COLON CANCER AND SOY
There will be an estimated 95,600 cases of colon cancer in 1998. Incidence rates have declined in recent years from a high of 53 per 100,000 in 1985 to 44 per 100,000 in 1994. This decline has been primarily seen in whites, although incidence rates for African Americans may also be starting to decline. The recent decline may be due to increased screening and polyp removal.
There will be an estimated 47,700 deaths from colon cancer in 1998 (10% of all cancer deaths). During the past 20 years, mortality rates for colorectal cancer have fallen 25% for women and 13% for men, reflecting both decreasing incidence rates and increasing survival rates. The primary risk factors associated with colon cancer include a personal or family history of colorectal cancer or polyps, and inflammatory bowel disease. Other possible risk factors include physical inactivity, high-fat and/or low-fiber diet, as well as inadequate intake of fruits and vegetables. The National Cancer Institute estimates overall annual costs for cancer in general at $107 billion: $37 billion/direct medical costs, $11 billion/morbidity costs (cost of lost productivity), and $59 billion/mortality costs (1).
Soy products contain 5 known classes of anti-cancer agents including phytoestrogens (isoflavones, which are unique to soy), protease inhibitors, phytate, phytosterols, saponins, as well as other possible anticarcinogens such as phenolic acids, lecithin, fiber and omega-3 fatty acids (2). Although protease inhibitors have been considered antinutrients due to the fact that they interfere with digestion (even though they are heat sensitive and are mostly destroyed upon cooking), certain protease inhibitors, such as the Bowman-Birk inhibitor (BBI) and Kunitz trypsin inhibitor (KTI) found in soy, have been shown to prevent carcinogenesis in animal models and in cell cultures (3). Phytate has also been considered an antinutrient due to its ability to bind calcium and iron in the intestine, and thus inhibiting their absorption. However, it is the binding of iron (a producer of free radicals), that seems to be one of the mechanisms by which phytate may inhibit cancer (4). Phytosterols such as beta-sitosterol, are not absorbed well, moving through the intestines to the colon and have been shown to reduce the development of colon tumors (5). Saponins have been shown to be anticarcinogenic in several in vivo and in vitro studies. Proposed mechanisms include its antioxidant effect, cytotoxicity of cancer cells, and regulation of cell proliferation (6a,b).
The two primary isoflavones in soy products are genistein and diadzein which have been shown to be anticarcinogenic in several possible ways. Isoflavones are very similar in structure to estrogen and are able to bind estrogen receptors, though they exhibit only a weak estrogenic effect. Since high levels of estrogen have been linked to breast cancer and other hormone-related cancers, isoflavones may work by binding estrogen receptors and blocking the harmful effects of estrogen, thus functioning as antiestrogens. A variety of other anti-cancer mechanisms have also been proposed. Genistein has been shown to inhibit growth of both human and rodent cancer cell lines in vivo and in vitro and one proposed mechanism is through its inhibition of certain enzymes that stimulate cancer cell growth such as protein tyrosine kinases (7), though one study concluded that the mechanism of chemoprevention by genistein was independent of this (8). Genistein also induces differentiation of some malignant cells into benign cells, possibly interfering with carcinogenesis (9a,b), and inhibits angiogenesis thus reducing the blood supply to growing tumors (10). Finally, genistein also works as an antioxidant, preventing cell damage from free radicals (11)
To date, there have been eight case-control studies on the relationship of soy and colorectal cancer in China, Japan and Japanese living in the U.S. The relationship is still unclear, as studies have shown insignificant, protective or causative results in equal numbers (12). However, of the studies that found soy to be protective, two found that frequent consumption of soybeans and tofu decrease colon cancer risk (13, 14) and a third case-control study involving 488 matched pairs, age 50-74 years found that a higher consumption of tofu or soybeans was inversely associated with adenomatous colorectal polyps, which are precursors to colorectal cancer. Those consuming one or more servings of tofu or soybeans per week had half the risk of polyps compared to those not consuming soy (15).
A clinical trial is currently underway at Michigan State University to determine if soy protein can reduce the risk of colon cancer. The study involves 60 subjects consuming a supplement containing either 38g of soy protein or casein (control) for 1 year. Cell proliferation patterns, mitotic frequency and protein kinase activity are being evaluated, which are all indicators for colon carcinogenesis (16).
Some studies using animal models have shown that genistein reduces the numbers of aberrant (atypical) crypts formed (aberrant crypts are precursors of colon cancer) (17). In another animal study of precancerous lesions in the colon of rats, soy flour reduced lesions by 40% and genistein (150 ppm) reduced lesions by 35% (18). However, a third study found no significant effect (19). A study done to determine the effects of genistein and daidzein on the growth of human colon cancer cells in vitro found that growth was inhibited (20).
Although it is too early to know definitively what role soy may play in reducing colon cancer, I would encourage the consumption of soy products, as a part of a plant-based, high fiber, low fat diet which should also be high in fruits and vegetables (5-9 servings per day) to help prevent colon cancer. Regular aerobic exercise is also important.
This information is provided by:
Clare M. Hasler, Ph. D.
For more information about Dr. Hasler, see the Soy and Human Health Ask an Expert page.