Association between GSTP1, GSTM1 and GSTT1 polymorphisms involved in xenobiotic metabolism and head and neck cancer development

Polymorphisms in the glutathione S-transferase superfamily genes that encodes enzymes involved in the phase II xenobiotic metabolism may lead head and neck cancer development. In this study we investigate the association of A313G and C341T GSTP1 polymorphisms, GSTM1 and GSTT1 null genotypes in the head and neck cancer development, interactions between these polymorphisms,the tumor histopathologic parameters and risk factors (smoking and drinking) were also evaluated in the case–control study. 775 individuals (261 patients/514 controls) were included in the study. Molecular analyzes were performed by PCR and PCR–RFLP; and statistical analyzes by Chi square and multiple logistic regression. Chi square test showed that only the genotype frequencies for GSTM1 and GSTT1 were in Hardy–Weinberg disequilibrium in both groups. Significant results with p ≤ 0.05 showed that age ≥ 48 years (OR = 11.87; 7.55–18.65), smoking (OR = 4.25; 2.70–6.69), drinking (OR = 1.59; 1.02–2.46) were possible predictors for the head and neck cancer development and the presence of A313G GSTP1 polymorphism (OR = 0.62; 0.42–0.92) decreased the risk for this disease. Individuals with the 313AG/GG GSTP1 and age ≥ 48 years (OR = 0.59; 0.38–0.91), male gender (OR = 0.54; 0.35–0.83), smokers (OR = 0.63; 0.40–0.99) and drinkers (OR = 0.57; 0.35–0.95); the GSTM1 null genotype and age < 48 years (OR = 2.46; 1.09–5.55); the GSTT1 null genotype and primary anatomical sites of pharynx (OR = 0.37; 0.17–0.79) and larynx (OR = 3.60; 1.93–6.72), can modulate the risk for the disease development. The variables age ≥ 48 years, smoking and drinking can be predictors for head and neck cancer development; moreover, A313G GSTP1 polymorphism, GSTM1 and GSTT1 null genotypes can modulate the risk for this disease.     

Glutathione S-transferase M1, T1, and P1 polymorphisms and risk of glioma: a meta-analysis

The relationship between genetic polymorphisms of glutathione S-transferase (GST) and the development of glioma has been investigated in several epidemiologic studies. However these studies report inconsistent results. In order to quantitatively summarise the evidence for such a relationship, a meta-analysis is conducted. The PubMed database was searched from inception to January 2012 to identify relevant studies that met pre-stated inclusion criteria. We also reviewed reference lists from retrieved articles. Two researchers evaluated study eligibility and extracted the data independently, and disagreements were resolved by discussion. The principal outcome measure was the odds ratio (OR) with 95 % confidence interval (CI) for the risk of glioma associated with GSTM1, GSTT1, GSTP1 I105V or GSTP1 A114V. This meta-analysis included 11 case–control studies, which included 2,404 glioma cases and 6,379 controls. The combined results based on all studies showed that there was no association between any of the GST variants and the risk of glioma (for GSTM1: pooled OR = 1.03; 95 % CI, 0.92–1.15; for GSTT1: pooled OR = 1.12; 95 % CI, 0.90–1.40; for GSTP1 I105V: pooled OR = 0.92; 95 % CI, 0.64–1.31 and for GSTP1 A114V: pooled OR = 1.14; 95 % CI, 0.97–1.34). Subgroup analyses showed that GSTP1 A114V genotype was associated with an increased risk of other histopathologic glioma except glioblastoma multiforme (GBM) (pooled OR = 1.30; 95 % CI = 1.06–1.60); no relationship was found between other GST variants and histopathologic groups. In conclusion, our meta-analysis suggests no association between GST variants and the risk of glioma. However, the significant risk elevation is present between GSTP1 A114V genotype and other histopathologic glioma except GBM.     

