title: Polymorphisms in the CYP19 gene may affect the positive correlations between serum and urine phytoestrogen metabolites and plasma androgen concentrations in men.
abstract: Phytoestrogens have been hypothesized to protect against prostate cancer via modulation of circulating androgen concentrations. We conducted a cross-sectional study of 267 men in the Norfolk arm of the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort with 2 aims: first, to investigate the association between phytoestrogen exposure (measured from diet, urine, and serum) and plasma concentrations of sex hormone-binding globulin (SHBG), androstanediol glucuronide, testosterone and Free Androgen Index (FAI); and second, whether the association may be modified by polymorphisms in CYP19 and SHBG genes. Dietary daidzein and genistein intakes were obtained from food diaries and computed using an in-house food composition database. Urinary and serum concentrations of 3 isoflavones (daidzein, genistein, glycitein), 2 daidzein metabolites O-desmethylangolensin (O-DMA) and 2 lignan metabolites (enterodiol and enterolactone) were measured using mass spectrometry. There was no association between dietary, urinary, and serum phytoestrogens and plasma SHBG concentrations. Enterolactone was positively associated with plasma androstanediol glucuronide concentrations (urinary enterolactone: r = 0.127, P = 0.043; serum enterolactone: r = 0.172, P = 0.006) and FAI (urinary enterolactone: r = 0.115, P = 0.067; serum enterolactone: r = 0.158, P = 0.011). Both urinary and serum equol were associated with plasma testosterone (urinary equol: r = 0.332, P = 0.013; serum equol: r = 0.318, P = 0.018) and FAI (urinary equol: r = 0.297, P = 0.027; serum equol: r = 0.380, P = 0.004) among men with the TT genotype but not the CC or CT genotypes (r = -0.029 to -0.134, P = 0.091-0.717) for the CYP19 3'untranslated region (UTR) T-C polymorphism. Urinary and serum enterolactone showed similar genotype-dependent associations with testosterone but not with FAI. In this first study on phytoestrogen-gene associations in men, we conclude that enterolactone and equol are positively associated with plasma androgen concentrations, and interactions with CYP19 gene may be involved.
authors.affiliation: MRC Dunn Human Nutrition Unit, Cambridge, 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: Elizabeth
authors.initials: E
authors.lastname: Folkerd
authors.forename: Deborah
authors.initials: D
authors.lastname: Doody
authors.forename: Alison M
authors.initials: AM
authors.lastname: Dunning
authors.forename: Serena
authors.initials: S
authors.lastname: Scollen
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: D015107:4-Butyrolactone / Q000031:analogs & derivatives / Q000097:blood / Q000652:urine; D000368:Aged; D000728:Androgens / Q000097:blood*; D015113:Androstane-3,17-diol / Q000031:analogs & derivatives / Q000097:blood; D001141:Aromatase / Q000235:genetics*; D004032:Diet; D060754:Equol; D019833:Genistein / Q000008:administration & dosage; D005838:Genotype; D006801:Humans; D007529:Isoflavones / Q000008:administration & dosage / Q000097:blood / Q000652:urine; D017705:Lignans / Q000097:blood / Q000652:urine; D008297:Male; D008875:Middle Aged; D048789:Phytoestrogens / Q000008:administration & dosage / Q000097:blood* / Q000652:urine*; D011110:Polymorphism, Genetic / Q000235:genetics*; D012738:Sex Hormone-Binding Globulin / Q000032:analysis; D013739:Testosterone / Q000097:blood
chemical_list: C007610:4',7-dihydroxy-3,4-dihydroisoflavone; D000728:Androgens; D007529:Isoflavones; D017705:Lignans; D048789:Phytoestrogens; D012738:Sex Hormone-Binding Globulin; D015113:Androstane-3,17-diol; C028895:androstane-3,17-diol glucuronide; D013739:Testosterone; D060754:Equol; C004742:daidzein; D019833:Genistein; D001141:Aromatase; D015107:4-Butyrolactone; C029497:2,3-bis(3'-hydroxybenzyl)butyrolactone