Glutathione S-transferases: an overview in cancer research

Pietro, Giuliano Di; Magno, Luiz Alexandre V.; Rios-Santos, Fabrício

doi:10.1517/17425250903427980

Cited by 205 publications

(170 citation statements)

References 108 publications

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“…2,[12][13][14] Body weight and body surface area have been also shown to contribute to PK variability. [15][16][17][18][19] Nevertheless, a large proportion of BU variability remains unexplained 20 and could be due to GST polymorphisms influencing GST activity [21][22][23][24][25] (Table 1). Although some studies have shown that GSTA1 genotypes influence the PK of oral and i.v.…”

Section: Introductionmentioning

confidence: 99%

Glutathione S-transferase gene variations influence BU pharmacokinetics and outcome of hematopoietic SCT in pediatric patients

Ansari

Rezgui

Théôret

et al. 2013

Bone Marrow Transplant

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on behalf of the Pediatric Disease Working Parties of the European Blood and Marrow Transplant Group BU is a key compound of conditioning regimens in children undergoing hematopoietic SCT (HSCT). Inter-individual differences in BU pharmacokinetics (PKs) might affect BU efficacy and toxicity. As BU is mainly metabolized by glutathione S-transferase (GST), we investigated the relationship between GSTA1, GSTM1 and GSTP1 genotypes with first-dose BU PKs, and the relationship with HSCT outcomes in 69 children receiving myeloablative conditioning regimen. GSTM1 null genotype correlated with higher BU exposure and lower clearance in patients older than 4 years (Pp0.04). In accordance with the suggested functional role, GSTA1*A2 haplotype was associated with lower drug levels and higher drug clearance (Pp0.03). Gene-dosage effect was also observed (Pp0.007). GSTA1 haplotypes were associated with HSCT outcomes. Patients with two copies of haplotype *A2 had better event free survival (P ¼ 0.03). In contrast, homozygous individuals for haplotypes *B and *B1 had higher occurrence of veno-occlusive disease (P ¼ 0.009). GSTM1 null individuals older than 4 years had more frequently graft versus host disease (P ¼ 0.03). In conclusion, we showed that GST gene variants influence BU PK and outcomes of HSCT in children. A model for the dosage adjustment with the inclusion of genetic and non-genetic factors should be evaluated in a future prospective validation cohort.

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Section: Introductionmentioning

confidence: 99%

Glutathione S-transferase gene variations influence BU pharmacokinetics and outcome of hematopoietic SCT in pediatric patients

Ansari

Rezgui

Théôret

et al. 2013

Bone Marrow Transplant

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“…It has been shown that Asians and Caucasians display higher frequencies of GSTM1-null genotypes than African populations (Di Pietro et al, 2010). The prevalence of the GSTT1-null genotype is low in Caucasians, and it is significantly greater in Asian populations.…”

Section: Discussionmentioning

confidence: 99%

“…Compared with GSTT1 and GSTM1 genetic polymorphisms (Bartsch et al,1998;Liu et al, 2000;Duell et al, 2002;Jiao et al, 2007;Vrana et al, 2009;Jang et al, 2012), very few studies have studied GSTP1 genetic polymorphisms and their associations with pancreatic cancer risk. Only one previous study reported that GSTP1 polymorphisms were significantly associated with pancreatic cancer survival (Jiao et al, 2007) Because the frequencies of GST genotypes vary across populations and ethnicities (Di Pietro et al, 2010), large inter-individual differences might exist in the metabolic response to carcinogen exposure. As a result, the risk of pancreatic cancer could be partly determined by these factors.…”

Section: Introductionmentioning

confidence: 99%

Lack of Associations between Genetic Polymorphisms in GSTM1, GSTT1 and GSTP1 and Pancreatic Cancer Risk: A Multi-Institutional Case-Control Study in Japan

