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评估前列腺癌患者血液和组织样本中谷胱甘肽-S-转移酶基因的多态性状态。

Evaluating polymorphic status of glutathione-S-transferase genes in blood and tissue samples of prostate cancer patients.

作者信息

Mittal Rama Devi, Mishra Dhruva K, Mandhani Anil

机构信息

Department of Urology, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow-226014, India.

出版信息

Asian Pac J Cancer Prev. 2006 Jul-Sep;7(3):444-6.

PMID:17059341
Abstract

Prostate cancer is the most common urologic malignancy, involving multiple factors. There is evidence that suggests that detoxification enzymes and growth factors may play a role in its development . The glutathione S-transferase (GST) enzymes detoxify several carcinogens and genetic polymorphisms in GSTM1, T1, and P1 (Ile105Val) have been reported to be associated with prostate cancer, mainly from blood samples. As expression studies suggest differential expression of different genes in tissues, we hypothesize that polymorphic status may be differently expressed for GSTM1, GSTT1 and GSTP1 gene in blood and tissues of prostate cancer patients and BPH controls, impacting on the development of prostate cancer. To study this, we extracted DNA from blood and tissue samples of patients undergoing biopsy procedures or transurethral resection of prostate tissue. Genotyping for GSTM1 and T1 was conducted by multiplex PCR and for GSTP1 by the PCR-RFLP method. Our results suggested no significant differences in frequency distribution of M1, T1 and P1 between blood and tissue samples of patients and controls, but in a few patients differences in polymorphic status were observed. However, they were not significant. Furthermore, we observed a significant risk of prostate cancer with null allele of GSTT1 and GSTM1 and Val allele of GSTP1, supporting our previous findings. A study with large sample size using radical prostectomy tissue now needs to be performed to attain a specific conclusion.

摘要

前列腺癌是最常见的泌尿系统恶性肿瘤,涉及多种因素。有证据表明解毒酶和生长因子可能在其发展过程中发挥作用。谷胱甘肽S-转移酶(GST)可使多种致癌物解毒,并且据报道GSTM1、T1和P1(Ile105Val)中的基因多态性与前列腺癌相关,主要来自血液样本。由于表达研究表明不同基因在组织中存在差异表达,我们推测前列腺癌患者和良性前列腺增生(BPH)对照者的血液和组织中GSTM1、GSTT1和GSTP1基因的多态性状态可能存在差异表达,从而影响前列腺癌的发展。为了研究这一点,我们从接受活检程序或经尿道前列腺组织切除术的患者的血液和组织样本中提取了DNA。通过多重PCR对GSTM1和T1进行基因分型,通过PCR-RFLP方法对GSTP1进行基因分型。我们的结果表明,患者和对照者的血液和组织样本中M1、T1和P1的频率分布没有显著差异,但在少数患者中观察到了多态性状态的差异。然而,这些差异并不显著。此外,我们观察到携带GSTT1和GSTM1无效等位基因以及GSTP1 Val等位基因的患者患前列腺癌的风险显著增加,这支持了我们之前的发现。现在需要进行一项使用根治性前列腺切除术组织的大样本研究以得出具体结论。

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