GSTM1-null and GSTA1-low activity genotypes are associated with enhanced oxidative damage in bladder cancer

Savić-Radojević, Ana; Djukić, Tatjana; Simić, Tatjana; Plješa-Ercegovac, Marija; Dragičević, Dejan; Pekmezović, Tatjana; Cekerevac, Milica; Šantrić, Veljko; Matić, Marija

doi:10.1179/1351000212y.0000000031

Cited by 21 publications

(8 citation statements)

References 27 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In the study of oxidative DNA modifications among malignant diseases, 8-OHdG seems to be the most appropriate biomarker. Indeed, bladder cancer patients, carriers of GSTM1-null and GSTA1variant genotypes, exhibited higher urinary 8-OHdG levels (Savic-Radojevic et al 2013). In this line, our results on the higher levels of 8-OHdG, a biomarker of free radicalinduced DNA-oxidative damage, among ccRCC patients with GSTO2*G/G variant genotype (rs2297235) seem plau-sible.…”

Section: Controls N (%) Patients N (%) or (95% Ci) A Psupporting

confidence: 74%

Concomitance of Polymorphisms in Glutathione Transferase Omega Genes Is Associated with Risk of Clear Cell Renal Cell Carcinoma

Radić

Ćorić

Plješa-Ercegovac

et al. 2018

Tohoku J. Exp. Med.

View full text Add to dashboard Cite

Glutathione S-transferases (GSTs), a superfamily of multifunctional enzymes, play an important role in the onset and progression of renal cell carcinoma (RCC). However, novel GST omega class (GSTO), consisting of GSTO1-1 and GSTO2-2 isoenzymes, has not been studied in RCC yet. Two coding single nucleotide polymorphisms (SNPs) supposedly affect their functions: GSTO1*C419A (rs4925) causing alanine to aspartate substitution (*A140D) and GSTO2*A424G (rs156697) causing asparagine to aspartate substitution (*N142D), and have been associated with several neurodegenerative diseases and cancers. Functional relevance of yet another GSTO2 polymorphism, identified at the 5' untranslated (5'UTR) gene region (GSTO2*A183G, rs2297235), has not been clearly discerned so far. Therefore, we aimed to assess the effect of specific GSTO1 and GSTO2 gene variants, independently and in interaction with established risk factors (smoking, obesity and hypertension) on the risk for the most aggressive RCC subtype, the clear cell RCC (ccRCC). Genotyping was performed in 239 ccRCC patients and 350 matched controls, while plasma levels of 8-hydroxy-2'-deoxyguanosine (8-OHdG), a biomarker of oxidative DNA damage, were determined by ELISA. As a result, combined effect of all three variant genotypes exhibited almost 3-fold risk of RCC development. Additionally, this association was confirmed at the haplotype level [variant GSTO1*A/GSTO2*G (rs156697)/GSTO2*G (rs2297235) haplotype], suggesting a potential role of those variants in propensity to RCC. Regarding the gene-environment interactions, variant GSTO2*G (rs156697) homozygous smokers are at higher ccRCC risk. Association in terms of oxidative DNA damage was found for GSTO2 polymorphism in 5'UTR and 8-OHdG. In conclusion, the concomitance of GSTO polymorphisms may influence ccRCC risk.

show abstract

Section: Controls N (%) Patients N (%) or (95% Ci) A Psupporting

confidence: 74%

Concomitance of Polymorphisms in Glutathione Transferase Omega Genes Is Associated with Risk of Clear Cell Renal Cell Carcinoma

Radić

Ćorić

Plješa-Ercegovac

et al. 2018

Tohoku J. Exp. Med.

View full text Add to dashboard Cite

show abstract

“…8-OHdG levels have also been evaluated in patients with different types of cancer. [23][24][25][26][27][28][29][30][31][32][33][34][35][36][37] No differences in urinary 8-OHdG values are generally found between patients with lung cancer and control groups. [26][27][28] However, Çobanoğlu et al 29 reported high 8-OHdG values in patients with cancer, and Yamamoto et al 23 reported significantly higher urinary 8-OHdG levels in patients with gynecological cancers compared to those in controls.…”

Section: Discussionmentioning

confidence: 99%

Measuring Oxidative DNA Damage With 8-Hydroxy-2’-Deoxyguanosine Levels in Patients With Laryngeal Cancer

Mazlumoglu¹,

Özkan

Hakan

et al. 2016

Ann Otol Rhinol Laryngol

View full text Add to dashboard Cite

show abstract

“…Eight isoforms of cytosolic-soluble GSTs have been recognized in humans, including α, κ, μ, π, σ, θ, ζ, and ω 3,4 . Glutathione S-transferase α1 (GSTA1, Gene ID: 2938) has shown both stimulatory [5][6][7][8] and inhibitory effects [9][10][11][12] on tumorigenesis. The association between genetic polymorphism of GSTA1 and susceptibility to cancer has been discussed in previous studies [13][14][15] , but…”

Section: Introductionmentioning

confidence: 99%

Glutathione S-transferase A1 suppresses tumor progression and indicates better prognosis of human primary hepatocellular carcinoma

Liu¹,

Sui²,

Zhang³

et al. 2020

J. Cancer

View full text Add to dashboard Cite

Glutathione S-transferase (GST) family members play an important role in detoxification, metabolism and carcinogenesis. The aim of this study is to investigate the effect of Glutathione S-transferase A1 (GSTA1) on the prognosis of HCC and to understand its role in tumor progression and the possible mechanism. GSTA1 in HCC was assessed using immunohistochemical staining, and it was found that HCC patients with better pathological differentiation had higher GSTA1 abundance. Further, high GSTA1 expression was correlated with low AFP, absent PVTT, and early stage TNM for HCC patients. Higher GSTA1 indicated longer overall survival and disease-free survival, while lower GSTA1 indicated poorer prognosis. Subsequently, lentiviral vector carrying GSTA1 gene was successfully constructed and maintained high expression in 97H and SNU449 liver cancer cells. We found that high GSTA1 restrained liver cancer cell proliferation, migration and invasion in vitro. Western blot showed that LKB1 and p-AMPK were upregulated while p-mTOR, p-p70 S6 Kinase and MMP-9 were downregulated in high GSTA1 groups. Taken together, high GSTA1 correlated with satisfactory prognosis of HCC. Additionally, GSTA1 may act as a protective factor through suppression of tumorigenesis by targeting AMPK/mTOR in HCC.

show abstract

GSTM1-null and GSTA1-low activity genotypes are associated with enhanced oxidative damage in bladder cancer

Abstract: Our results suggest that absent GSTM1 or reduced GSTA1 antioxidant activity may increase the accumulation of oxidative DNA damage, thereby contributing to the malignant potential of TCC.

Cited by 21 publications

References 27 publications

Concomitance of Polymorphisms in Glutathione Transferase Omega Genes Is Associated with Risk of Clear Cell Renal Cell Carcinoma

Concomitance of Polymorphisms in Glutathione Transferase Omega Genes Is Associated with Risk of Clear Cell Renal Cell Carcinoma

Measuring Oxidative DNA Damage With 8-Hydroxy-2’-Deoxyguanosine Levels in Patients With Laryngeal Cancer

Glutathione S-transferase A1 suppresses tumor progression and indicates better prognosis of human primary hepatocellular carcinoma

Contact Info

Product

Resources

About