Associations of the glutathione S-transferase P1 Ile105Val genetic polymorphism with gynecological cancer susceptibility: a meta-analysis.
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ABSTRACT:
SUBMITTER: Zhao E
PROVIDER: S-EPMC5522203 | biostudies-other | 2017 Jun
REPOSITORIES: biostudies-other
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Project description:It is well established that type 2 diabetes mellitus (T2DM) is associated with oxidative stress and glutathione S-transferases (GSTs) protect cells against oxidative stress. The missense substitution Ile105Val (rs1695) of the glutathione S-transferase P1 (GSTP1, OMIM: 134660) results from an A/G base substitution at nucleotide 313. Many studies have evaluated the correlation between the rs1695 polymorphism and T2DM, but the results remain inconclusive. The aim of the present meta-analysis was to investigate the association between GSTP1 Ile105Val polymorphism and the susceptibility risk of T2DM. Eligible studies (published before August 2017) were identified in several databases. The heterogeneity between studies was evaluated with the chi-square based Q test and the I2 test. The strengths of the association were assessed by pooled odds ratios (ORs) and the corresponding 95 % confidence interval (95 % CI) using either a fixed or random-effects models. Eighteen studies documenting a total of 2595 T2DM cases and 2888 controls were included in this meta-analysis. In the overall analysis there was no significant association between the rs1695 polymorphism and the risk of T2DM. The subgroup analyses stratified by ethnicity, publication year and sample size did not reveal significant association between the study polymorphism and the risk of T2DM and any sources contributing to the substantial heterogeneity between studies. The present meta-analysis suggested that there was significant heterogeneity between studies. Considering some limi tations of our meta-analysis, further large-scale studies should be done to reach a more comprehensive understanding.
| S-EPMC5735339 | biostudies-literature
Project description:BackgroundSeveral studies concerning the association between glutathione S-transferase P1 (GSTP1) Ile105Val polymorphism and male infertility risk have reported controversial findings. The present study was aimed to explore this association using a meta-analysis.MethodsThe PubMed, EMBASE, China National Knowledge Infrastructure (CNKI), and Wanfang databases were searched. Odds ratios (OR s) with 95% confidence intervals (CI s) were calculated to estimate the strength of the association.ResultsA total of 3282 cases and 3268 controls in nine case-control studies were included. There was no significant association between GSTP1 Ile105Val polymorphism and male infertility in the overall population, but significant associations were found under the dominant (OR = 1.23, 95% CI = 1.04-1.46, I2 = 32.2%) and heterozygote (OR = 1.29, 95% CI = 1.08-1.53, I2 = 26.8%) models after excluding studies for which the data did not satisfy Hardy-Weinberg equilibrium (HWE). Similarly, subgroup analyses revealed no significant association in Asians or Chinese population although a significant association was apparent among Chinese population in studies with HWE under the heterozygote model (OR = 1.25, 95% CI = 1.03-1.52, I2 = 44.1%). Significant heterogeneity could be observed in some genetic models, but this heterogeneity was not significant when stratified by HWE. No evidence for publication bias was found.ConclusionsThe GSTP1 Ile105Val polymorphism might not be associated with male infertility risk, and thus additional well-designed studies with larger sample size are warranted.
| S-EPMC5407046 | biostudies-literature
Project description:BackgroundGSTP1, which is one major group of the glutathione S-transferase family, plays an important role in the metabolism of carcinogens and toxins, reducing damage of DNA as a suppressor of carcinogenesis. The 341C>T polymorphism of the GSTP1 has been implicated in cancer risk through cutting down its metabolic detoxification activities. However, results from previous studies remain conflicting rather than conclusive. To clarify the correlation and provide more statistical evidence for detecting the significance of 341C>T, a meta-analysis was conducted.Methodology/principal findingsThe relevant studies were identified through searching of PubMed, Embase, ISI Web of Knowledge and China National Knowledge Infrastructure in August 2012, and selected based on the established inclusion criteria for publications, then a meta-analysis was performed to quantitatively summarize the association of GSTP1 341C>T polymorphism with cancer susceptibility. Stratified analyses were employed to identify the source of heterogeneity. Publication bias was evaluated as well as sensitivity analysis. Based on 28 case-control studies with 13249 cases and 16798 controls, the pooled results indicated that the variant genotypes significantly increased the risk of cancer in homozygote comparison (TT versus CC: P = 0.012, OR = 1.40, 95% CI: 1.08-1.81, P(het.) = 0.575), and recessive model (TT versus CT/CC: P = 0.012, OR = 1.40, 95% CI: 1.08-1.81, P(het.) = 0.562). This was confirmed when stratified analyses were conducted according to ethnicity, source of control, matched control, quality score and cancer types. Moreover, significantly increased risk of cancer was also found in lung cancer (heterozygote comparison and dominant model). The stability of these observations was confirmed by a sensitivity analysis. Begger's funnel plot and Egger's test did not reveal any publication bias.Conclusions/significanceThis meta-analysis suggests that the GSTP1 341C>T polymorphism may contribute to genetic susceptibility to cancer, especially to lung cancer, and in Asian population. Nevertheless, additional well-designed studies focusing on different ethnicity and cancer types are needed to provide a more exact and comprehensive conclusion.
