Glutathione S-transferase P1 Ile105Val Polymorphism Research Articles

Multiple logistic regression analysis predicts cancer risk among tobacco usage with glutathione S-transferase p1 genotyping in patients with head and neck cancer.

Numerous studies have been investigated to understand the association between glutathione S-transferase P1 (GSTP1) polymorphism and risk of head and neck cancer (HNC) but yielded contradictory results, and no studies could confirm polymorphism in GSTP1 and that tobacco usage increases the risk of HNCs. Therefore, this study aimed to understand the association of GSTP1 Ile105Val polymorphism with or without tobacco usage in carcinogenesis and clinicopathological characteristics of patients with HNC. Binary logistic regression analysis was performed to predict HNC risk with tobacco use and GSTP1 genotyping. Five predictor variables such as gender, age, tobacco usage, familial, and GSTP1 genotypes were included in the model. The results of the logistic regression analysis show that the full model which considered all the five independent variables together was statistically significant, log-likelihood = -111.820, and all slopes are zero: G = 74.297, degree of freedom (DF) = 5, P = 0.000. The strongest predictor in this model is tobacco usage (odds ratio = Z = -5.16, P = 0.000). The study concludes that multiple logistic regression analysis model could predict the risk factors in case-control studies where control samples are compromised.

Glutathione S-transferase P1 Ile105Val Polymorphism and Male Infertility Risk: An Updated Meta-analysis.

Background:Several 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.Methods:The PubMed, EMBASE, China National Knowledge Infrastructure (CNKI), and Wanfang databases were searched. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to estimate the strength of the association.Results:A 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.Conclusions:The GSTP1 Ile105Val polymorphism might not be associated with male infertility risk, and thus additional well-designed studies with larger sample size are warranted.

Associations of the glutathione S-transferase P1 Ile105Val genetic polymorphism with gynecological cancer susceptibility: a meta-analysis.

The association between the glutathione S-transferase P1 (GSTP1) Ile105Val polymorphism and gynecological cancer susceptibility has been evaluated in many studies. However, the results remain controversial. Thus, this meta-analysis, based on 10 published case-control studies, was designed to clarify the association of the GSTP1 Ile105Val polymorphism with gynecological cancer risk. Our results suggested that there was no significant association between the GSTP1 Ile105Val polymorphism and the risk of gynecological cancer in all genetic models (GG vs. AA: odds ratio [OR] = 1.41, 95% confidence interval [CI] = 0.75-2.26; AG vs. AA: OR = 1.13, 95% CI = 0.74-1.73; AG/GG vs. AA: OR = 1.17, 95% CI = 0.75-1.81; GG vs. AA/AG: OR = 1.38, 95% CI = 0.79-2.42). Similarly, in the subgroup analyses by cancer type, ethnicity, and smoking status, no significant association with any genetic model was observed. In conclusion, the results of our meta-analysis suggest that the GSTP1 Ile105Val polymorphism is not associated with the development of gynecological cancer.

The Relationship Between Glutathione S-Transferase-P1 and Beta-2 Adrenoreceptor Genotypes with Asthmatic Patients in the Turkish Population.

