Cruciferous Vegetables and Human Breast Cancer: An Important Interdisciplinary Hypothesis in the Field of Diet and Cancer - Statistical Data Included

Family Economics and Nutrition Review, Fall, 1999 by Ron Jevning, Mark Biedebach, Rajen Anand

At the same time, strong biochemical evidence links estrogen to cancer of reproductive tissue. Estrogen activates the parts of the chromosome (DNA) that promotes cell division. We know, however, that more than one form of estrogen exists: estradiol, the form normally secreted, promotes cell division in a well-controlled manner, while 16-hydroxyestrone (C-16), another form of estrogen, seems to promote cell division in an uncontrolled manner that can lead to cancer in affected tissue (23).

C-16 is one of the metabolites of normal estrogen, from which it differs only by the presence of a hydroxyl group on the number 16 carbon atom; C-2, the alternative estrogen metabolite, is a "safe" (inactive) substance.

Finally, we know that women with a family history of breast cancer have elevated blood C-16 (4); and the anti-estrogenic prescription drug 4-hydroxy tamoxifen (or simply tamoxifen) lowers blood C-16 and reduces both the incidence of breast cancer and the growth rate of existing breast cancer cells (13,14,21).

A Biochemically and Physiologically Based Breast Cancer-Diet Hypothesis

In the 1970's, Wattenberg reported that a diet of cruciferous (specifically brassica) vegetables[3] was associated with an anti-breast cancer effect in animals (24). Wattenberg also identified a chemical compound in the vegetables, indole-3-carbinol (i-3-C), as the main contributor to their anti-cancer effect. Later authors have reported decreased formation of C-16 associated with increased vegetable diets (5). Such findings as these and those we discussed above led Michnovicz to hypothesize that cruciferous vegetables or purified i-3-C may reduce breast cancer initiation or the C-16/C-2 ratio by decreasing C-16 in the metabolism of estrogen (19,20). While there is already some experimental support for this hypothesis (3,19), larger clinical studies of i-3-C are necessary and are in progress (20).

Importance of Breast-Diet Hypothesis

Scientifically based references such as the Food Guide Pyramid or the Dietary Guidelines for Americans, published by the U.S. Department of Agriculture, exemplify bodies of knowledge relating to dietary guidance that may change with time. Therefore, on the basis of much research (some of which we have described), we know that Americans should probably choose a diet low in fat and cholesterol and one with plenty of vegetables and grains. However, much of our knowledge lacks specificity. For example, are there particular diets that may protect against cancer?

The possible link among crucifers, estrogen, and breast cancer illustrates how change in our knowledge will probably occur. Therefore, even if the details of this hypothesis prove wrong, its epidemiological, physiological, and biochemical basis has already stimulated new research and discoveries. To exemplify this, we first note that net C-16 removal is mediated by representatives of a particular enzyme group known as "mixed function oxidases" (MFO's) (24) and that i-3-C activates these enzymes (8). MFO's have a generalized tissue function of rendering toxic substances harmless (including many otherwise carcinogenic compounds). Questions important for cancer in general then have arisen that include "what other substances than i-3-C can activate the C-16 removing MFO's? In what other tissues can general MFO activity be increased?" For example, it has been reported that ascorbigen, a vitamin-C group compound (6), activates MFO and that there is marked synergy in MFO activation by administration of both i-3-C and ascorbigen (even though ascorbigen is a nucleoside that itself contains i-3-C) (5,16,17). McDanell also reports MFO activation or a synergistic effect of joint i-3-C and ascorbigen on MFO activity in a wide variety of tissues, including small intestine, large intestine, liver, and lung (17). We can then reasonably ask this: "Are there cancer prevention or treatment implications of i-3-C or ascorbigen for tissues other than breast tissue? Is MFO activation operative in the reported anti-cancer effect of a vegetable diet on a wide variety of these tissues? Can benefits be enhanced by combination i-3-C/ ascorbigen supplementation or administration?"