金属雌激素、GSTP1 和 SLC11A2 多态性与子宫内膜癌风险的关联。
The Associations between Metalloestrogens, GSTP1, and SLC11A2 Polymorphism and the Risk of Endometrial Cancer.
机构信息
Department of Gynecological Surgery and Gynecological Oncology of Adults and Adolescents, Pomeranian Medical University, 70-111 Szczecin, Poland.
Department of Biochemistry and Medical Chemistry, Pomeranian Medical University, Powstańców Wielkopolskich. 72, 70-111 Szczecin, Poland.
出版信息
Nutrients. 2022 Jul 27;14(15):3079. doi: 10.3390/nu14153079.
BACKGROUND
The incidence of endometrial cancer (EC) is still rising. Numerous risk factors including patient characteristics and molecular instability have been identified for EC. The presence of specific molecular markers allows specific diagnostic and prognostic approaches. Several single nucleotide polymorphisms (SNPs) have been identified to influence endometrial cancer risk. Metalloestrogens are metal ions which can mimic estrogen activity; however, their role in uterine pathologies remains unknown. This study aimed to investigate total blood trace elements levels and evaluate the distribution of selected genotypes in GSTP1 and SLC11A2 genes.
METHODS
This retrospective case-control analysis was carried out in peripheral blood samples of 110 women with endometrial cancer (EC; = 21), uterine fibroma ( = 25), endometrial polyp ( = 48), and normal endometrium ( = 16). Analysis included measurement of metals and phosphor in serum, and of genetic polymorphisms in GST (rs1695) and SLC11A2 (rs224589) in DNA from white blood cells. Serum trace elements were measured using ICP-OES spectrometry. SNPs were identified using Taq Man real-time PCR genotyping assays.
RESULTS
The study confirmed higher age (OR 2.19, 95% CI 1.69-2.24), post-menopausal status (OR 1.89, 95% CI 1.36-1.94), and diabetes type 2 (OR 1.54; 95% CI 0.97-1.72) as independent risk factors for EC. We also found a high level of Cd (OR 1.49; 95% CI 1.31-1.63) and a low level of Co (OR 0.76; 95% CI 0.53-0.59) to be independent risk factors of EC. None of the tested polymorphisms of GSTP1 and SLC11A2 were associated with EC risk. However, high Cd (OR 1.21, 95% CI 1.15-1.29) and Ni (OR 1.07, 95% CI 1.05-1.18) serum levels were significantly associated with a SLC1A2 TG genotype, and high Cd levels with GSTP1 (OR 1.05, 95% CI 1.01-1.13).
背景
子宫内膜癌（EC）的发病率仍在上升。已经确定了许多与 EC 相关的风险因素，包括患者特征和分子不稳定性。特定的分子标志物的存在允许特定的诊断和预后方法。已经发现了几种单核苷酸多态性（SNP）来影响子宫内膜癌的风险。金属雌激素是可以模拟雌激素活性的金属离子;然而，它们在子宫病理学中的作用仍然未知。本研究旨在调查全血微量元素水平，并评估 GSTP1 和 SLC11A2 基因中选定基因型的分布。
方法
这是一项回顾性病例对照分析，在 110 名患有子宫内膜癌（EC； = 21）、子宫肌瘤（ = 25）、子宫内膜息肉（ = 48）和正常子宫内膜（ = 16）的女性的外周血样本中进行。分析包括测量血清中的金属和磷，以及白细胞 DNA 中的 GST（rs1695）和 SLC11A2（rs224589）的遗传多态性。使用 ICP-OES 光谱法测量血清微量元素。使用 Taq Man 实时 PCR 基因分型检测 SNP。
结果
该研究证实年龄较大（OR 2.19，95%CI 1.69-2.24）、绝经后状态（OR 1.89，95%CI 1.36-1.94）和 2 型糖尿病（OR 1.54; 95%CI 0.97-1.72）是 EC 的独立危险因素。我们还发现 Cd 水平较高（OR 1.49; 95%CI 1.31-1.63）和 Co 水平较低（OR 0.76; 95%CI 0.53-0.59）是 EC 的独立危险因素。GSTP1 和 SLC11A2 测试的多态性均与 EC 风险无关。然而，高 Cd（OR 1.21，95%CI 1.15-1.29）和 Ni（OR 1.07，95%CI 1.05-1.18）血清水平与 SLC1A2 TG 基因型显著相关，高 Cd 水平与 GSTP1 相关（OR 1.05，95%CI 1.01-1.13）。
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