Individual differences in the activity of enzymes that metabolize xenobiotics can impact health and disease. Beta-2 adrenoreceptor (ADRB2) is a functional G-coupled protein expressed in the vascular endothelium of lungs, alveolar walls, and the ganglions of cholinergic nerves which induces bronchodilation in response to catecholamines. Glutathione S-Transferase-P1 (GSTP1) is a candidate pi class GST gene, which controls pi class glutathione S-transferase activity. In this study we determined the relationship between the ADRB2 Arg16Gly polymorphism and GSTP1 polymorphisms, involved in bronchodilator response and oxidative stress, respectively, with susceptibility to asthma. In this study, 129 asthmatic patients and 127 healthy control cases were recruited to determine ADRB2 and GSTP1 genotypes by allele-specific polymerase chain reaction and restriction fragment length polymorphism assays, respectively. The ADRB2 genotype frequencies of the patients and control cases were found to be 10.9% (Arg16Arg), 48.8% (Arg16Gly), and 40.3% (Gly16Gly) and 24.4% (Arg16Arg), 36.2% (Arg16Gly), and 39.4% (Gly16Gly), respectively. GSTP1 genotype frequencies of patients and control cases were found to be 55% (Ile105Ile), 43.4% (Ile105Val), and 1.6% (Val105Val) and 75.6% (Ile105Ile), 22% (Ile105Val), and 2.4% (Val105Val), respectively. In the case of the GSTP1 gene, we found statistically significant differences in the genotype frequency of Ile105Val and the allele frequency of Val105 in the asthmatic group compared with the controls. Moreover, we observed a relationship between allele frequencies and clinical phenotypes including atopia nocturnal dyspnea, and steroid dependency in the asthmatic patients. Our results suggest that the GSTP1 Ile105Val polymorphism may be linked to the severeness of airway dysfunction.

GSTP1 Ile105Val and XRCC1 Arg399Gln gene polymorphisms contribute to the clinical outcome of patients with advanced non-small cell lung cancer.

Glutathione S-transferase P1 (GSTP1) and X-ray repair cross-complementing group 1 (XRCC1) genetic variations may in-fluence the efficacy of chemotherapy in various cancers. We investi-gated the possible roles of GSTP1 Ile105Val and XRCC1 Arg194Trp, and Arg399Gln gene polymorphisms in the prognosis of advanced non-small cell lung carcinoma (NSCLC) patients with cisplatin-based chemotherapy. Between January 2010 and December 2012, this study consecutively recruited 141 patients with advanced NSCLC from the First People's Hospital of Yunnan Province. Logistic regression analy-sis showed that individuals carrying the GG genotype were associated with a better response to chemotherapy than those with the wide-type genotype, with an adjusted odds ratio (95% confidence interval, CI) of 4.07 (1.06-25.06). Moreover, we observed that the AA genotype of XRCC1 Arg399Gln was correlated with a greater complete response + partial response to chemotherapy than that with the GG genotype (odds ratio = 2.71, 95%CI = 1.13-10.08). Based on the Cox hazard proportional model, the GG genotype of GSTP1 Ile105Val was found to be associated with a lower risk of death from all causes as compared to that with the AA genotype (hazard ratio = 0.07, 95%CI = 0.01-0.34). In summary, we suggest that GSTP1 Ile105Val and XRCC1 Arg399Gln polymorphisms could influence the response to chemotherapy and sur-vival of advanced NSCLC.

EVALUATION OF GLUTATHIONE-S-TRANSFERASE P1 POLYMORPHISM AND ITS RELATION TO BONE MINERAL DENSITY IN EGYPTIAN CHILDREN AND ADOLESCENTS WITH BETA- THALASSEMIA MAJOR

BackgroundOsteoporosis is a major complication of beta thalassemia major (TM). Increased oxidative stress and its controlling genes were linked to osteoporosis. Ile105 Val variant is a functional polymorphism of Glutathione S-transferase P1 (GSTP1), with reduced anti-oxidative property. No data are available about this variant or its association with osteoporosis among thalassemia patients yet.ObjectivesTo investigate Ile105Val polymorphism and its possible association with bone mineral density (BMD) values in a group of TM children.MethodsThirty five TM children and 30 age and sex matched healthy controls were included. Liver and renal functions, serum ferritin, calcium, phosphorous, alkaline phosphatase and osteocalcin were assayed. BMD was determined by DXA with calculation of Z-scores at lumbar spine (LS) and femoral neck (FN). Height for age Z- score (HAZ) adjusted BMD Z-scores were calculated. GSTP1 Ile105Val polymorphism was studied by polymerase chain reaction-restriction fragment length polymorphism.ResultsThe relative frequency of 105 Val allele was significantly higher in TM patients than the controls (p<0.0001). Significant association between genotype subgroups and BMD parameters was detected. Compared to wild homozygotes, polymorphic homozygotes had lower LS-BMD (p =0.029), LS-BMD Z –score (p=0.008 ), LS- BMD haz - Z-score (p=0.011), FN- BMD (p= 0.001), FN- BMD Z –score (p=0.02) and FN-BMD haz - Z-score (p=0.001). They exhibited higher osteocalcin levels compared to heterozygotes and wild homozygotes (p=0.012, p=0.013, respectively).ConclusionIle105Val polymorphism was frequent among TM patients and could increase their susceptibility to reduced BMD. Large sample studies are required to confirm these findings.