Glutathione S-transferase polymorphisms and survival in African-American and White colorectal cancer patients

Background: Glutathione S-transferase (GST) enzymes are involved in electrophile detoxification. The authors investigated the association between GST genotype and survival in a racially diverse, population-based cohort of colorectal cancer (CRC) patients followed for a median of 9.6 years. Methods: Interviews were conducted with 315 African-American and White CRC patients in Connecticut, 1987–1991. Tumor tissue (n = 197) was later retrieved from hospital of diagnosis and assayed using multiplex PCR (GSTM1 and GSTT1) and PCR and RFLP analysis (GSTP1). Cox proportional hazards models provided adjusted hazard ratios (HR) and 95% confidence intervals (CI). Results: Individuals with Ile/Val or Val/Val GSTP1 genotypes had a decreased risk of death (multivariate adjusted HR = 0.72, 95% CI: 0.48, 1.09) relative to those with wild type (Ile/Ile). Among those who received chemotherapy, this benefit was more pronounced (HR = 0.35, 95% CI: 0.16, 0.79); the interaction of reduced function GSTP1 genotype and chemotherapy was significant (P = 0.05). GSTM1 and GSTT1 genotype were not associated with survival. GSTM1, GSTT1, and GSTP1 genotype did not vary by race and did not contribute significantly to the survival disadvantage observed in African-Americans. Conclusions: In summary, GSTP1 genotype may play a role in CRC survival in African-Americans and Whites, particularly among those who receive chemotherapy.     

The Association Between Polymorphic Genotypes of Glutathione S-Transferases and COPD in the Turkish Population

Although smoking is regarded as the most important causal factor in chronic obstructive pulmonary disease (COPD), only 10–20% of smokers develop symptomatic COPD, which indicates the presence of genetic predisposing factors in its pathogenesis. This study investigates the association between gene polymorphysims of glutathione S-transferases (GSTs) and COPD. Blood samples were taken from 149 patients and 150 healthy controls. Polymorphisms of GSTT1, GSTM1, and GSTP1 were genotyped using Real-Time PCR. Multivariate logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals between specific genotypes and COPD. There was no difference in the frequencies of the genotypes of GSTM1 and GSTT1 between the groups, but the GSTP1 Ile/Ile genotype was significantly higher in the patients than in the controls (61.1% vs. 38%). GSTP1 Ile/Val and Val/Val genotypes were associated with a decreased risk of COPD when compared to the Ile/Ile genotype (2.12-fold and 4-fold, respectively). Thus we suggest that the Val allele of GSTP1 may have a protective effect for development of COPD. Furthermore, when we evaluated the association between GSTP1 genes and smoking status, smokers with the GSTP1 Ile allele had an increased risk for the development of COPD. Among the combinations of the genotypes, the combination of GSTM1, GSTT1 null, and GSTP1 Val/Val was associated with the maximal increased risk (12-fold) of COPD. Thus to explain the ethiopathogenesis of COPD, investigation of a single gene family is inadequate. Based on our results and the previous data, further studies should be focused on the GSTP1 gene and the interactions with other genes such as polymorphisms of N-acetyltransferases, GSTM1 and GSTT1, microsomal epoxide hydrolase, and allelic variants of cytochrome P450.     

Glutathione S-transferase polymorphisms, asthma susceptibility and confounding variables: a meta-analysis

Oxidative stress is one of the main risk factors for asthma development. Glutathione S-transferases play an important role in antioxidant defences and may influence asthma susceptibility. In particular, GSTM1 and GSTT1 positive/null genotypes and the GSTP1*Ile105 Val polymorphism have been analyzed in a number of genetic association studies, with conflicting outcomes. Two previous meta-analyses have attempted to clarify the associations between GST genes and asthma, but these studies have also showed contrasting results. Our aim was to perform a meta-analysis that included independent genetic association studies on GSTM1, GSTP1, and GSTT1, evaluating also the effect of potential confounding variables (i.e. ethnicity, population age, and urbanization). Systematic review and meta-analysis of the effects of GST genes on asthma were conducted. The meta-analyses were performed using a fixed or, where appropriate, random effects model. The meta-analysis of the GSTM1 (n = 35), GSTT1 (n = 31) and GSTP1 (n = 28) studies suggests that no significant associations with asthma susceptibility were observed for GSTM1 and GSTP1 gene polymorphisms, whereas a significant outcome was detected for the GSTT1 positive/null genotype (pooled OR = 1.33, 95 %CI = 1.10–1.60). However, high between-study heterogeneity was identified in all the general analyses (p _{heterogenetity} < 0.05). The stratification analysis seems to explain the heterogeneity only in few cases. This picture is probably due to the interactive process of genetics and environment that characterizes disease pathogenesis. Further studies on interactions of GST genes with the potential oxidative stress sources and with other antioxidant genes are needed to explain the role of GST enzymes in asthma.     

