This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Low, Y.-L. Articles by Bingham, S. A. Search for Related Content PubMed PubMed Citation Articles by Low, Y.-L. Articles by Bingham, S. A.

Phytoestrogen Exposure Correlation with Plasma Estradiol in Postmenopausal Women in European Prospective Investigation of Cancer and Nutrition-Norfolk May Involve Diet-Gene Interactions

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

Requests for reprints: Sheila A. Bingham, Medical Research Council Dunn Human Nutrition Unit, Wellcome Trust/Medical Research Council 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

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.

Key Words: cross-sectional • diet • phytoestrogens • estradiol • SHBG • polymorphism • EPIC-Norfolk • CYP19 • SHBG • COMT • ESR1

This article has been cited by other articles:

				M. Hedelin, M. Lof, M. Olsson, H. Adlercreutz, S. Sandin, and E. Weiderpass Dietary Phytoestrogens Are Not Associated with Risk of Overall Breast Cancer But Diets Rich in Coumestrol Are Inversely Associated with Risk of Estrogen Receptor and Progesterone Receptor Negative Breast Tumors in Swedish Women J. Nutr., May 1, 2008; 138(5): 938 - 945. [Abstract] [Full Text] [PDF]

				C. Duffy, K. Perez, and A. Partridge Implications of Phytoestrogen Intake for Breast Cancer CA Cancer J Clin, September 1, 2007; 57(5): 260 - 277. [Abstract] [Full Text] [PDF]

				Y.-L. Low, A. M. Dunning, M. Dowsett, E. Folkerd, D. Doody, J. Taylor, A. Bhaniani, R. Luben, K.-T. Khaw, N. J. Wareham, et al. Phytoestrogen Exposure Is Associated with Circulating Sex Hormone Levels in Postmenopausal Women and Interact with ESR1 and NR1I2 Gene Variants Cancer Epidemiol. Biomarkers Prev., May 1, 2007; 16(5): 1009 - 1016. [Abstract] [Full Text] [PDF]

				P. H. M. Peeters, N. Slimani, Y. T. van der Schouw, P. B. Grace, C. Navarro, A. Tjonneland, A. Olsen, F. Clavel-Chapelon, M. Touillaud, M.-C. Boutron-Ruault, et al. Variations in Plasma Phytoestrogen Concentrations in European Adults J. Nutr., May 1, 2007; 137(5): 1294 - 1300. [Abstract] [Full Text] [PDF]

				M. S. Touillaud, A. C. M. Thiebaut, A. Fournier, M. Niravong, M.-C. Boutron-Ruault, and F. Clavel-Chapelon Dietary Lignan Intake and Postmenopausal Breast Cancer Risk by Estrogen and Progesterone Receptor Status J Natl Cancer Inst, March 21, 2007; 99(6): 475 - 486. [Abstract] [Full Text] [PDF]

				M. Verheus, C. H. van Gils, L. Keinan-Boker, P. B. Grace, S. A. Bingham, and P. H.M. Peeters Plasma Phytoestrogens and Subsequent Breast Cancer Risk J. Clin. Oncol., February 20, 2007; 25(6): 648 - 655. [Abstract] [Full Text] [PDF]

				S. E. McCann, J. Wactawski-Wende, K. Kufel, J. Olson, B. Ovando, S. N. Kadlubar, W. Davis, L. Carter, P. Muti, P. G. Shields, et al. Changes in 2-Hydroxyestrone and 16{alpha}-Hydroxyestrone Metabolism with Flaxseed Consumption: Modification by COMT and CYP1B1 Genotype Cancer Epidemiol. Biomarkers Prev., February 1, 2007; 16(2): 256 - 262. [Abstract] [Full Text] [PDF]

				Y.-L. Low, A. M. Dunning, M. Dowsett, R. N. Luben, K.-T. Khaw, N. J. Wareham, and S. A. Bingham Implications of Gene-Environment Interaction in Studies of Gene Variants in Breast Cancer: An Example of Dietary Isoflavones and the D356N Polymorphism in the Sex Hormone-Binding Globulin Gene. Cancer Res., September 15, 2006; 66(18): 8980 - 8983. [Abstract] [Full Text] [PDF]