Phytoestrogen exposure is associated with circulating sex hormone levels in postmenopausal women and interact with ESR1 and NR1I2 gene variants.

TitlePhytoestrogen exposure is associated with circulating sex hormone levels in postmenopausal women and interact with ESR1 and NR1I2 gene variants.
Publication TypeJournal Article
Year of Publication2007
AuthorsLow, Y-L, Dunning, AM, Dowsett, M, Folkerd, E, Doody, D, Taylor, J, Bhaniani, A, Luben, R, Khaw, K-T, Wareham, NJ, Bingham, SA
JournalCancer Epidemiol Biomarkers Prev
Volume16
Issue5
Pagination1009-16
Date Published2007 May
ISSN1055-9965
KeywordsAged, Biomarkers, Tumor, Cross-Sectional Studies, Diet, Female, Genotype, Gonadal Steroid Hormones, Humans, Middle Aged, Phytoestrogens, Polymorphism, Genetic, Polymorphism, Single Nucleotide, Postmenopause, Pregnane X Receptor, Prospective Studies, Receptors, Estrogen, Receptors, Steroid, Sex Hormone-Binding Globulin, Soybeans
Abstract

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 (eta(p)(2) = 1.2%; P < 0.001) and negatively associated with plasma testosterone (eta(p)(2) = 0.2%; P = 0.042). Equol was negatively associated with plasma estradiol levels (eta(p)(2) = 0.3%; P = 0.028), whereas O-desmethylangolensin was positively associated with plasma estradiol level (eta(p)(2) = 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.

DOI10.1158/1055-9965.EPI-06-0899
Alternate JournalCancer Epidemiol. Biomarkers Prev.
Citation Key10.1158/1055-9965.EPI-06-0899
PubMed ID17507630
Grant ListG0401527 / / Medical Research Council / United Kingdom