Association of glutathione S-transferase pi (GSTP1) Ile105Val polymorphism with the risk of skin cancer: a meta-analysis.

Numerous epidemiological studies have evaluated the association of Glutathione S-transferase P1 (GSTP1) Ile105Val polymorphism with the risk of skin cancer. However, the results remain inconclusive. To derive a more precise estimation of the association between the GSTP1 Ile105Val polymorphism and skin cancer risk, a meta-analysis was performed. A comprehensive search was conducted to identify the eligible studies. We used odds ratios (ORs) with 95 % confidence intervals (CIs) to assess the association of GSTP1 Ile105Val polymorphism with skin cancer risk. Thirteen case-control studies in nine articles, which included a total of 1504 cases and 2243 controls. Overall, we found that GSTP1 Ile105Val polymorphism was not associated with skin cancer risk. Furthermore, subgroup analysis by histological types showed that GSTP1 Ile105Val polymorphism was associated with risks of malignant melanoma under the dominant model (Val/Val + Val/Ile vs. Ile/Ile: OR 1.230, 95 % CI 1.017-1.488, P = 0.033). However, lack of association between GSTP1 Ile105Val polymorphism and BCC and SCC risk in all genetic models. Our meta-analysis suggested that the GSTP1 Ile105Val polymorphism might be associated with increased risk of malignant melanoma in Caucasian population.

Association of GSTP1 and RRM1 Polymorphisms with the Response and Toxicity of Gemcitabine-cisplatin Combination Chemotherapy in Chinese Patients with Non-small Cell Lung Cancer

Previous studies showed that genetic polymorphisms of glutathione S-transferase P1 (GSTP1) were involved in glutathione metabolism and genetic polymorphisms of ribonucleotide reductase (RRM1) were correlated with DNA synthesis. Here we explored the effects of these polymorphisms on the chemosensitivity and clinical outcome in Chinese non-small cell lung cancer (NSCLC) patients treated with gemcitabine-cisplatin regimens. DNA sequencing was used to evaluate genetic polymorphisms of GSTP1 Ile105Val and RRM1 C37A-T524C in 47 NSCLC patients treated with gemcitabine-cisplatin regimens. Clinical response was evaluated according to RECIST criteria after 2 cycles of chemotherapy and toxicity was assessed by 1979 WHO criteria (acute and subacute toxicity graduation criteria in chemotherapeutic agents). There was no statistical significance between sensitive and non-sensitive groups regarding the genotype frequency distribution of GSTP1 Ile105Val polymorphism (p>0.05). But for RRM1 C37A-T524C genotype, sensitive group had higher proportion of high effective genotype than non-sensitive group (p=0.009). And according to the joint detection of GSTP1 Ile105Val and RRM1 C37A-T524C polymorphisms, the proportion of type A (A/A+high effective genotype) was significantly higher in sensitive group than in non-sensitive group (p=0.009). Toxicity showed no correlation with the genotypes between two groups (p>0.05). Compared with single detection of genetic polymorphisms of GSTP1 Ile105Val or RRM1 C37A-T524C, joint detection of both may be more helpful for patients with NSCLC to receive gemcitabine-cisplatin regimens as the first-line chemotherapy. Especially, genetic polymorphism of RRM1 is more likely to be used as an important biomarker to predict the response and toxicity of gemcitabine-cisplatin combination chemotherapy in NSCLC.

