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

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. Pla...

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Published in:Cancer epidemiology, biomarkers & prevention biomarkers & prevention, 2007-05, Vol.16 (5), p.1009-1016
Main Authors: LOW, Yen-Ling, DUNNING, Alison M, BINGHAML, Sheila A, DOWSETT, Mitch, FOLKERD, Elizabeth, DOODY, Deborah, TAYLOR, James, BHANIANI, Amit, LUBEN, Robert, KHAW, Kay-Tee, WAREHAM, Nick J
Format: Article
Language:English
Subjects:
Aged
Aminoacids, peptides. Hormones. Neuropeptides
Analytical, structural and metabolic biochemistry
Biological and medical sciences
Biomarkers, Tumor - blood
cross-sectional
Cross-Sectional Studies
Diet
EPIC-Norfolk
ESR1
ESR2
Female
Fundamental and applied biological sciences. Psychology
Genotype
Glycine max
Gonadal Steroid Hormones - blood
Humans
Medical sciences
Middle Aged
NR1I2
phytoestrogens
Phytoestrogens - administration & dosage
Phytoestrogens - metabolism
Phytoestrogens - urine
polymorphism
Polymorphism, Genetic
Polymorphism, Single Nucleotide
Postmenopause - blood
Postmenopause - metabolism
Pregnane X Receptor
Prospective Studies
Proteins
Receptors, Estrogen - genetics
Receptors, Steroid - genetics
Sex Hormone-Binding Globulin - analysis
Sex Hormone-Binding Globulin - metabolism
sex hormones
SHBG
Tumors
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Summary: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 ( η p 2 = 1.2%; P < 0.001) and negatively associated with plasma testosterone ( η p 2 = 0.2%; P = 0.042). Equol was negatively associated with plasma estradiol levels ( η p 2 = 0.3%; P = 0.028), whereas O -desmethylangolensin was positively associated with plasma estradiol level ( η 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. (Cancer Epidemiol Biomarkers Prev 2007;16(5):1009–16)
ISSN:1055-9965
1538-7755
DOI:10.1158/1055-9965.EPI-06-0899