| S-EPMC3578943 | biostudies-literature
Project description:ObjectivesTo investigate the correlation between glutathione S-transferase P1 (GSTP1) Ile105Val polymorphism and colorectal cancer (CRC) risk.MethodsStudies were identified to investigate the association between GSTP1 Ile105Val polymorphism and CRC risk. Systematic computerized searches of the PubMed, Chinese National Knowledge Infrastructure, WANFANG and SinoMed were performed. Summary odds ratios (OR) and 95% confidence intervals (95% CI) were used to measure GSTP1 Ile105Val polymorphisms and CRC risk.ResultsA total of 23 retrospective studies were included in the meta-analysis. During all studies including 6,981 cases and 8,977 controls, sample sizes ranged from 146 to 2,144. Overall, the pooled results revealed that Ile105Val polymorphism was not associated with CRC risk and confused results were found in subgroup analyses. Further meta-analyses were conducted after excluding low-quality studies. GSTP1 Ile105Val is associated with increased risk of CRC limited in studies with matched control. There was no significant heterogeneity in all genetic comparisons, but heterogeneity existed in subgroup analyses of heterozygous and dominant comparisons. The meta-regression analyses indicated that matched controls were the significant factor influencing between-study heterogeneity in all possible influential factors including published year, ethnicity, source of control, sample size, Hardy-Weinberg equilibrium (HWE) in control and matched controls. Sensitivity analysis revealed the pooled ORs were not changed before and after removal of each single study in all genetic comparisons, indicating the robustness of the results.ConclusionsGSTP1 Ile105Val might be associated with increased risk of CRC. However, more high-quality case-control studies should be performed to confirm the authenticity of our conclusion.
| S-EPMC4076718 | biostudies-literature
Project description:BackgroundWe conducted a meta-analysis to evaluate the relationship between the glutathione S-transferase μ1 (GSTM1)- and glutathione S-transferase θ1 (GSTT1)- null genotypes and susceptibility to bladder cancer.MethodsWe identified association reports from the databases of PubMed, Embase, the Cochrane Library and the China Biological Medicine Database (CBM disc) on July 1, 2017 and synthesized eligible investigations. Results were expressed using odds ratios (ORs) for dichotomous data, and we also calculated 95% confidence intervals (CIs).ResultsIn this meta-analysis, we found that the GSTM1-null genotype was associated with bladder cancer risk in the overall population, and individually in whites, Africans and Asians (overall population: OR = 1.40, 95% CI: 1.31-1.48, P<0.00001; whites: OR = 1.39, 95% CI: 1.26-1.54, P<0.00001; Africans: OR = 1.54, 95% CI: 1.16-2.05, P = 0.003; Asians: OR = 1.45, 95% CI: 1.33-1.59, P<0.00001). The GSTT1-null genotype was associated with bladder cancer risk in the overall population, but not in whites, in Africans or Asians (overall population: OR = 1.11, 95% CI: 1.01-1.22, P = 0.03; whites: OR = 1.16, 95% CI: 0.99-1.36, P = 0.07; Africans: OR = 1.07, 95% CI: 0.65-1.76, P = 0.79; Asians: OR = 1.05, 95% CI: 0.91-1.22, P = 0.51). Interestingly, a dual-null GSTM1-GSTT1 genotype was associated with bladder cancer risk in the overall population and in Asians (overall population: OR = 1.48, 95% CI: 1.15-1.92, P = 0.002; Asians: OR = 1.62, 95% CI: 1.15-2.28, P = 0.006). In conclusion, the GSTM1-null, GSTT1-null and dual-null GSTM1-GSTT1 genotypes might be associated with the onset of bladder cancer, but additional genetic-epidemiological studies should be conducted to explore this association further.
