title: Changes in 2-hydroxyestrone and 16alpha-hydroxyestrone metabolism with flaxseed consumption: modification by COMT and CYP1B1 genotype.
abstract: Consumption of the phytoestrogen lignans, structurally similar to estrogen, has been associated with alterations in gene expression and estrogen metabolism. Furthermore, lignan consumption, subsequent changes in metabolizing enzyme expression, and genetic variability in these enzymes may alter estrogen metabolism and modify disease risk. Therefore, we investigated the effect of flaxseed on hydroxyestrone metabolite excretion by catechol-O-methyltransferase (COMT) and cytochrome P450 1B1 (CYP1B1) genotype. We conducted an intervention among 132 healthy, postmenopausal women, ages 46 to 75 years. Participants consumed 10 g ground flaxseed daily for 7 consecutive days. Blood and urine samples were collected at baseline and after the 7-day intervention. COMT Val(158)Met and CYP1B1 Leu(432)Val genotypes were determined using PCR-RFLP methods. Urinary 2-hydroxyestrone (2OHE1) and 16alpha-hydroxyestrone (16OHE1) were quantified by ELISA assay. The effect of genotype on intervention-related changes in estrogen metabolites was assessed with the Kruskal-Wallis test. Compared with baseline levels, postintervention levels of urinary 2OHE1 (ng/mg creatinine; mean +/- SD, 16.1 +/- 10.6 versus 9.3 +/- 6.9, postintervention and baseline, respectively; P < 0.01) and 2OHE1/16OHE1 ratios (mean +/- SD, 2.73 +/- 1.47 versus 1.54 +/- 0.75, postintervention and baseline, respectively; P < 0.01) were significantly higher. The change in 2OHE1/16OHE1 increased with increasing numbers of variant alleles for COMT (mean change: Val/Val, 0.90; Val/Met, 1.15; and Met/Met, 1.50; P = 0.17, Kruskal-Wallis) and especially CYP1B1 (mean change: Leu/Leu, 0.89; Leu/Val, 1.32; and Val/Val, 1.51; P = 0.04, Kruskal-Wallis). Our findings suggest that variation in hormone-related genes may modify the effect of dietary lignan exposures on estrogen metabolism.
authors.affiliation: Department of Epidemiology, Roswell Park Cancer Institute, Elm and Carlton Streets, Buffalo, NY 14263, USA. susan.mccann@roswellpark.org
authors.forename: Susan E
authors.initials: SE
authors.lastname: McCann
authors.forename: Jean
authors.initials: J
authors.lastname: Wactawski-Wende
authors.forename: Kari
authors.initials: K
authors.lastname: Kufel
authors.forename: James
authors.initials: J
authors.lastname: Olson
authors.forename: Bladimir
authors.initials: B
authors.lastname: Ovando
authors.forename: Susan Nowell
authors.initials: SN
authors.lastname: Kadlubar
authors.forename: Warren
authors.initials: W
authors.lastname: Davis
authors.forename: Lisa
authors.initials: L
authors.lastname: Carter
authors.forename: Paola
authors.initials: P
authors.lastname: Muti
authors.forename: Peter G
authors.initials: PG
authors.lastname: Shields
authors.forename: Jo L
authors.initials: JL
authors.lastname: Freudenheim
mesh_terms: D000368:Aged; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics*; D002394:Catechol O-Methyltransferase / Q000235:genetics*; D065633:Cytochrome P-450 CYP1B1; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D019597:Flax; D005838:Genotype; D006801:Humans; D006894:Hydroxyestrones / Q000378:metabolism*; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D012150:Polymorphism, Restriction Fragment Length; D017698:Postmenopause; D018709:Statistics, Nonparametric
chemical_list: D006894:Hydroxyestrones; D001189:Aryl Hydrocarbon Hydroxylases; C585496:CYP1B1 protein, human; D065633:Cytochrome P-450 CYP1B1; D002394:Catechol O-Methyltransferase