Glutathione S-transferase P1, gene-gene interaction, and lung cancer susceptibility in the Chinese population: An updated meta-analysis and review.

To assess the impact of glutathione S-transferase P1 (GSTP1) Ile105Val polymorphism on the risk of lung cancer in the Chinese population, an updated meta-analysis and review was performed. Relevant studies were identified from PubMed, Springer Link, Ovid, Chinese Wanfang Data Knowledge Service Platform, Chinese National Knowledge Infrastructure, and Chinese Biology Medicine published through January 22, 2015. The odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to estimate the strength of the associations. A total of 13 case-control studies, including 2026 lung cancer cases and 2451 controls, were included in this meta-analysis. Overall, significantly increased lung cancer risk was associated with the variant genotypes of GSTP1 polymorphism in the Chinese population (GG vs. AA: OR=1.36, 95% CI=1.01-1.84). In subgroup analyses stratified by geographic area and source of controls, the significant results were found in population-based studies (GG vs. AA: OR=1.62, 95% CI: 1.13-2.31; GG vs. AG: OR=1.49, 95% CI: 1.03-2.16; GG vs. AA+AG: OR=1.55, 95% CI: 1.12-2.26). A gene-gene interaction analysis showed that there was an interaction for individuals with combination of GSTM1 (or GSTT1) null genotype and GSTP1 (AG+GG) mutant genotype for lung cancer risk in Chinese. This meta-analysis suggests that GSTP1 Ile105Val polymorphism may increase the risk of lung cancer in the Chinese population.

A systemic review of glutathione S-transferase P1 Ile105Val polymorphism and colorectal cancer risk.

To investigate the correlation between glutathione S-transferase P1 (GSTP1) Ile105Val polymorphism and colorectal cancer (CRC) risk. Studies 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. A 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. GSTP1 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.

Association between susceptibility to advanced pelvic organ prolapse and glutathione S-transferase P1 Ile105Val polymorphism

ObjectiveOxidative stress is associated with the pathogenesis of pelvic organ prolapse (POP). Because glutathione S-transferases (GSTs) are the major detoxification enzymes which protect cells against oxidative stress, genetic variations in the GST gene may modulate the risk of POP. This study aimed to determine the association between advanced POP and the polymorphisms of GSTM1, GSTT1 and GSTP1 (rs1695). Study designThis is a hospital-based case-control study. The POP group consisted of 189 women diagnosed with POP stage III or IV, and the control group consisted of 156 postmenopausal women with POP stage 0 or I. The GSTM1 and GSTT1 null mutations were detected by multiplex PCR, and the GSTP1 Ile105Val polymorphism was genotyped by real-time PCR analysis using a TaqMan assay. ResultsThere was no significant association between the GSTM1 and GSTT1 null mutations and advanced POP (p>0.05). The distribution of the GSTP1 Ile105Val genotypes, however, was significantly different between the POP and control groups (AA/AG/GG rates=74.1%/25.9%/0% vs. 64.1%/32.1%/3.8%, p=0.008), and the G allele frequency was significantly lower in the POP group than in the control group (13.0% vs. 19.9%, p=0.014). Women with the non-AA genotype had a 0.63-fold lower risk of developing advanced POP than women with the AA genotype (95% CI, 0.39–0.99), and women with the G allele had a 0.60-fold lower risk of advanced POP than women with the A allele (95% CI, 0.40–0.90). ConclusionsThe GSTP1 Ile105Val polymorphism is a protective factor against advanced POP.

