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Cancer Epidemiology Biomarkers & Prevention Vol. 13, 1156-1162, July 2004
© 2004 American Association for Cancer Research

Mammographic Density in Relation to Daidzein-Metabolizing Phenotypes in Overweight, Postmenopausal Women

Cara L. Frankenfeld1,3, Anne McTiernan1,3,4, Erin J. Aiello1,6, Wendy K. Thomas1, Kristin LaCroix1, Judy Schramm1, Stephen M. Schwartz3,2, Victoria L. Holt3,2 and Johanna W. Lampe1,3,5

1 Cancer Prevention Program, 2 Epidemiology Program, Fred Hutchinson Cancer Research Center, Seattle, Washington; Departments of 3 Epidemiology and 4 Medicine, 5 Interdisciplinary Program in Nutritional Sciences, University of Washington, Seattle, Washington; and 6 Group Health Cooperative, Seattle, Washington

Requests for reprints: Johanna W. Lampe, Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue N. MP-900, Box 19024, Seattle, WA 98109. Phone: (206) 667-6580; Fax: (206) 667-7850. E-mail: jlampe{at}fhcrc.org

Circulating hormones are associated with mammographic density, an intermediate marker of breast cancer risk. Differences in circulating hormones, including estrone and testosterone, have been observed in premenopausal women based on their capacity to metabolize daidzein, an isoflavone found predominantly in soybeans. Equol and O-desmethylangolensin (O-DMA) are products of intestinal bacterial metabolism of daidzein. There is interindividual variability in the capacity to produce daidzein metabolites; individuals can be equol producers or non-producers and O-DMA producers or non-producers. We tested the hypothesis that daidzein-metabolizing phenotypes are associated with mammographic density. Participants were recruited from among 92 sedentary, postmenopausal women, ages 50 to 75 years, who participated in a 1-year physical activity intervention. Pre-intervention mammographic density was determined using a computer-assisted, gray-scale thresholding technique. Fifty-five of these women consumed supplemental soy protein (>10 mg daidzein/d) for 3 days and collected a first-void urine sample on the fourth day to determine daidzein-metabolizing phenotypes. Equol and O-DMA concentrations were measured using gas chromatography-mass spectrometry. Associations between daidzein-metabolizing phenotypes and percent mammographic density were adjusted for age, maximum adult weight, gravidity, family history of breast cancer, and serum follicle-stimulating hormone and free testosterone concentrations. Mammographic density was 39% lower in equol producers compared with non-producers (P = 0.04). O-DMA producers had mammographic density 69% greater than non-producers (P = 0.05). These results suggest that particular intestinal bacterial profiles are associated with postmenopausal mammographic density, and these associations are not entirely explained by differences in reproductive or anthropometric characteristics or circulating hormones.




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