Soybean Isoflavones and Cancer Risk Soybean Phytoestrogen Intake and Cancer Risk12 C. HERMAN, T. ADLERCREÃoeTZ,3* BARRY R. GOLDIN, SHERWOOD L. GORBACH, KRISTER A. V. HÖCKERSTEDT,** SHAW WATANABE, ESA K. HÄMÄLÄINEN,*** M. HELENE MARKKANEN,* TARÃoeH. MÄKELÄ,KRISTIINA T. WÄHÄLÄ, TAPIO A. HASE AND THEODORE FO7S/S**** *Department of Clinical Chemistry (Fliï-00290),**IVSurgical Department, Helsinki (Jniuersity Central Hospital (FIN-00130), and Department of Chemistry (FIN-00100), University of Helsinki, Helsinki, Finland; Department of Community Health, Nutrition/Infection Unit, Tufts University School of Medicine, Boston, MA 02] 11; Epidemiology Division, National Cancer Center Research Institute, Tsukiji 5-chome, Chuo-ku, Tokyo, Japan; ***Department of Clinical Chemistry, University Central Hospital, FIN-70211 Kuopio, Finland; ****Department of Oncology and Immunology, Children's University Hospital, Ruprecht-Karls-Universitat, D-6900 Heidelberg, Germany ABSTRACT Because many Western diseases are hor mone-dependent cancers, we have postulated that the Western diet, compared with a vegetarian or semi- vegetarian diet, may alter hormone production, metab olism or action at the cellular level. Recently, our in terest has been focused on the cancer-protective role of some hormone-like diphenolic phytoestrogens of di etary origin, the lignans and isoflavonoids. The precur sors of the biologically active compounds originate in soybean products (mainly isoflavonoids but also lig nans), as well as whole grain cereals, seeds, probably berries and nuts (mainly lignans). The plant lignan and isoflavonoid glycosides are converted by intestinal bac teria to hormone-like compounds with weak estrogenic and antioxidative activity; they have now been shown to influence not only sex hormone metabolism and bio logical activity but also intracellular enzymes, protein synthesis, growth factor action, malignant cell prolif eration, differentiation and angiogenesis, making them strong candidates for a role as natural cancer protective compounds. Epidemiológica! investigations support this hypothesis, because the highest levels of these compounds are found in countries or regions with low cancer incidence. This report is a review of results that suggest that the diphenolic isoflavonoids and lignans are natural cancer-protective compounds. J. Nutr. 125: 757S-770S, 1995. INDEXING KEY WORDS: •soybean •phytoestrogens •cancer risk Many epidemiological and migrant studies support the view that the Western diet is one of the main fac tors causing the high incidence of the so-called West ern diseases (Rose et al. 1986, Trowell and Burkitt 0022-3166/95 S3.00 ©1995 American Institute of Nutrition. 1981), including the major hormone-dependent can cers, colon cancer and coronary heart disease. Because of the fact that these diseases are related to some extent to sex hormones or sex hormone metabolism (Adler- creutz et al. 1982, Adlercreutz 1984, 1990), we have postulated that the Western diet, compared with the vegetarian or semivegetarian diet in developing and Asian countries, may alter hormone production, me tabolism or action at the cellular level by some bio chemical mechanisms. Recently, our interest has been focused on the biological role of two groups of hor mone-like diphenolic phytoestrogens of dietary origin, the lignans and isoflavonoids. These compounds, which mainly occur in soybean and whole-grain prod ucts and various seeds, have now been shown to in fluence not only sex hormone metabolism and biolog ical activity but also intracellular enzymes, protein synthesis, growth factor action, malignant cell prolif- 1 Presented at the First International Symposium on the Role of Soy in Preventing and Treating Chronic Disease, held in Mesa, AZ, February 20-23, 1994. The symposium was sponsored by Protein Technologies International, the soybean growers from Nebraska, Indiana and Iowa and the United Soybean Board. Guest editors for this symposium were Mark Messina, 1543 Lincoln Street, Port Townsend, WA 98368, and John W. Erdman, Jr., Division of Nu tritional Sciences, University of Illinois, Urbana, IL 61801-3852. 2 Supported mainly by the Medical Research Council of the Academy of Finland and the Sigrid JuséliusFoundation, Helsinki, Finland, and recent methodological and in vitro metabolic studies also by National Institutes of Health (grant no. l ROI CA56289- 01). Recent studies in Japan were supported by the Comprehensive 10-year Strategy for Cancer Control, Ministry of Health and Welfare, Tokyo, Japan. 3 To whom correspondence should be addressed: Department of Clinical Chemistry, University of Helsinki, Meilahti Hospital, FIN- 00290 Helsinki, Finland. 757S by guest on January 6, 2012 jn.nutrition.org Downloaded from