National Environmental Health Research Center (NEHRC), National Health Research Institutes (NHRI), Miaoli, Taiwan.
Environ Sci Pollut Res Int. 2014 Dec;21(24):13964-73. doi: 10.1007/s11356-014-3260-6. Epub 2014 Jul 18.
Evidence has shown that polymorphisms of various genes known to be involved in estrogen biosynthesis and function are associated with estrogen-dependent diseases (EDDs). These genes include CYP17A1, estrogen receptor 1 (ESR1), and 2 (ESR2). Phthalates are considered estrogenic endocrine disruptors, and recent research has suggested that they may act as a risk factor for EDDs. However, extremely few studies have assessed the effects of gene-environment interaction on these diseases. We recruited 44 patients with endometriosis or adenomyosis, 36 patients with leiomyoma, and 69 healthy controls from a medical center in Taiwan between 2005 and 2007. Urine samples were collected and analyzed for seven phthalate metabolites using liquid chromatography tandem mass spectrometry. Peripheral lymphocytes were used for DNA extraction to determine the genotype of CYP17A1, ESR1, and ESR2. Compared to controls, patients with leiomyoma had significantly higher levels of total urinary mono-ethylhexyl phthalate (ΣMEHP) (52.1 vs. 29.6 μg/g creatinine, p = 0.040), mono-n-butyl phthalate (MnBP) (75.4 vs. 51.3 μg/g creatinine, p = 0.019), and monoethyl phthalate (MEP) (103.7 vs. 59.3 μg/g creatinine, p = 0.031). In contrast, patients with endometriosis or adenomyosis showed a marginally increased level of urinary MEHP only. Subjects who were homozygous for both the ESR1 C allele (rs2234693) and CYP17A1 C allele (rs743572) showed a significantly increased risk for leiomyoma (OR = 19.8; 95 % CI, 1.70; 231.5; p = 0.017) relative to subjects with other genotypes of ESR1 and CYP17A1. These results were obtained after adjusting for age, cigarette smoking, MEHP level, GSTM1 genotype and other covariates. Our results suggested that both CYP17A1 and ESR1 polymorphisms may modulate the effects of phthalate exposure on the development of leiomyoma.
证据表明，已知参与雌激素生物合成和功能的各种基因的多态性与雌激素依赖性疾病（EDD）有关。这些基因包括 CYP17A1、雌激素受体 1（ESR1）和 2（ESR2）。邻苯二甲酸酯被认为是具有雌激素活性的内分泌干扰物，最近的研究表明它们可能是 EDD 的危险因素。然而，极少数研究评估了基因-环境相互作用对这些疾病的影响。我们于 2005 年至 2007 年期间在台湾的一家医疗中心招募了 44 名子宫内膜异位症或子宫腺肌病患者、36 名子宫肌瘤患者和 69 名健康对照者。收集尿液样本，并用液相色谱-串联质谱法分析七种邻苯二甲酸代谢物。使用外周淋巴细胞提取 DNA，以确定 CYP17A1、ESR1 和 ESR2 的基因型。与对照组相比，子宫肌瘤患者的总尿单乙基己基邻苯二甲酸酯（ΣMEHP）水平明显升高（52.1 与 29.6 μg/g 肌酐，p = 0.040），单正丁基邻苯二甲酸酯（MnBP）（75.4 与 51.3 μg/g 肌酐，p = 0.019）和单乙基邻苯二甲酸酯（MEP）（103.7 与 59.3 μg/g 肌酐，p = 0.031）。相比之下，子宫内膜异位症或子宫腺肌病患者仅显示出尿液中 MEHP 水平略有升高。同时携带 ESR1 C 等位基因（rs2234693）和 CYP17A1 C 等位基因（rs743572）的受试者发生子宫肌瘤的风险显著增加（OR = 19.8；95%CI，1.70；231.5；p = 0.017）与具有其他 ESR1 和 CYP17A1 基因型的受试者相比。这些结果是在调整年龄、吸烟、MEHP 水平、GSTM1 基因型和其他协变量后得出的。我们的结果表明，CYP17A1 和 ESR1 多态性可能调节邻苯二甲酸酯暴露对子宫肌瘤发生的影响。
