Changes in 2-hydroxyestrone and 16α-hydroxyestrone metabolism with flaxseed consumption:: Modification by COMT and CYP1B1 genotype

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 (CYP1131) genotype. We conducted an intervention among 132 healthy, postmenopausal women, ages 46 to 75 years. Participants consumed 10 9 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 (20HE1) and 16 alpha-hydroxyestrone (160HE1) were quantified by ELISA assay. The effect ofgenotype on intervention-related changes in estrogen metabolites was assessed with the Kruskal-Wallis test. Compared with baseline levels, postintervention levels of urinary 20HE1 (ng/mg creatinine; mean +/- SD, 16.1 +/- 10.6 versus 9.3 +/- 6.9, postintervention and baseline, respectively; P < 0.01) and 20HE1/16OHE1 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 20HE1/16OHE1 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.