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Phytonutrients in cancer

Nutrition is among the factors associated with cancer, both in a protective and promotive manner. Throughout the past 50 years, correlations between dietary patterns and cancer incidence have been identified through studies of human populations. The emerging conclusion is that a reduced cancer risk is associated with diets high in plant foods when compared to Western diets composed primarily of animal foods.

Plant- and animal-based diets differ nutritionally where cancer risk is concerned. Factors include differences in concentrations of fiber, antioxidant vitamins and minerals, fat type and amount, and total calories.

In the past 10 years, researchers have identified other compounds in plant foods that also may affect cancer risk. These are broadly identified as phytonutrients compounds found in plants that produce a biological response or mimic mammalian hormones. Researchers now are faced with the daunting task of studying the vast number of potential compounds found in plant foods in order to find those that may have cancer-prevention properties.

Phytoestrogens
One group of compounds garnering much research attention is phytoestrogens, which are found in high concentrations in soy and red clover. Because these compounds mimic the human hormone estrogen, they potentially can influence cancers that are affected by estrogen. Soy phytoestrogens, primarily genistein and daidzein, recently have gained attention as natural replacements for estrogen in reducing menopausal symp-toms. These phytoestrogens can be purchased as over-the-counter nutritional supplements.

Estrogen
Estrogen appears to significantly affect the development of breast, colon and prostate cancer. In collaboration with Dennis Lubahn, PhD, associate professor of biochemistry and child health molecular biology at the University of Missouri, Columbia, we have used estrogen receptor a knockout (ERaKO) mice to study the role of estrogen and phytoestrogens in cancer development. ERaKO mice lack one of the major types of estrogen receptors Ñ alpha Ñ but have a normal expression of the beta form. The absence of ERa in these mice is advantageous for distinguishing which estrogen receptor form is involved in breast cancer and influenced by genistein.

In our study, female ERaKO and normal mice were provided with a diet containing either 0 or 1 gram of genistein per kilogram. This level of genistein was higher than would be obtainable by eating soy but could be consumed from supplements. Breast tumors were induced in the mice using the carcinogen DMBA. After 13 months, none of the ERaKO mice and 75 percent of the normal mice developed tumors. Hence, in the absence of ERa, DMBA did not generate breast tumors, likely as a result of the failure of the ERaKO mice to produce mature mammary tissue.

In the normal mice, genistein increased the number of poorly differentiated tumors, which is an indication of a more progressive stage of cancer. This observation suggests that genistein may act like estrogen as a promoter of breast cancer and raises significant questions about the administration of genistein to women who may be at risk for developing the disease.

Colon cancer
In another MU study, male ERaKO and normal mice were provided with diets containing 0 or 1 gram of genistein per kilogram. Colon tumors were induced with the carcinogen AOM. At the end of the study, more of the ERaKO mice had colon tumors than normal mice, which suggests the estrogen receptor is protective of colon cancer.

Genistein affected colon-tumor formation in the two animal models in opposite ways. More tumors were observed in genistein-fed normal mice, whereas ERaKO mice had fewer tumors when fed genistein. Because the number of animals in this study was small, we cannot make strong conclusions from these results.

Studies performed at Michigan State University in East Lansing suggest that patients at high risk for developing colon cancer have improved colonic-cell parameters following consumption of soy protein for one year. Therefore, the possible benefit of soy in reducing colon cancer risk is suggested but not fully defined.

Conclusion
The role of phytoestrogens in cancer prevention appears to be complex. It is essential to understand fully the role these and other compounds play in cancer risk because they increasingly are being used by consumers in pure form. A significant difference may exist between consuming soy phytoestrogens at the levels and in combinations naturally found in soy foods and in consuming large amounts of concentrated compounds. Hence, studies are needed to determine the effects of these compounds on cancer development so their efficacy and risks can be known.