Changes in 2-hydroxyestrone and 16alpha-hydroxyestrone metabolism with flaxseed consumption: modification by COMT and CYP1B1 genotype.
Changes in 2-hydroxyestrone and 16alpha-hydroxyestrone metabolism with flaxseed consumption: modification by COMT and CYP1B1 genotype.
复制标题
2-羟基雌酮和 16α-羟基雌酮代谢随亚麻籽消耗的变化：COMT 和 CYP1B1 基因型的修饰。
DOI：
10.1158/1055-9965.epi-06-0633
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发表时间：
2007
期刊：
影响因子：
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通讯作者：
Freudenheim,JoL
中科院分区：
文献类型：
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作者：
McCann,SusanE;Wactawski-Wende,Jean;Kufel,Kari;Olson,James;Ovando,Bladimir;Kadlubar,SusanNowell;Davis,Warren;Carter,Lisa;Muti,Paola;Shields,PeterG;Freudenheim,JoL
与雌激素结构相似的植物雌激素木脂素的摄入与基因表达和雌激素代谢的改变有关。此外，木脂素的消耗、随后代谢酶表达的变化以及这些酶的遗传变异可能改变雌激素代谢并改变疾病风险。因此，我们通过儿茶酚- o -甲基转移酶（COMT）和细胞色素p450 1B1 （CYP1B1）基因型研究了亚麻籽对羟孕酮代谢物排泄的影响。我们对132名46至75岁的健康绝经后妇女进行了干预。参与者连续7天每天食用10克亚麻籽。在基线和干预7天后采集血样和尿样。COMT Val158MetandCYP1B1 leu432valgentypes采用PCR-RFLP方法测定。采用ELISA法测定尿2-羟孕酮（2OHE1）和16α-羟孕酮（16OHE1）含量。通过Kruskal-Wallis试验评估基因型对干预相关雌激素代谢物变化的影响。与基线水平相比，干预后尿2OHE1水平（ng/mg肌酐，平均±SD， 16.1±10.6 vs 9.3±6.9，干预后和基线，P< 0.01）和2OHE1/ 16ohe1比值（平均±SD， 2.73±1.47 vs 1.54±0.75，干预后和基线，P< 0.01）显著升高。随着comt变异等位基因数量的增加（平均变化：Val/Val，0.90;Val/Met,1.15; Met/Met,1.50；P= 0.17, Kruskal-Wallis），特别是cyp1b1（平均变化：Leu/Leu，0.89;Leu/Val,1.32; Val/Val, 1.51；P= 0.04, Kruskal-Wallis）， 2OHE1/16OHE1的变化也随之增加。我们的研究结果表明，激素相关基因的变异可能会改变饮食中木脂素暴露对雌激素代谢的影响。（癌症流行病学杂志，2007;16(2):256-62）
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 cytochromeP450 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 Val158MetandCYP1B1 Leu432Valgenotypes were determined using PCR-RFLP methods. Urinary 2-hydroxyestrone (2OHE1) and 16α-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 forCOMT(mean change:Val/Val,0.90;Val/Met,1.15; andMet/Met,1.50;P= 0.17, Kruskal-Wallis) and especiallyCYP1B1(mean change:Leu/Leu,0.89;Leu/Val,1.32; andVal/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. (Cancer Epidemiol Biomarkers Prev 2007;16(2):256–62)