| S-EPMC6233535 | biostudies-literature
Project description:Disturbed redox balance in heart failure (HF) might contribute to impairment of cardiac function, by oxidative damage, or by regulation of cell signaling. The role of polymorphism in glutathione transferases (GSTs), involved both in antioxidant defense and in regulation of apoptotic signaling pathways in HF, has been proposed. We aimed to determine whether GST genotypes exhibit differential risk effects between coronary artery disease (CAD) and idiopathic dilated cardiomyopathy (IDC) in HF patients. GSTA1, GSTM1, GSTP1, and GSTT1 genotypes were determined in 194 HF patients (109 CAD, 85 IDC) and 274 age- and gender-matched controls. No significant association was found for GSTA1, GSTM1, and GSTT1 genotypes with HF occurrence due to either CAD or IDC. However, carriers of at least one variant GSTP1∗Val (rs1695) allele were at 1.7-fold increased HF risk than GSTP1∗Ile/Ile carriers (p = 0.031), which was higher when combined with the variant GSTA1∗B allele (OR = 2.2, p = 0.034). In HF patients stratified based on the underlying cause of disease, an even stronger association was observed in HF patients due to CAD, who were carriers of a combined GSTP1(rs1695)/GSTA1 "risk-associated" genotype (OR = 2.8, p = 0.033) or a combined GSTP1∗Ile/Val+Val/Val (rs1695)/GSTP1∗AlaVal+∗ValVal (rs1138272) genotype (OR = 2.1, p = 0.056). Moreover, these patients exhibited significantly decreased left ventricular end-systolic diameter compared to GSTA1∗AA/GSTP1∗IleIle carriers (p = 0.021). Higher values of ICAM-1 were found in carriers of the GSTP1∗IleVal+∗ValVal (rs1695) (p = 0.041) genotype, whereas higher TNFα was determined in carriers of the GSTP1∗AlaVal+∗ValVal genotype (rs1138272) (p = 0.041). In conclusion, GSTP1 polymorphic variants may determine individual susceptibility to oxidative stress, inflammation, and endothelial dysfunction in HF.
| S-EPMC6589253 | biostudies-literature
Project description:Background and objectivesStudies investigating the association between glutathione S-transferase M1 (GSTM1) gene polymorphism and laryngeal cancer risk have reported conflicting results. The aim of the present study was to conduct a meta-analysis assessing the possible associations of GSTM1 gene polymorphism with laryngeal cancer risk.MethodsThe relevant studies were identified through a search of PubMed, Embase, ISI Web of Knowledge and Chinese National Knowledge Infrastructure until May 2011 and selected on the basis of the established inclusion criteria for publications, then a meta-analysis was performed to quantitatively summarize association of GSTM1 polymorphism with laryngeal cancer susceptibility.ResultsSeventeen studies were included in the present meta-analysis (2,180 cases and 2,868 controls). The combined results based on all studies showed that GSTM1 null genotype was associated with increased laryngeal cancer risk (OR = 1.17, 95% CI = 1.04∼1.31). When stratifying for race, GSTM1 null genotype exhibited increased laryngeal cancer risk in Caucasians (OR = 1.15, 95% CI = 1.01∼1.31), while no significant association was detected in Asians (OR = 1.25, 95% CI = 0.80∼1.96). In the subgroup analysis based on source of controls, significant associations were observed in the population-based studies (OR = 1.15, 95% CI = 1.01∼1.31) yet not in the hospital-based studies (OR = 1.25, 95% CI = 0.93∼1.67). Furthermore, in the subgroup analysis based on sample size, significant associations were also found in studies with at least 50 cases and 50 controls (OR = 1.15, 95% CI = 1.02∼1.30) but not in studies with fewer than 50 cases or 50 controls (OR = 1.46, 95% CI = 0.87∼2.46).ConclusionsThis meta-analysis supported that the GSTM1 gene polymorphism was associated with laryngeal cancer, particularly in Caucasians, and these associations varied in different subgroup, which indicated that population-based study with larger sample size was more appropriate in design of future study.
