title: Phytoestrogen exposure correlation with plasma estradiol in postmenopausal women in European Prospective Investigation of Cancer and Nutrition-Norfolk may involve diet-gene interactions.
abstract: Cross-sectional studies investigating the relationship between phytoestrogens in diet, urine, or blood with plasma estradiol and sex hormone binding globulin (SHBG) have been inconclusive. We investigated the relationship among phytoestrogen exposure, polymorphisms in the ESR1, COMT, CYP19, and SHBG genes, and plasma estradiol and SHBG levels in 125 free-living postmenopausal women taking part in a cohort study (European Prospective Investigation of Cancer and Nutrition-Norfolk) using three different markers: dietary, urinary, and serum phytoestrogens. Phytoestrogen levels (daidzein, genistein, glycitein, O-desmethylangolensin, equol, enterodiol, and enterolactone) in spot urine and serum were analyzed by gas chromatography/mass spectrometry and liquid chromatography/tandem mass spectrometry, respectively. Plasma estradiol and SHBG were measured by immunoassays. Adjusting for age and body mass index, urinary daidzein, genistein, glycitein, and serum daidzein and glycitein were negatively correlated with plasma estradiol (R = -0.199 to -0.277, P <0.03), with particularly strong associations found in the 18 women with CC genotype for ESR1 PvuII polymorphism (R = -0.597 to -0.834, P < 0.03). The negative correlations observed between isoflavones and estradiol in women as a whole became no longer significant when we excluded women with ESR1 PvuII CC genotype, indicating that the correlations observed were due mainly to this group of women. There was no relationship between dietary isoflavones and plasma estradiol and no association was found between any of the dietary, urinary, and serum phytoestrogen and plasma SHBG or between these factors and polymorphisms in CYP19, SHBG, and COMT. We conclude that higher isoflavone exposure is associated with lower plasma estradiol in postmenopausal women and that this preliminary study is suggestive of the involvement of diet-gene interactions.
authors.affiliation: Medical Research Council Dunn Human Nutrition Unit, Wellcome Trust/Medical Research Council Building, Hills Road, Cambridge CB2 2XY, United Kingdom. sab@mrc-dunn.cam.ac.uk
authors.forename: Yen-Ling
authors.initials: YL
authors.lastname: Low
authors.forename: James I
authors.initials: JI
authors.lastname: Taylor
authors.forename: Philip B
authors.initials: PB
authors.lastname: Grace
authors.forename: Mitch
authors.initials: M
authors.lastname: Dowsett
authors.forename: Serena
authors.initials: S
authors.lastname: Scollen
authors.forename: Alison M
authors.initials: AM
authors.lastname: Dunning
authors.forename: Angela A
authors.initials: AA
authors.lastname: Mulligan
authors.forename: Ailsa A
authors.initials: AA
authors.lastname: Welch
authors.forename: Robert N
authors.initials: RN
authors.lastname: Luben
authors.forename: Kay-Tee
authors.initials: KT
authors.lastname: Khaw
authors.forename: Nick E
authors.initials: NE
authors.lastname: Day
authors.forename: Nick J
authors.initials: NJ
authors.lastname: Wareham
authors.forename: Sheila A
authors.initials: SA
authors.lastname: Bingham
mesh_terms: D000368:Aged; D000704:Analysis of Variance; D014408:Biomarkers, Tumor / Q000097:blood; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism*; D002849:Chromatography, Gas; D003430:Cross-Sectional Studies; D004032:Diet; D004958:Estradiol / Q000097:blood*; D005060:Europe; D005260:Female; D005838:Genotype; D006801:Humans; D013058:Mass Spectrometry; D008875:Middle Aged; D048789:Phytoestrogens / Q000008:administration & dosage / Q000378:metabolism*; D011110:Polymorphism, Genetic; D017698:Postmenopause; D011446:Prospective Studies; D012738:Sex Hormone-Binding Globulin / Q000378:metabolism; D018709:Statistics, Nonparametric
chemical_list: D014408:Biomarkers, Tumor; D048789:Phytoestrogens; D012738:Sex Hormone-Binding Globulin; D004958:Estradiol