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GSTT1, GSTP1, and GSTM1 genetic variants are associated with survival in previously untreated metastatic breast cancer.

ABSTRACT: The polymorphisms in genes including GSTM1, GSTP1 and GSTT1 have been found to predict development and therapeutic efficacy in various malignancies. Breast cancer is one of most common cancers among women. In this study, we evaluated the prognostic value of three functional polymorphisms of GSTs in patients with previously untreated metastatic breast cancer (MBC).The genotype of GSTT1, GSTP1, and GSTM1 in 170 patients with previously untreated MBC from one single center were assessed via PCR-based RFLP methods. The prognostic of polymorphisms on overall survival (OS) was examined using the Kaplan-Meier estimates and Cox proportional hazard ratio (HR) regression analyses.The null genotypes of GSTT1 and GSTM1 were significantly correlated to poor OS compared with the present genotypes, respectively. After adjusting for clinic-pathologic factors, GSTT1 and GSTM1 genetic variants were still significantly associated with OS (HR, 1.92; 95% CI, 1.26-2.91 and HR, 1.53; 95% CI, 1.05-2.23). GSTT1 and GSTM1 were independent survival predictors and GSTP1 was not associated with overall survival of previous untreated MBC.This exploratory analysis suggests that in addition to clinic-pathologic factors, the genetic variants in GSTT1 and GSTM1 might be predictive of survival outcome in patients with previously untreated MBC.

SUBMITTER: Zhang J

PROVIDER: S-EPMC5739688 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature

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GSTT1, GSTP1, and GSTM1 genetic variants are associated with survival in previously untreated metastatic breast cancer.

Zhang Jian J Wu Ying Y Hu Xichun X Wang Biyun B Wang Leiping L Zhang Sheng S Cao Jun J Wang Zhonghua Z

Oncotarget 20171114 62

<h4>Purpose</h4>The polymorphisms in genes including GSTM1, GSTP1 and GSTT1 have been found to predict development and therapeutic efficacy in various malignancies. Breast cancer is one of most common cancers among women. In this study, we evaluated the prognostic value of three functional polymorphisms of GSTs in patients with previously untreated metastatic breast cancer (MBC).<h4>Patients and methods</h4>The genotype of GSTT1, GSTP1, and GSTM1 in 170 patients with previously untreated MBC fro ...[more]

PMID: 29285301

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Project description:Background and objectivesThe GSTM1, GSTT1 and GSTP1 polymorphisms might be involved in inactivation of procarcinogens that contribute to the genesis and progression of cancers. However, studies investigating the association between GSTM1, GSTT1 or GSTP1 polymorphisms and prostate cancer (PCa) risk report conflicting results, therefore, we conducted a meta-analysis to re-examine the controversy.MethodsPublished literature from PubMed, Embase, Google Scholar and China National Knowledge Infrastructure (CNKI) were searched (updated to June 2, 2012). According to our inclusion criteria, studies that observed the association between GSTM1, GSTT1 or GSTP1 polymorphisms and PCa risk were included. The principal outcome measure was the odds ratio (OR) with 95% confidence interval (CI) for the risk of PCa associated with GSTM1, GSTT1 and GSTP1 polymorphisms.ResultsFifty-seven studies involving 11313 cases and 12934 controls were recruited. The overall OR, which was 1.2854 (95% CI = 1.1405-1.4487), revealed a significant risk of PCa and GSTM1 null genotype, and the similar results were observed when stratified by ethnicity and control source. Further, the more important is that the present study first reported the high risks of PCa for people who with dual null genotype of GSTM1 and GSTT1 (OR = 1.4353, 95% CI = 1.0345-1.9913), or who with GSTT1 null genotype and GSTP1 A131G polymorphism (OR = 1.7335, 95% CI = 1.1067-2.7152). But no association was determined between GSTT1 null genotype (OR = 1.102, 95% CI = 0.9596-1.2655) or GSTP1 A131G polymorphism (OR = 1.0845, 95% CI = 0.96-1.2251) and the PCa risk.ConclusionsOur meta-analysis suggested that the people with GSTM1 null genotype, with dual null genotype of GSTM1 and GSTT1, or with GSTT1 null genotype and GSTP1 A131G polymorphism are associated with high risks of PCa, but no association was found between GSTT1 null genotype or GSTP1 A131G polymorphism and the risk of PCa. Further rigorous analytical studies are highly expected to confirm our conclusions and assess gene-environment interactions with PCa risk.

