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Cited by 138Phytoestrogen effects and researchEstrogen and related hormone effectsEpigenetics and DNA Methylation

Soy isoflavones have an antiestrogenic effect and alter mammary promoter hypermethylation in healthy premenopausal women

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Qin, Wenyi, Zhu, Weizhu, Shi, Huidong, Hewett, John E., Ruhlen, Rachel L., MacDonald, Ruth S., Rottinghaus, George E., Chen, Yin-Chieh +1 more·2009·Nutrition and Cancer
DOI 10.1080/01635580802404196PMC PMC3390914
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Abstract

We determined if soy isoflavones have dose-related estrogenic and methylation effects. Thirty-four healthy premenopausal women were randomized to 40 mg or 140 mg isoflavones daily through one menstrual cycle. Breast specific and systemic estrogenic effects were assessed measuring the estrogenic marker complement (C)3 and changes in cytology, whereas methylation assessment of 5 cancer related genes (p16, RASSF1A, RARbeta2, ER, and CCND2) was performed on intraductal specimens. Serum genistein significantly increased after consuming both isoflavone doses. Cytology did not significantly change at either isoflavone dose. Serum C3 levels posttreatment were inversely related to change in serum genistein (r =-0.76, P = 0.0045) in women consuming low but not high dose isoflavones. The RAR beta 2 hypermethylation increase posttreatment correlated with the posttreatment genistein level considering the entire group (r = 0.67, P = 0.0017) and those receiving high-dose isoflavones (r = 0.68, P = 0.021). At the low but not the high isoflavone dose, CCND2 hypermethylation increase correlated with posttreatment genistein levels (r = 0.79, P = 0.011). In summary, the inverse correlation between C3 and genistein suggests an antiestrogenic effect. Isoflavones induced dose-specific changes in RARbeta2 and CCND2 gene methylation, which correlated with genistein levels. This work provides novel insights into estrogenic and methylation effects of dietary isoflavones.

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  • Preclinical evidence shows that under high estrogen concentrations similar to premenopausal levels, soy isoflavones act as ER antagonists, while under low estrogen concentrations comparable to postmenopausal levels, they are ER agonists.

    “Secondly, preclinical evidence has shown that under conditions of high estrogen concentration similar to premenopausal levels, soy isoflavones act as ER antagonists, while under conditions of low estrogen comparable to postmenopausal levels, they are ER agonists [12,181,182].”

    From Soy, Red Clover, and Isoflavones and Breast Cancer: A Systematic Review (2013) · cites this paper as [182]

    The Discussion (page not provided) reports preliminary evidence of an antiestrogenic effect in healthy premenopausal women, supporting one part of the claim. The paper does not establish that ER activity switches with estrogen concentration or that soy isoflavones act as ER agonists under postmenopausal-level estrogen; its discussion of differing effects concerns isoflavone dose and circulating genistein levels, not estrogen levels. (LLM, conf=0.86)

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Cited by

Sorted by citations

Authors
Qin, W., Zhu, W., Shi, H., Hewett, J. E., Ruhlen, R. L., MacDonald, R. S., Rottinghaus, G. E., Chen, Y.-C., & Sauter, E. R.
Affiliations
  • University of Missouri (US)
  • Iowa State University (US)
ORCID
Venue
Nutrition and Cancer
Publisher
Informa UK Limited
Published
2009-02-21
Volume
61
Issue
2
Pages
238-244
ISSN
  • 0163-5581 (ISSN-L)
  • 1532-7914
DOI
10.1080/01635580802404196
PMC
PMC3390914
OpenAlex
W1976726102
Cited by
138
References
0
Citations by year
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FWCI
7.99
Type
journal article
Language
en
Open access
Locations
  • Nutrition and Cancer (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
  • Iowa State University Digital Repository (Iowa State University) (submittedVersion)
Funders
  • National Institutes of Health
  • National Cancer Institute (R21CA105330, CA 105330)
Topics
  • Health Sciences › Medicine › Pathology and Forensic Medicine › Phytoestrogen effects and research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Estrogen and related hormone effects
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
Keywords
soy isoflavones, genistein, antiestrogenic effects, DNA methylation, premenopausal women, estrogenic activity, complement C3, RARβ2, cyclin D2, p16, RASSF1A, breast cancer prevention
MeSH terms
Adult, Body Fluids, Breast, Breast Neoplasms, Complement C3, Double-Blind Method, Estrogen Antagonists, Female, Humans, Isoflavones, Middle Aged, Promoter Regions, Genetic, Prospective Studies, Glycine max, Polymerase Chain Reaction, Cyclins, Premenopause, Receptors, Retinoic Acid, DNA Methylation, Genistein, Cyclin D2

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