Association between GSTP1 Ile105Val polymorphism and glioma risk: A systematic review and meta-analysis

Glutathione S-transferase P1 (GSTP1) gene Ile105Val polymorphism has been suggested to be involved in the development of glioma. However, the results from the studies regarding the association between GSTP1 Ile105Val polymorphism and glioma risk have been inconsistent. Thus, we performed a meta-analysis to investigate this association. Pooled odds ratios (ORs) with 95% confidence intervals (95%CIs) were calculated using random or fixed effects model. Nine studies with 2,078 cases and 3,970 controls were finally included into this meta-analysis. The results suggested there was no association between GSTP1 Ile105Val polymorphism and glioma risk under recessive model (OR = 1.138, 95%CI = 0.966-1.341, Pheterogeneity = 0.088, P = 0.123). Subgroup analyses by ethnicity showed there was also no association between GSTP1 Ile105Val polymorphism and glioma risk in mixed populations under recessive model (OR = 1.199, 95%CI = 0.928-1.549, Pheterogeneity = 0.060, P = 0.166) and Caucasian populations (OR = 1.097, 95%CI = 0.885-1.360, Pheterogeneity = 0.186, P = 0.398). In conclusion, the meta-analysis suggests that there is no association between GSTP1 Ile105Val polymorphism and glioma risk. However, more well-designed and larger studies are needed to further assess this association.

GSTP1 Ile105Val Polymorphism and Prostate Cancer Risk: Evidence from a Meta-Analysis

BackgroundGlutathione S-transferase P1 (GSTP1) is thought to be involved in the detoxification of reactive carcinogen metabolites. Numerous epidemiological studies have evaluated the association of GSTP1 Ile105Val polymorphism with the risk of prostate cancer. However, the results remain inconclusive. To derive a more precise estimation, a meta-analysis was performed.Methodology/Principal FindingsA comprehensive search was conducted to identify the eligible studies. We used odds ratios (ORs) with 95% confidence intervals (CIs) to assess the strength of the relationship. The overall association was not significant (Val/Val vs. Ile/Ile OR = 1.06, 95% CI = 0.90–1.25, P = 0.50; Val/Val vs. Val/Ile+Ile/Ile: OR = 1.07, 95% CI = 0.91–1.25, P = 0.44). In subgroup analyses by ethnicity and prostate cancer grade, the similar results were observed. However, in stratified analysis by clinical stage, we found a significant association with low-stage prostate cancer (Val/Val vs. Ile/Ile: OR = 2.70, 95% CI = 1.73–4.22, P<0.001; Val/Val vs. Val/Ile+Ile/Ile: OR = 2.14, 95% CI = 1.38–3.33, P = 0.001). Moreover, there was no statistically significant evidence of multiplicative interactions neither between the GSTP1 Ile105Val polymorphism and GSTM1, nor between smoking status and GSTP1 on prostate cancer risk.ConclusionsThis meta-analysis showed that GSTP1 Ile105Val polymorphism might not be significantly associated with overall prostate cancer risk. Further stratified analyses showed a significant association with low-stage prostate cancer.

GSTP1 Ile105Val polymorphism and colorectal cancer risk: An updated analysis

BackgroundMany studies have investigated the association between the Glutathione S transferase-P1 (GSTP1) Ile105Val polymorphism and colorectal cancer (CRC) susceptibility, but the results were conflicting. The aim of this study is to quantitatively summarize the relationship between this polymorphism and CRC risk. MethodsTwo investigators independently searched the Medline, Embase, China National Knowledge Infrastructure (CNKI) and Chinese Biomedicine databases for studies published before December 2012. Summary odds ratios (ORs) and 95% confidence intervals (95% CIs) for GSTP1 polymorphism and CRC were calculated in a fixed-effects model (the Mantel–Haenszel method) and a random-effects model (the DerSimonian and Laird method) when appropriate. ResultsThis meta-analysis included 29 case–control studies, which included 8160 CRC cases and 10,450 controls. Overall, the variant genotypes (ValVal and IleVal) of the Ile105Val were not associated with CRC risk when compared with the wild-type IleIle homozygote. Similarly, no associations were found in the dominant and recessive models. When stratifying for ethnicity, source of controls, study sample size and genotyping methods, no evidence of significant association was observed in any subgroup, except among those studies taking others as genotyping methods (recessive model, OR=0.71, 95%CI=0.52–0.96). Limiting the analysis to the studies within Hardy–Weinberg equilibrium, the results were persistent and robust. No publication bias was found in the present study. ConclusionThis updated meta-analysis suggests that the GSTP1 Ile105Val polymorphism may not be associated with CRC risk, while the observed decrease in risk of CRC may be due to small-study bias.