Yamada

Ozaka²,

Inoue³

et al. 2014

Asian Pacific Journal of Cancer Prevention

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Background: We aimed to evaluate the role of genetic polymorphisms in tobacco carcinogen-metabolizing genes and their interactions with smoking in a hospital-based case-control study of Japanese subjects. Materials and Methods: We examine the associations of pancreatic cancer risk with genetic polymorphisms in GSTM1, GSTT1 and GSTP1, phase II enzymes that catalyze the conjugation of toxic and carcinogenic electrophilic molecules. The study population consisted of 360 patients and 400 control subjects, who were recruited from several medical facilities in Japan. Unconditional logistic regression methods were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the associations between genotypes and pancreatic cancer risk. Results: Among the control subjects, the prevalence of the GSTM1-null genotype and the GSTT1-null genotype was approximately 56% and 48%, respectively. Cases and controls were comparable in terms of GSTM1 and GSTT1 genotype distributions. Neither of the deleted polymorphisms in GSTM1 and GSTT1 was associated with the risk of pancreatic cancer, with an age-and sex-adjusted OR of 0.99 (95%CI: 0.74-1.32) for the GSTM1-null genotype, and 0.98 (95%CI: 0.73-1.31) for the GSTT1-null genotype. The OR was 0.97 (95%CI: 0.64-1.47) for individuals with the GSTM1 and GSTT1-null genotypes compared with those with the GSTM1 and GSTT1-present genotypes. No synergistic effects of smoking or GST genotypes were observed. Conclusions: Our results indicate no overall association between the GSTM1 and GSTT1 deletion polymorphisms and pancreatic cancer risk in the Japanese subjects in our study.

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“…It has been shown that polymorphic expression of GSTs is associated with the altered xenobiotics detoxification efficiency, thus influencing an individual's susceptibility to carcinogens and various diseases (Di Pietro et al 2010;Suvakov et al 2013;Eslami and Sahebkar 2014;Kim et al 2015). Still, there are no data regarding the association between GST genetic polymorphism and bladder cancer risk, neither in patients with BEN, nor in individuals who originate from BEN regions.…”

Section: Introductionmentioning

confidence: 99%

Common Polymorphisms in GSTA1, GSTM1 and GSTT1 Are Associated with Susceptibility to Urinary Bladder Cancer in Individuals from Balkan Endemic Nephropathy Areas of Serbia

Matić

Dragićević²,

Pekmezović

et al. 2016

Tohoku J. Exp. Med.

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Balkan endemic nephropathy (BEN) is a chronic familial form of interstitial nephritis that might eventually lead to end stage renal disease. This nephropathy affects individuals living along of the Danube River and its tributaries in Serbia, Bosnia, Croatia, Bulgaria and Romania. The increased incidence of urinary tract tumors in the BEN areas is well described, but its specific genetic predisposition is still unclear. Certain nephrocarcinogenic compounds, including those associated with BEN, are metabolized by glutathione S-transferase (GST) superfamily of phase II detoxication enzymes. Importantly, the GST-mediated detoxification may result in formation of more toxic compounds. We examined the association of common GST polymorphisms and bladder cancer (BC) risk in individuals from BEN areas in Serbia. A hospitalbased case-control study included 201 BC cases (67 from BEN region) and 122 controls. Each polymorphism was identified by a PCR-based method. Individuals from BEN region with low-expression GSTA1 genotype (AB+BB) exhibited a 2.6-fold higher BC risk compared to those with GSTA1 (AA) genotype who were from non-BEN region (OR = 2.60, p = 0.015). In contrast, carriers of GSTM1-active genotype from BEN region had a 2.9-fold increased BC risk compared to those with GSTM1-active genotype from non-BEN region (OR = 2.90, p = 0.010). Likewise, carriers with GSTT1-active genotype from BEN region exhibited 2.1-fold higher BC risk compared to those from non-BEN region with GSTT1-active genotype (OR = 2.10, p = 0.027). Thus, common polymorphisms in GSTA1, GSTM1 and GSTT1 are associated with susceptibility to BC in individuals from BEN areas of Serbia.

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Glutathione S-transferases: an overview in cancer research

Abstract: Although polygenic factors are involved in increased risk of cancer, the interindividual GST variability plays a central role in reduce cells exposure to carcinogens.

Cited by 205 publications

References 108 publications

Glutathione S-transferase gene variations influence BU pharmacokinetics and outcome of hematopoietic SCT in pediatric patients

Glutathione S-transferase gene variations influence BU pharmacokinetics and outcome of hematopoietic SCT in pediatric patients

Lack of Associations between Genetic Polymorphisms in GSTM1, GSTT1 and GSTP1 and Pancreatic Cancer Risk: A Multi-Institutional Case-Control Study in Japan

Common Polymorphisms in<i> GSTA1</i>, <i>GSTM1</i> and <i>GSTT1 </i>Are Associated with Susceptibility to Urinary Bladder Cancer in Individuals from Balkan Endemic Nephropathy Areas of Serbia

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