Lipid peroxidation and glutathione peroxidase activity relationship in breast cancer depends on functional polymorphism of GPX1.
Lipid peroxidation and glutathione peroxidase activity relationship in breast cancer depends on functional polymorphism of GPX1.
复制标题
DOI：
10.1186/s12885-015-1680-4
复制
发表时间：
2015-10-07
期刊：
影响因子：
3.8
通讯作者：
Wasowicz W
中科院分区：
文献类型：
--
作者：
Jablonska E;Gromadzinska J;Peplonska B;Fendler W;Reszka E;Krol MB;Wieczorek E;Bukowska A;Gresner P;Galicki M;Zambrano Quispe O;Morawiec Z;Wasowicz W
由于靶向氧化应激标记物最近被认为是癌症的新治疗靶点，因此研究遗传易感性是否可以改变癌症中的氧化应激反应是有趣的。本研究的目的是阐明抗氧化酶的遗传多态性是否与乳腺癌的脂质过氧化反应有关。我们在波兰妇女中进行了一项研究，包括136例乳腺癌病例和183例健康对照。分析包括五个氧化还原相关基因的遗传多态性：GPX 1（rs 1050450），GPX 4（rs713041），SOD 2（rs 4880），SEP 1（rs3877899）和SEP 15（rs 5859），脂质过氧化，血液室中测定的抗氧化酶活性以及血浆硒浓度-一种与癌症有关的抗氧化微量元素。使用真实的时间PCR进行基因分型。脂质过氧化反应表示为血浆浓度的硫代巴比妥酸反应物质（TBARS），并与荧光分光光度法测量。采用Paglia和Valentine方法，通过比色法测定红细胞（GPx 1）和血浆（GPx 3）中的谷胱甘肽过氧化物酶活性。采用分光光度法测定红细胞胞浆超氧化物歧化酶（SOD 1）活性（Beauchamp和Fridovich法）和血浆铜蓝蛋白（Cp）活性（Sunderman和Nomoto法）。采用石墨炉原子吸收分光光度法测定血浆硒浓度。GPX 1 rs 1050450（Pro 198 Leu）多态性与乳腺癌风险显著相关，显示变异（Leu）等位基因的保护作用。与对照组相比，乳腺癌患者的脂质过氧化和GPx 1活性显著升高，而铜蓝蛋白活性降低。基因型分层后，GPX 1 Pro/Pro纯合子乳腺癌患者的GPx 1活性和TBARS浓度均最高。同时，在具有GPX 1 Pro/Pro基因型的癌症受试者中，脂质过氧化水平与GPx 1活性之间存在显著相关性（r = 0.3043; p = 0.0089），而在携带至少一个GPX 1 Leu等位基因的病例中以及在对照组中（无论GPX 1基因型如何），这种相关性完全不存在。GPX 1基因多态性可能是乳腺癌患者氧化应激反应的重要调节因子。需要进一步的研究来阐明其潜在的临床意义。本文的在线版本（doi：10.1186/s12885-015-1680-4）包含补充材料，可供授权用户使用。
Since targeting oxidative stress markers has been recently recognized as a novel therapeutic target in cancer, it is interesting to investigate whether genetic susceptibility may modify oxidative stress response in cancer. The aim of this study was to elucidate whether genetic polymorphism in the antioxidant enzymes is associated with lipid peroxidation in breast cancer. We conducted a study among Polish women, including 136 breast cancer cases and 183 healthy controls. The analysis included genetic polymorphisms in five redox related genes: GPX1 (rs1050450), GPX4 (rs713041), SOD2 (rs4880), SEPP1 (rs3877899) and SEP15 (rs5859), lipid peroxidation, the activities of antioxidant enzymes determined in blood compartments as well as plasma concentration of selenium – an antioxidant trace element involved in cancer. Genotyping was performed using the Real Time PCR. Lipid peroxidation was expressed as plasma concentration of thiobarbituric acid reactive substances (TBARS) and measured with the spectrofluorometric method. Glutathione peroxidase activity was spectrophotometrically determined in erythrocytes (GPx1) and plasma (GPx3) by the use of Paglia and Valentine method. Spectrophotometric methods were employed to measure activity of cytosolic superoxide dismutase (SOD1) in erythrocytes (Beauchamp and Fridovich method) and ceruloplasmin (Cp) in plasma (Sunderman and Nomoto method). Plasma selenium concentration was determined using graphite furnace atomic absorption spectrophotometry. Breast cancer risk was significantly associated with GPX1 rs1050450 (Pro198Leu) polymorphism, showing a protective effect of variant (Leu) allele. As compared to the control subjects, lipid peroxidation and GPx1 activity were significantly higher in the breast cancer cases, whereas ceruloplasmin activity was decreased. After genotype stratification, both GPx1 activity and TBARS concentration were the highest in GPX1 Pro/Pro homozygotes affected by breast cancer. At the same time, there was a significant correlation between the level of lipid peroxidation and GPx1 activity among the cancer subjects possessing GPX1 Pro/Pro genotype (r = 0.3043; p = 0.0089), whereas such a correlation was completely absent in the cases carrying at least one GPX1 Leu allele as well as in the controls (regardless of GPX1 genotype). GPX1 polymorphism may be an important factor modifying oxidative stress response in breast cancer subjects. Further studies are needed to elucidate its potential clinical significance. The online version of this article (doi:10.1186/s12885-015-1680-4) contains supplementary material, which is available to authorized users.