Project description:Occupational exposure to benzene has been associated with leukemia, anemia, leukopenia, and thrombocytopenia. Genetic susceptibility to benzene toxicity in humans may be related to variations in benzene metabolizing genes. The main objective of this study was to ascertain whether polymorphism of GSTP1, GSTM1, GSTT1 and CYP2E1 genes might influence susceptibility to the adverse effects of benzene among employees of a petrochemical plant. In this cross-sectional study, 124 employees of a petrochemical plant who had been occupationally exposed to benzene and had one or more abnormal hematological parameter (cases) and 184 subjects with a similar exposure scenario, free from any abnormal hematological parameters (referent) were studied. Atmospheric concentrations of benzene were measured and GSTM1 and GSTT1 genotypes were evaluated using the multiplex polymerase chain reaction (PCR) technique. Additionally, GSTP1 and CYP2E1 genotypes were determined by PCR- restriction fragment length polymorphism (PCR-RFLP). The frequency of null GSTT1 genotype in cases was significantly higher than that of referent group (32.3 vs. 18.5%, OR 2.1, 95% CI 1.23-3.56, p = 0.004). The mean value of platelets in subjects with null GSTT1 genotype was significantly lower than that of individuals with positive GSTT1 genotype (p = 0.015). Conversely, the mean value of leukocytes was significantly higher in subjects with null GSTM1 genotype as compared to those with positive GSTM1 genotype (p = 0.026). Logistic regression analysis showed that, subjects with null GSTT1 genotype had a significantly higher risk for hematological disorders, as compared to those with positive GSTT1 genotype (OR 2.1, 95% CI 1.23-3.56). Moreover, subjects with both null GSTT1 and GSTM1 genotypes had a significantly higher risk for hematological disorders as compared to subjects with positive GSTT1 and GSTM1 genotypes (OR 2.35, 95% CI 1.14-4.8). The results of this study showed that, individuals carrying null GSTT1 or both null STT1 and GSTM1 genotypes had a higher risk and were more susceptible to benzene-induced hematological disorders.

Project description:BackgroundCoronary artery disease (CAD) is a multifactorial disease that may be caused by the interaction between environmental and genetic risk factors. Glutathione S-transferases (GSTs) are known to participate in detoxification and metabolism of a wide range of xenobiotic compounds and oxidative stress products. Considering the interaction between environmental and genetic factors in CAD, we investigated the genetic polymorphisms of GSTM1, GSTT1, and GSTP1 in the Iranian population.Patients and methodsTwo hundred and forty-four CAD cases and 281 healthy controls were studied. The genotype of GSTM1, GSTT1, and GSTP1 genes was determined by multiplex polymerase chain reaction (PCR) and PCR-restriction fragment length polymorphism (PCR-RFLP) techniques. Multivariable logistic regression analysis was used to calculate the odds ratios (ORs) and 95% confidence intervals (CI). Multifactor dimensionality reduction (MDR) analysis was also carried out to analyze the gene-gene and gene-environment interaction.ResultsThe genotype and allele distribution of the three variations were not significantly different between CAD patients and controls (p > 0.05). The subgroup analysis revealed no significant gene-gene interactions or gene-gene combination effects linked to CAD susceptibility. However, MDR analysis selected the GSTM, GSTT pairwise and three genes combination models associated with the susceptibility to CAD. In addition, its result revealed that smoking in combination with GSTM1 (two-way) and GSTT, GSTP (three-way) genes might increase the risk of CAD. Furthermore, a significant interaction between GSTT1-null polymorphism and dyslipidemia was found in multivariable logistic regression analyses in the gene-environmental interactions on CAD risk.ConclusionOur results suggest that the GSTM1, GSTT1 and GSTP1 genetic variations are not directly associated with the susceptibility to CAD in Iranian patients. Due to MDR results, there might be a non-linear association between interactions of two or three genes and smoking with CAD. There is also an association between CAD risk factors and GST variations, which requires supplementary confirmation with larger sample sizes.

Dataset Information

GSTT1, GSTP1, and GSTM1 genetic variants are associated with survival in previously untreated metastatic breast cancer.

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GSTT1, GSTP1, and GSTM1 genetic variants are associated with survival in previously untreated metastatic breast cancer.

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