| S-EPMC3416752 | biostudies-literature
Project description:Chemotherapy resistance of ovarian cancer, regarded as the most lethal malignant gynecological disease, can be explained by several mechanisms, including increased activity of efflux transporters leading to decreased intracellular drug accumulation, increased efflux of the therapeutic agents from the cell by multidrug-resistance-associated protein (MRP1), enhanced DNA repair, altered apoptotic pathways, silencing of a number of genes, as well as drug inactivation, especially by glutathione transferase P1 (GSTP1). Indeed, GSTP1 has been recognized as the major enzyme responsible for the conversion of drugs most commonly used to treat metastatic ovarian cancer into less effective forms. Furthermore, GSTP1 may even be responsible for chemoresistance of non-GST substrate drugs by mechanisms such as interaction with efflux transporters or different signaling molecules involved in regulation of apoptosis. Recently, microRNAs (miRNAs) have been identified as important gene regulators in ovarian cancer, which are able to target GST-mediated drug metabolism in order to regulate drug resistance. So far, miR-186 and miR-133b have been associated with reduced ovarian cancer drug resistance by silencing the expression of the drug-resistance-related proteins, GSTP1 and MDR1. Unfortunately, sometimes miRNAs might even enhance the drug resistance in ovarian cancer, as shown for miR-130b. Therefore, chemoresistance in ovarian cancer treatment represents a very complex process, but strategies that influence GSTP1 expression in ovarian cancer as a therapeutic target, as well as miRNAs affecting GSTP1 expression, seem to represent promising predictors of chemotherapeutic response in ovarian cancer, while at the same time represent potential targets to overcome chemoresistance in the future.
| S-EPMC9696103 | biostudies-literature
Project description:BackgroundSeveral case-control studies investigating the relationship between genetic polymorphisms of glutathione S-transferase (GST) M1, GSTT1, and GSTP1 (rs1695) and the risk of breast cancer have reported contradictory results. We therefore performed a meta-analysis to clarify this issue.Materials and methodsAn updated meta-analysis using PubMed and Web of Knowledge databases for the eligible case-control studies was performed. Random- or fixed-effects model was used.ResultsA total of 10,067 cancer cases and 12,276 controls in 41 independent case-control studies from 19 articles were included in this meta-analysis. Significant increase in risk of breast cancer for Asians was found in GSTM1-null genotype (P=0.012, odds ratio [OR] =1.17, 95% confidence interval [CI] =1.04-1.32) and GSTT1-null genotype (P=0.039, OR =1.19, 95% CI =1.01-1.41). In addition, our results showed that the GSTP1 (rs1695) polymorphisms can significantly increase the risk among Caucasians (P=0.042, OR =1.16, 95% CI =1.01-1.34). Sensitivity analysis and publication bias further confirmed the dependability of the results in this meta-analysis.ConclusionOur results demonstrate that both GSTM1- and GSTT1-null polymorphisms are associated with an increased risk of breast cancer in Asians and that GSTP1 Val105Ile (rs1695) polymorphism is associated with an increased breast cancer risk in Caucasians.
| S-EPMC4869650 | biostudies-literature
Project description:Background/aimsGlutathione S-transferase P1 (GSTP1) scavenges radicals via its peroxidase activity. The purpose of this study was to determine the association of GSTP1 genetic polymorphisms with the expression of H. pylori-associated gastroduodenal disease.MethodsThis study involved 1,911 subjects, comprising patients with four diseases (gastric cancer, dysplasia, benign gastric ulcer, and duodenal ulcer disease) and controls. Biallelic polymorphisms were genotyped by restriction fragment length polymorphism techniques.ResultsThe frequency of the genetic polymorphism at nucleotide 313 of GSTP1 did not differ among the five study groups. However, when the gastric cancer group was subdivided into advanced gastric cancer (AGC) and early gastric cancer, the frequency of the G/G genotype was significantly higher in the AGC group than in all the control subgroups (OR: 1.2, 95% CI: 1.1-4.9). The frequency of this genotype differed significantly in the H. pylori-positive AGC group (OR: 2.7, 95% CI: 1.1-6.3) but not in the H. pylori-negative group. Furthermore, the difference was greater in the intestinal type, and was not found in diffuse types of disease.ConclusionsThis study found that genetic polymorphisms of GSTP1 were associated with H. pylori-associated gastric cancer only during the advanced stage of gastric cancer, with intestinal-type histology evident in H. pylori-positive subjects.
| S-EPMC2871579 | biostudies-literature