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Phytoestrogen Exposure Is Associated with Circulating Sex Hormone Levels in Postmenopausal Women and Interact with ESR1 and NR1I2 Gene Variants

¹ Medical Research Council Dunn Human Nutrition Unit; ² Cancer Research-UK Department of Oncology, Strangeways Research Laboratory; ³ Institute of Cancer Research, London, United Kingdom; and ⁴ European Prospective Investigation of Cancer and Nutrition-Norfolk, Strangeways Research Laboratory, Cambridge, United Kingdom

Requests for reprints: Sheila A. Bingham, Medical Research Council Dunn Human Nutrition Unit, Wellcome Trust/Medical Research Council Dunn Human Nutrition Unit Building, Hills Road, Cambridge CB2 2XY, United Kingdom. Phone: 44-1223-252760; Fax: 44-1223-252765. E-mail: sab{at}mrc-dunn.cam.ac.uk

In this large cross-sectional study, we investigated the relationship between phytoestrogen exposure and circulating sex hormones and sex hormone-binding globulin (SHBG) levels in 1988 healthy postmenopausal women and their interactions with polymorphisms in genes involved in estrogen signaling. Plasma estradiol, testosterone, androstenedione, estrone, and SHBG were measured. Urinary levels of five isoflavones (daidzein, genistein, glycitein, O-desmethylangolensin, and equol) and two lignans (enterodiol and enterolactone) were measured and used as biomarkers for dietary intakes. Eighteen polymorphisms in ESR1, ESR2, and NR1I2 genes were genotyped. Results showed that lignans were positively associated with plasma SHBG levels (_p² = 1.2%; P < 0.001) and negatively associated with plasma testosterone (_p² = 0.2%; P = 0.042). Equol was negatively associated with plasma estradiol levels (_p² = 0.3%; P = 0.028), whereas O-desmethylangolensin was positively associated with plasma estradiol level (_p² = 0.3%; P = 0.010). There were significant phytoestrogen interactions with polymorphisms in ESR1 and NR1I2 genes in affecting estrone levels. We conclude that phytoestrogens modulate sex hormone and SHBG levels in postmenopausal women and interact with gene variants involved in estrogen signaling. Such phytoestrogen-gene interactions may explain the conflicting literature on the hormonal effects of phytoestrogens. (Cancer Epidemiol Biomarkers Prev 2007;16(5):1009–16)

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