Quantitative assessment of the association between GSTP1 gene Ile105Val polymorphism and susceptibility to hepatocellular carcinoma

Glutathione S-transferase P1 (GSTP1) gene Ile105Val polymorphism has been suggested to be involved in the development of cancer. However, the results from the studies regarding the association between GSTP1 Ile105Val polymorphism and hepatocellular carcinoma risk have been inconsistent. Thus, we performed a meta-analysis to investigate the association. Published literature from PubMed, Chinese Biomedical Literature, and Wanfang databases was searched for eligible publications. Pooled odds ratios (ORs) with 95 % confidence intervals (95 %CIs) were calculated using random- or fixed-effects model. Six studies with a total of 1,843 participants were finally included into this meta-analysis. The results suggested there was no association between GSTP1 Ile105Val polymorphism and hepatocellular carcinoma risk under all genetic models (for ValVal vs. IleIle, OR = 0.79, 95 %CI 0.48-1.29, P = 0.341; for IleVal vs. IleIle, OR = 1.05, 95 %CI 0.84-1.30, P = 0.678; for the dominant model, OR = 0.91, 95 %CI 0.68-1.20, P = 0.498; and for the recessive model, OR = 0.76, 95 %CI 0.47-1.24, P = 0.269). Subgroup analyses by ethnicity showed there was also no association between GSTP1 Ile105Val polymorphism and hepatocellular carcinoma risk in Asians under all genetic models (All P values were more than 0.05), but GSTP1 Ile105Val polymorphism was associated with decreased risk of hepatocellular carcinoma in European under the recessive model (ValVal vs. IleVal/IleIle) (OR = 0.44, 95 %CI 0.20-0.98, P = 0.044). In conclusion, the meta-analysis suggests that there is little evidence for the association between GSTP1 Ile105Val polymorphism and hepatocellular carcinoma risk. However, more well-designed studies are needed to further assess this association.

Association between GSTP1 Ile105Val polymorphism and oxaliplatin-induced neuropathy: a systematic review and meta-analysis

The association between glutathione-S-transferase P1 (GSTP1) Ile105Val polymorphism and oxaliplatin-induced neuropathy has been investigated in a number of published studies. However, most of these studies were based on small sample sizes and the results remained inconsistent. To assess the relationship between GSTP1 gene Ile105Val polymorphism and its susceptibility to oxaliplatin-induced neuropathy, a meta-analysis of previous studies was conducted. Two investigators independently searched studies published up to December 2012 from the databases of PubMed, EMBASE and The Cochrane Library. The pooled effect was calculated as odds ratio (OR) and corresponding 95% confidence intervals (CIs) using fixed-effect or random-effect model. Twelve prospective trials and two retrospective clinical trials involving 2,191 participants met the inclusion criteria. Combined analyses of these studies showed no significant associations between GSTP1 Ile105Val polymorphism and oxaliplatin-induced neuropathy, yielding OR of 1.08 (95%CI 0.67-1.74, P=0.754) in dominant model. Similar results were also obtained in recessive model (OR=1.67, 95%CI 0.56-4.93, P=0.357) and allelic analysis (OR=1.22, 95%CI 0.67-2.24, P=0.513). Since significant heterogeneity across studies, the pooled effects were calculated by random-effect model. No evidence of publication biases was identified in this meta-analysis. This meta-analysis did not support the hypothesis that GSTP1 Ile105Val polymorphism was related to the occurrence of neurotoxicity in oxaliplatin-treated patients. Given the limited number of studies and potential bias, large-scale and well-designed clinical trials should be needed to confirm these hypotheses.

