GSTP1 rs1138272 Polymorphism Affects Prostate Cancer Risk

Considering the pleiotropic roles of glutathione transferase (GST) omega class members in redox homeostasis, we hypothesized that polymorphisms in GSTO1 and GSTO2 might contribute to prostate cancer (PC) development and progression. Therefore, we performed a comprehensive analysis of GSTO1 and GSTO2 SNPs’ role in susceptibility to PC, as well as whether they might serve as prognostic biomarkers independently or in conjunction with other common GST polymorphisms (GSTM1, GSTT1, and GSTP1). Genotyping was performed in 237 PC cases and 236 age-matched controls by multiplex PCR for deletion of GST polymorphisms and quantitative PCR for SNPs. The results of this study, for the first time, demonstrated that homozygous carriers of both GSTO1*A/A and GSTO2*G/G variant genotypes are at increased risk of PC. This was further confirmed by haplotype analysis, which showed that H2 comprising both GSTO1*A and GSTO2*G variant alleles represented a high-risk combination. However, the prognostic relevance of polymorphisms in GST omega genes was not found in our cohort of PC patients. Analysis of the role of other investigated GST polymorphisms (GSTM1, GSTT1, and GSTP1) in terms of PC prognosis has shown shorter survival in carriers of GSTP1*T/T (rs1138272) genotype than in those carrying at least one referent allele. In addition, the presence of GSTP1*T/T genotype independently predicted a four-fold higher risk of overall mortality among PC patients. This study demonstrated a significant prognostic role of GST polymorphism in PC.

Section: Introductionmentioning

confidence: 99%

Polymorphisms in Genes Encoding Glutathione Transferase Pi and Glutathione Transferase Omega Influence Prostate Cancer Risk and Prognosis

Šantrić

Dragičević

Matić

et al. 2021

Front. Mol. Biosci.

Self Cite

“…In previous studies, Santric [31] reported a signi cant association between GSTP1 Ile105Val polymorphism and oxaliplatin-related toxicity. Kudhair [32] analyzed Arab populations and revealed that carrying GSTP1 Ile105Val substitution is positively correlated with a higher risk for lung cancer in WP tobacco smokers.…”

Section: Discussionmentioning

confidence: 90%

Predictive value of clinical toxicities of chemotherapy with fluoropyrimidines and oxaliplatin in colorectal cancer by DPYD and GSTP1 gene polymorphisms

Hou

et al. 2020

Preprint

Background: Fluoropyrimidines and platinum are still widely used for colorectal cancer (CRC) management. Several studies have reported that mutations of dihydropyrimidine dehydrogenase (DPYD) and glutathione S-transferase pi-1 (GSTP1) polymorphisms are related to Chemotherapy-related adverse events. In the present study, we purposed to assess the impact of DPYD and GSTP1 variants on the toxicity of adjuvant chemotherapy risk among the Hakka population, minimize adverse events, and to maximize therapy outcome for individualized treatment.Methods: Genotyping was examined in 104 patients diagnosed with CRC cases and receiving fluoropyrimidine and platinum drugs based chemotherapy regimen by direct sequencing of DPYD and GSTP1 polymorphisms. Three DPYD variants including *2A, *5A, *9A, and GSTP1 c.313A>G were analyzed and clinical outcomes were assessed.Results: The data suggest that the incidence of DPYD*5A, DPYD*9A, and GSTP1 c.313A>G variants were 38.4%, 24%, and 32.7%, respectively. DPYD*2A variant was not found. A total of 23 patients (22.1%) suffered severe vomiting and 19 patients (18.3%) suffered severe anemia. DPYD*5A polymorphism was found significantly associated with grade 3/4 ulceration (p = 0.001). GSTP1 was determined to be an independent risk factor for severe vomiting and skin ulceration (p = 0.042 and p = 0.018, respectively). Patients with GSTP1 c. 313A>G mutant type contributed to a higher risk for grade severe toxicity compared with wild genotype (p = 0.027). Nevertheless, no significant difference was found between patients with DPYD*2A, *5A, *9A for chemotherapeutic toxicity.Conclusions: The results demonstrated that GSTP1 polymorphisms were useful predictors of severe events. Screening of single nucleotide polymorphisms of GSTP1 in colorectal cancer patients before chemotherapy may help to realize personalized therapy.

“…In previous studies, Santric [25] reported a signi cant association between GSTP1 Ile105Val polymorphism and oxaliplatin-related toxicity. Kudhair [26] analyzed in Arab populations and revealed that carrying GSTP1 Ile105Val substitution is positively correlated with a higher risk for lung cancer in WP tobacco smokers.…”

Section: Discussionmentioning

confidence: 90%

Predictive value of clinical toxicities of chemotherapy with fluoropyrimidines and oxaliplatin in colorectal cancer by DPYD and GSTP1 gene polymorphisms

Hou

et al. 2020

Preprint

Background: Fluoropyrimidines and platinum are still widely used for colorectal cancer (CRC) management. Several studies have reported that mutations of dihydropyrimidine dehydrogenase (DPYD) and glutathione S-transferase pi-1 (GSTP1) polymorphisms are related to Chemotherapy-related adverse events. In the present study, we purposed to assess the impact of DPYD and GSTP1 variants on toxicity of chemotherapy risk among the Hakka population, minimize adverse events, and to maximize therapy outcome for individualized treatment.Methods: Genotyping was examined in 104 patients diagnosed with CRC cases and receiving fluoropyrimidine and platinum drugs based chemotherapy regimen by direct sequencing of DPYD and GSTP1 polymorphisms. Three DPYD variants including *2A, *5A, *9A, and GSTP1 c.313A>G were analyzed and clinical outcomes were assessed. Results: The data suggest that the incidence of DPYD*5A, DPYD*9A, and GSTP1 c.313A>G variants were 37.5%, 24%, and 31.7%, respectively. DPYD*2A variant was not found. A total of 38 patients (36.5%) suffered severe neutropenia and 23 patients (22.1%) suffered severe vomiting. DPYD*5A polymorphism was found significantly associated with grade 3/4 ulceration (p = 0.001). GSTP1 was determined to be an independent risk factor for severe neutropenia and ulceration (p = 0.010 and p = 0.034, respectively). Patients with GSTP1 c. 313A>G wild type contributed to a higher risk for grade severe toxicity compared with A/G + G/G genotype (p = 0.024). Nevertheless, no significant difference was found between patients with DPYD*9A T/T and T/C + C/C genotype for chemotherapeutic toxicity.Conclusions: The results demonstrated that DPYD*5A and GSTP1 polymorphisms were useful predictors of severe events. Screening of single nucleotide polymorphisms of DPYD and GSTP1 in colorectal cancer patients prior to chemotherapy may help to realize personalized therapy.