外周血中芳香烃受体及芳香烃代谢酶活性与乳腺癌关系的研究

A study on the relationship of the activity of aryl hydrocarbon receptor and aryl hydrocarbon metabolic enzymes in peripheral blood and breast cancer

背景与目的:大量研究表明,活化的芳香烃受体(aryl hydrocarbon receptor,AhR)可能参与了由多环芳烃诱导的乳腺癌的发生,AhR作为公认的配体激活的转录因子,可诱导多种酶表达。本研究旨在探讨芳香烃受体和芳香烃代谢酶在人体内蛋白水平与乳腺癌及其病理指标间的关系。方法:以1∶1配对进行病例对照研究,共收集65对血样,采用酶联免疫吸附法检测血液中芳香烃受体及芳香烃代谢酶蛋白水平,同时收集病理资料。计量资料使用秩和检验进行统计分析,相关性分析使用Spearman检验。结果:秩和检验发现对照组与病例组间醛脱氢酶(aldehyde dehydrogenase,ALDH)、细胞色素(cytochrome P450,CYP450)差异无统计学意义(Z=0.196,P=0.845;Z=0.269,P=0.788);AhR、醌氧化还原酶(quinone oxido-ereductase 1,NQO1)、谷胱甘肽-S-转移酶(glutatnione-S-transferases,GST)对照组平均浓度低于病例组,差异有统计学意义(Z=1.956,P=0.041;Z=2.627,P=0.009;Z=3.272,P=0.001)。相关性分析结果显示,病例组中AhR与GST和NQO1相关性较高(r=0.665,P<0.01;r=0.704,P<0.01)。以病理指标(ER、PR、HER-2)-、+、++、+++分组,发现以雌激素受体ER分组的AhR、GST蛋白表达水平差异有统计学意义(P<0.05)。结论:实验结果显示芳香烃受体及芳香烃代谢酶蛋白水平对乳腺癌发生可能有重要影响,检测酶蛋白水平可能对乳腺癌的早期发现有帮助,对治疗方案的选择及预后有一定意义。

Background and purpose：Previous studies showed activated aryl hydrocarbon receptor （AhR） might be involved in the development of breast cancer induced by polycyclic aromatic hydrocarbons （PHAs） and AhR which was regarded as transcription factors activated by ligand could induced many enzymes expression. Therefore, this study aimed to explore the protein level of AhR and aryl hydrocarbon metabolic enzymes in vivo with a relationship of the breast cancer and pathology indicators. Methods：A case-control study was 1∶1 matched and 65 pairs blood samples were collected, the ELISA was used in testing blood protein levels of the aromatic hydrocarbon receptor and aryl hydrocarbon metabolic enzymes. Meanwhile pathological data was collected. The Rank sum test statistical analysis was used in analyzing measurement data, Spearman test was used in correlation analysis. Results：Statistical analysis revealed that there was no statistical difference in aldehyde dehydrogenase（ALDH）, cytochrome P450（CYP450） between the case group and the control group （Z=0.196,P=0.845;Z=0.269,P=0.788）;and the AhR, NQO1, GST control group concentrations were lower than that in the case group. There were statistical differences of AhR, quinone oxido-ereductase 1（NQO1）, glutatnione-S-transferases（GST） between the control group and the case group（Z=1.956, P=0.041;Z=2.627, P=0.009;Z=3.272, P=0.001）. Correlation analysis showed that AhR has a higher correlation in case group with GST, NQO1 （r=0.665, P〈0.01;r=0.704, P〈0.01）. Grouping with the pathology indicators （ER, PR, HER-2）-,＋,＋＋,＋＋＋, found that the level of grouping by ER, AhR protein levels and GST protein levels have a discrepancies（P〈0.05）. Conclusion：These results might suggest that the protein levels of AhR and aryl hydrocarbon metabolic enzymes have a signiifcant impact on breast cancer. Detection of enzyme protein levels may be helpful for early detection of breast cancer, prompt treatment options and prognosis are meaningful.