Glutathione S‐transferase P1 Ile105Val polymorphism modulates allergen‐induced airway inflammation in human atopic asthmatics in vivo

Glutathione S-transferase P1 is a Phase II cytoprotective and detoxifying enzyme that is widely expressed in human airways. The glutathione S-transferase P1 Ile105Val polymorphism has been linked with atopic disorders and asthma. Yet, little remains known about the regulation of allergic inflammation by glutathione S-transferase P1 in human asthmatics. To establish the effect of the glutathione S-transferase P1 Ile105Val polymorphism on allergen-induced airway inflammation and oxidant stress, and non-specific bronchial hyperresponsiveness to methacholine and reactivity to specific allergen in mild human atopic asthmatics in vivo. Five Val(105)/Val(105) , twelve Val(105)/Ile(105) and twenty Ile(105)/Ile(105) mild atopic asthmatics underwent methacholine challenge, inhaled allergen challenge and endobronchial allergen provocation through a bronchoscope. A panel of inflammatory cytokines and chemokines, F2 -isoprostanes and isofuranes, markers of oxidative stress, thromboxane B2 and immunoglobulin E were measured in bronchoalveolar lavage fluid at baseline and 24 h after allergen instillation. Asthmatics with glutathione S-transferase P1 Val(105)/Val(105) compared with asthmatics with the glutathione S-transferase P1 Val(105)/Ile(105) and Ile(105)/Ile(105) had greater generation of acute phase cytokines (TNF-α, IL-6, CXCL8), IL-12, CCL11, thromboxane B2 and immunoglobulin E at 24 h after local allergen challenge. The GSTP1 genotype had no effect on airway hyperresponsiveness to methacholine and the reactivity to specific allergen. The glutathione S-transferase P1 Ile105Val polymorphism markedly modifies allergen-provoked airway inflammation in atopic asthmatics in vivo. Modulation of the biochemical milieu in response to allergen provides a mechanistic explanation for regulatory effects of glutathione S-transferase P1 polymorphism on airway pathophysiology, and may guide improvement of future therapeutic methods in human atopic asthmatics. These findings must me confirmed in a larger study population of asthmatics with various ethnicities.

Association between the GSTP1 Ile105Val polymorphism and prostate cancer risk: a systematic review and meta-analysis

Many studies have reported the role of glutathione S-transferase P1 (GSTP1) Ile105Val polymorphism with prostate cancer (PCa) risk. However, these studies have yielded conflicting results. Hence, we performed this meta-analysis to investigate the association between GSTP1 Ile105Val polymorphism and PCa in different inheritance models. A total of 13 eligible studies were pooled into this meta-analysis. There was significant association between the GSTP1 Ile158Val variant genotypes and PCa for Ile/Ile vs Val/Val comparison [odds ratio (OR) =0.705; I (2) =63.7 %; 95 % confidence interval (95 % CI) = 0.508-0.977], Ile/Val vs Val/Val comparison (OR=0.736; I (2) =8.0 %; 95 % CI=0.613-0.883), and dominant model (OR=0.712; I (2) =45.5 %; 95 % CI=0.555-0.913). However, no associations were detected for other genetic models. In the stratified analysis by ethnicity, significant associations between GSTP1 Ile105Val polymorphism and PCa risk were also found among Caucasians (Ile/Ile vs Val/Val comparison OR=0.818, I (2) =0.0 %, 95 % CI=0.681-0.982; Ile/Val vs Val/Val comparison OR=0.779, I (2) =0.0 %, 95 % CI=0.651-0.933; and dominant model OR=0.794, I (2) =0.0 %, 95 % CI=0.670-0.941), while there were no associations found for other genetic models. However, no associations were found in Asians and African-Americans for all genetic models when stratified by ethnicity. In conclusion, our meta-analysis indicates that GSTP1 Ile105Val polymorphisms contributed to the PCa susceptibility. However, a study with the larger sample size is needed to further evaluate gene-environment interaction on GSTP1 Ile105Val polymorphisms and PCa risk.

