title: Soy isoflavones have an antiestrogenic effect and alter mammary promoter hypermethylation in healthy premenopausal women.
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.
authors.affiliation: Department of Surgery, University of Missouri School of Medicine-Columbia, One Hospital Drive, Columbia, MO 65212, USA.
authors.forename: Wenyi
authors.initials: W
authors.lastname: Qin
authors.forename: Weizhu
authors.initials: W
authors.lastname: Zhu
authors.forename: Huidong
authors.initials: H
authors.lastname: Shi
authors.forename: John E
authors.initials: JE
authors.lastname: Hewett
authors.forename: Rachel L
authors.initials: RL
authors.lastname: Ruhlen
authors.forename: Ruth S
authors.initials: RS
authors.lastname: MacDonald
authors.forename: George E
authors.initials: GE
authors.lastname: Rottinghaus
authors.forename: Yin-Chieh
authors.initials: YC
authors.lastname: Chen
authors.forename: Edward R
authors.initials: ER
authors.lastname: Sauter
mesh_terms: D000328:Adult; D001826:Body Fluids / Q000737:chemistry; D001940:Breast / Q000737:chemistry* / Q000187:drug effects; D001943:Breast Neoplasms / Q000235:genetics; D003176:Complement C3 / Q000032:analysis; D056742:Cyclin D2; D016213:Cyclins / Q000235:genetics; D019175:DNA Methylation / Q000187:drug effects / Q000235:genetics*; D004311:Double-Blind Method; D004965:Estrogen Antagonists / Q000008:administration & dosage*; D005260:Female; D019833:Genistein / Q000097:blood; D006801:Humans; D007529:Isoflavones / Q000008:administration & dosage* / Q000097:blood; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D017697:Premenopause; D011401:Promoter Regions, Genetic / Q000187:drug effects; D011446:Prospective Studies; D018168:Receptors, Retinoic Acid / Q000235:genetics; D013025:Glycine max / Q000737:chemistry*
chemical_list: C080336:CCND2 protein, human; D003176:Complement C3; D056742:Cyclin D2; D016213:Cyclins; D004965:Estrogen Antagonists; D007529:Isoflavones; D018168:Receptors, Retinoic Acid; C540966:retinoic acid receptor, beta2, human; D019833:Genistein