periods reduce chemically induced mammary cancer by approximately 50%. Furthermore, Lamartiniere et al have found that in their studies, genistein inhibits mammary cancer when given to adult animals only when first given to animals when young. Recently, Badger has confirmed the findings of Lamartiniere et al using soya protein isolate. Finally, and most importantly, Shu et al found that Chinese women who consumed on average approximately 11g of soya protein per day during the teenage years were 50% less likely to develop breast cancer compared to Chinese women who rarely consumed soya during the period.

Possible Contraindications

Surprisingly, despite the low Asian breast cancer mortality rates concern has arisen that soya, because of the estrogen-like effects of isoflavones, may stimulate the growth of estrogen-receptor positive (ER+) breast tumors. For this reason, some oncologists recommend that their breast cancer patients not consume soya foods. Several observations support this dietary restriction but overall, the evidence suggests this is an unnecessary precaution.

At physiological concentrations genistein stimulates the growth of ER+ breast cancer cells where only at very high concentrations is growth inhibition observed. These biphasic effects emanate from the estrogen-like properties of genistein that become relevant at higher concentrations. However, cell systems are lacking a host of growth and transcription factors that likely influence the carcinogens process in vivo, which suggests in vitro data, may not be relevant to humans.

In contrast to the bulk of studies that in adult animals soya at least modestly inhibits mammary glands tumerogenesis, both genistein and soya protein isolate stimulate tumor growth in ovariectomized immune system deficient mice implanted with ER+ breast cancer cells. But this model has been roundly criticized on methodological grounds and in similarly designed experiments using intact not ovariectomized rodents, genistein actually inhibited, rather than stimulated, tumor growth. However, two studies in humans have promoted concerns about women with ER+ breast cancer consuming soya, as both seem to suggest that soya exerts weak estrogen like effects on breast tissue. Nevertheless, in a comprehensive review that examined all aspects of this issue, Messina and Loprinski concluded that women with breast cancer do need to need discontinue using soya products.

This review noted that observational data suggest that it is the progesterone, not the estrogen, component of hormone replacement therapy that increases breast cancer risk, and that not even HRT has been shown to adversely effect the survival of breast cancer patients. This strongly suggests isoflavones would not be harmful to breast cancer patients since isoflavones possess no progesterone activity. Furthermore, yearlong studies recently found that isoflavones supplements in pre-menopausal women had no effect on breast tissue density whereas in post-menopausal women, isoflavones decreased density. Factors that decrease breast tissue density have been shown to be protective against breast cancer.

Prostate Cancer

The International Prostate Health Council, a European expert committee, recently concluded that isoflavones were isoflavones were responsible for preventing the progression of latent prostate cancer to the more advanced forms of this disease. Thus, soya intake may help to explain why although Japanese men do develop prostate cancer they rarely die from it. In support of this contention are intriguing in vitro, rodent, and human data. In vitro, genistein inhibits the growth of hormone-dependant and independent prostate cancer cells, independent of growth effects, inhibits the metastatic potential of prostate cancer cells. Similarly, Geller et al have shown that in histoculture genistein inhibits the growth of prostate tisuue from humans with benign prostratic hyperpalsia and prostate cancer.

Animal Studies

In severe combined immune-deficient mice implanted with LNCaP human prostate cancer cells, Zhou et al found that isolated isoflavones inhibited tumor growth in a dose-dependant manner. Also Dalu et al found that genistein administration down-regulated epidermal growth factor receptor levels in the rat prostate despite rather low prostate genistein concentrations. This suggests, as noted by Zhou et al, that genistein may actually be more potent in vivo than in vitro, and therefore, than rather high genistein concentrations required to inhibit the growth of prostate cancer cells in vitro may be relevant to humans consuming soya. Findings by Zhou et at agree with those of Mentor-Mrcel et al who foundthat dietary genistein reduces the incidence of poorly differentiated prostratic adenocarcinoma in transgenic mice.

Finally, Polland et al found in several studie that isoflavones rich soya protein inhibits both spontaneously formed and chemically induced prostate cancer in Lobund-Wistar rats in comparison to soya protein low in, or nearly devoid of, isoflavones. Interestingly, based on their work in Lobund-Wistar rats, Pollanf et al concluded that isoflavones inhibit prostate cancer but that components in soya meal may inhibit their anti-carcinogenic effects.

Human Studies

The epidemiological data on soya intake and prostate cancer risk are fairly limited, but worth noting in particular are the results from two prospective epidemiological studies. In one, Japanese men in Hawaii who consumed tofu approximately once per day, were 65% less likely to develop prostate cancer in comparison to men eating tofu less than once per week. In the other study, Seventh-day Adventist men in California who consumed soya milk more than once daily were 70% less likely to develop prostate cancer as men who did not consume soya milk. The pronounced protective effects of soya consumption inthese studies is striking, but in both studie the number of men who developed prostate cancer was realatively small. Still, the observation that such modest amounts of soya could substantially resuce the risk of prostate cancer is encouraging.

Relatively, little clinical work has been conducted but Morton et al did find that isoflavones levels in prostatic fluid are higher in men from soya food consuming countries that from countries where soya is not consumed, and that isoflavones are concentrated in the prostratic fluid by about two-fold relative to the serum. Thus, the prostate gland is exposed to high concentrations of isoflavones in men who eat soya foods. Nevertheless, Urban et al failed to find that soya consumption lowered prostate specific antigen (PSA) levels in healthy men, but this was a short-term trail, which involved men with relatively low PSA levels. More importantly, and in contrast to this study, Kucak et al from the Karmanos Cancer Institute in Detroit, Michigan, recently reported that in a six month study, more than half of the 41 patients with uncontrolled cancer as determined by a rising PSA level, favorably responded to daily supplements of isoflavones.

Conclusions

Collectively, the evidence overwhelmingly supports the notion that if soya consumption redced prostate cancer risk, isoflavones are responsible for this effect. Since migration data indicate that late life events influence prostate cancer risk, this suggests that possibility that even men who are middle-aged and older who begin to consume even modest amounts of soya can reduce their likelihood of developing prostate cancer. If soya even slightly delays tumor onset and/or slows the progression of the disease, morbidity and mortality from prostrate cancer will be substantially reduced in high risk countries since prostate cancer is a disease of older men and tumors are generally slow growing. Men will die with their cancer rather than of their cancer.

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