Quantitative assessment of the association between glutathione S-transferase P1 Ile105Val polymorphism and bladder cancer risk

Previous studies investigating the association between glutathione S-transferase P1 (GSTP1) Ile105Val polymorphism and bladder cancer risk reported controversial results. This study aimed to quantify the strength of the association between GSTP1 Ile105Val polymorphism and bladder cancer risk by performing a meta-analysis. We searched the PubMed, Embase, and Wanfang databases for publications on the association between GSTP1 Ile105Val polymorphism and bladder cancer risk. We estimated the pooled odds ratios (ORs) with their confidence intervals (95 %CIs) to assess the association. Twenty-five individual studies with a total of 12,360 subjects were finally included. Meta-analysis of all 25 studies showed that GSTP1 Ile105Val polymorphism was associated with increased risk of bladder cancer risk under four genetic comparison models (for G versus A, random-effect OR=1.19, 95 %CI 1.05-1.35; for GG versus AA, random-effect OR=1.49, 95 %CI 1.12-1.97; for GG/GA versus AA, random-effect OR=1.20, 95 %CI 1.03-1.39; for GG versus GA/AA, random-effect OR=1.41, 95 %CI 1.10-1.80). Sensitivity analysis showed that GSTP1 Ile105Val polymorphism was still associated with bladder cancer risk under three genetic comparison models (for G versus A, random-effects OR=1.13, 95 %CI 1.01-1.26; for GG versus AA, random-effects OR=1.29, 95 %CI 1.01-1.65; for GG versus GA/AA, random-effects OR=1.19, 95 %CI 1.04-1.35). No evidence of publication bias was observed. This meta-analysis shows that there is an obvious association between GSTP1 Ile105ValIle105Val polymorphism and bladder cancer risk, and GSTP1 ILE105VAL polymorphism contributes to bladder cancer risk.

Glutathione S-transferase P1 Ile105Val polymorphism contributes to increased risk of gastric cancer in East Asians

Glutathione S-transferase P1 (GSTP1) is an important enzyme playing critical roles in the phase II detoxification pathway. There were many studies investigating the association between GSTP1 gene Ile105Val polymorphism and gastric cancer risk, but studies from East Asians reported inconsistent findings. We performed a meta-analysis to investigate the association in East Asians. Published literature from PubMed and Chinese Biomedical Literature databases were searched for eligible publications. Pooled odds ratios (ORs) with 95 % confidence intervals (95 %CIs) were calculated using random or fixed-effect model according the between-study heterogeneity. A total of 12 studies with 2,552 cases and 5,474 controls were finally included into the meta-analysis. Meta-analysis of those 12 studies showed that there was an obvious association between GSTP1 Ile105Val polymorphism and gastric cancer risk in East Asians under three genetic models (for valine vs. isoleucine, OR=1.32, 95 %CI 1.05-1.66, P=0.015; for ValVal vs. IleIle, OR=2.00, 95 %CI 1.34-2.98, P=0.001; for the recessive model, OR=1.96, 95 %CI 1.35-2.83, P<0.001). Sensitivity analysis by removing one study at a time suggested the pooled results were stable under the three genetic models above. There was no risk of publication bias. In conclusion, the meta-analysis suggests that there is a strong evidence for the association between GSTP1 Ile105Val polymorphism and increased risk of gastric cancer in East Asians and contributes to increased risk of gastric cancer in East Asians.