Bumbasirevic Uros, Bojanic Nebojsa, Pljesa-Ercegovac Marija, Zivkovic Marko, Djukic Tatjana, Zekovic Milica, Milojevic Bogomir, Kajmakovic Boris, Janicic Aleksandar, Simic Tatjana, Coric Vesna
Clinic of Urology, University Clinical Center of Serbia, 11000 Belgrade, Serbia.
Faculty of Medicine, University of Belgrade, 11000 Belgrade, Serbia.
Cancers (Basel). 2022 Feb 20;14(4):1068. doi: 10.3390/cancers14041068.
The simultaneous analysis of redox biomarkers and polymorphisms encoding for regulatory and catalytic antioxidant proteins was performed in order to evaluate their potential role in the development of testicular germ cell tumor (GCT), as well as the progression of the disease. (rs6721961), (rs1332018), (rs4880) and (rs8177412) polymorphisms were assessed in 88 patients with testicular GCT (52 with seminoma) and 88 age-matched controls. The plasma levels of 8-hydroxy-2'-deoxyguanosine (8-OHdG), thiol groups and the plasma activity of glutathione peroxidase were measured. A significant association between variant *TC+CC genotype and risk of overall testicular GCT, as well as seminoma development, was found. Moreover, carriers of variant *TT genotype were at almost 3-fold increased risk of seminoma development. Interestingly, combined *TT/*TC+CC genotype conferred a 7-fold higher risk for testicular GCT development. Finally, variant *AC+CC genotype was associated with a higher risk for the development of advanced diseased. The presence of assessed genetic variants was not associated with significantly higher levels of redox biomarkers in both testicular GCT patients, as well as in those diagnosed with seminoma. In conclusion, the polymorphic expression of certain antioxidant enzymes might affect susceptibility toward testicular GCT development, as well as the progression of the disease.
为了评估氧化还原生物标志物以及编码调节和催化抗氧化蛋白的多态性在睾丸生殖细胞肿瘤(GCT)发生发展及疾病进展中的潜在作用,我们对其进行了同步分析。在88例睾丸GCT患者(52例精原细胞瘤患者)和88例年龄匹配的对照中评估了(rs6721961)、(rs1332018)、(rs4880)和(rs8177412)多态性。检测了血浆中8-羟基-2'-脱氧鸟苷(8-OHdG)、巯基水平以及谷胱甘肽过氧化物酶的血浆活性。发现*TC + CC变异基因型与总体睾丸GCT风险以及精原细胞瘤发生之间存在显著关联。此外,*TT变异基因型携带者患精原细胞瘤的风险几乎增加了3倍。有趣的是,*TT/*TC + CC联合基因型使睾丸GCT发生风险增加7倍。最后,*AC + CC变异基因型与晚期疾病发生的较高风险相关。在睾丸GCT患者以及被诊断为精原细胞瘤的患者中,所评估的基因变异的存在与氧化还原生物标志物水平显著升高无关。总之,某些抗氧化酶的多态性表达可能会影响对睾丸GCT发生的易感性以及疾病的进展。