The role of GSTM1, GSTT1, GSTP1, and OGG1 polymorphisms in type 2 diabetes mellitus risk: a case-control study in a Turkish population

The aim of the present study was to investigate the role of some polymorphisms in GSTs (GSTM1, GSTT1 and GSTP1) which are very important protective mechanisms against oxidative stress and in OGG1 gene which is important in DNA repair, against the risk of type 2 diabetes mellitus (T2DM). 127 T2DM and 127 control subjects were included in the study. DNA was extracted from whole blood. Analyses of GSTM1 and GSTT1 gene polymorphisms were performed by allele specific PCR and those of GSTP1 Ile105Val and OGG1 Ser326Cys by PCR-RFLP. Our data showed that GSTM1 null genotype frequency had a 2-6 times statistically significant increase in a patient group (OR=3.841, 95% CI=2.280-6.469, p<0.001) but no significance with GSTT1 null/positive and GSTP1 Ile105Val genotypes was observed. When T2DM patients with OGG1 Ser326Cys polymorphism were compared with patients with a wild genotype, a 2-3 times statistically significant increase has been observed (OR 1.858, 95% CI=1.099-3.141, p=0.021). The combined effect of GSTM1 null and OGG1 variant genotype frequencies has shown to be statistically significant. Similarly, the risk of T2DM was statistically increased with GSTM1 null (OR=3.841, 95% CI=2.28-6.469), GSTT1 null+GSTP1 (H+M) (OR=4.118, 95% CI=1.327-12.778) and GSTM1 null+OGG1 (H+M) (OR=3.322, 95% CI=1.898-5.816) and GSTT1 null+OGG1 (H+M) (OR=2.179, 95% CI=1.083-4.386) as compared to the control group. According to our study results, it has been observed that the combined evaluation of GSTM1-GSTT1-GSTP1 and OGG1 Ser326Cys gene polymorphisms can be used as candidate genes in the etiology of T2DM, especially in the development of T2DM.     

Impact of glutathione-S-transferase gene polymorphisms on enzyme activity, lung function and bronchial asthma susceptibility in Egyptian children

Background

Asthma is a complex multifactorial disease with an obvious genetic predisposition. Polymorphisms of the glutathione-S-transferase (GST) genes are known risk factors for some environmentally-related diseases. The aim of the present study was to investigate the role of polymorphisms in the GSTT1, GSTM1 and GSTP1 genes and asthma susceptibility in Egyptian children, and to analyze their effect on GST activity and lung function.

Methods

GSTT1 and GSTM1 gene polymorphism was genotyped using the multiplex polymerase chain reaction (PCR) and GSTP1 ILe105Val polymorphism was determined using PCR-restriction fragment length polymorphism (PCR-RFLP) in 168 healthy and 126 asthmatic children (82 atopic and 44 nonatopic). Also GST enzyme activity and lung function were evaluated.

Results

Asthmatic children had a significant higher prevalence of the GSTM1 null (P = 0.003) and significant lower prevalence of GSTP1 Val/Val genotypes (P = 0.02) than control group. Lung function was significantly decreased in GSTM1 null genotype and GSTP1 Ile/Ile genotype. GSTP1 Val/Val genotypes and GSTM1 null genotype had a significant decrease in plasma GST activity.

Conclusions

GST genes polymorphisms may play an important role in pathogenesis and susceptibility to asthma in children.     

Glutathione S-Transferase M1, T1, P1 Genotypes and Risk for Development of Colorectal Cancer

The glutathione S-transferase (GST) supergene family is an important part of cellular enzyme defense against endogenous and exogenous chemicals, many of which have carcinogenic potential. The present investigation was conducted to detect a possible association between polymorphisms at the GSTM1, GSTT1, and GSTP1 genes and the interaction with cigarette smoking and colorectal cancer incidence. We examined 181 patients with colorectal cancer and 204 controls. DNA was extracted from whole blood, and the GSTM1, GSTT1, and GSTP1 polymorphisms were determined using a real-time polymerase chain reaction and fluorescence resonance energy transfer with a Light-Cycler instrument. Associations between specific genotypes and the development of colorectal cancer were examined by use of logistic regression analysis to calculate odds ratios (OR) and 95% confidence intervals (CI). The GSTM1 polymorphism was associated with an increased risk of developing colorectal cancer (OR = 1.62, 95% CI: 1.06–2.46). Also the risk of colorectal cancer associated with the GSTT1 null genotype was 1.64 (95% CI: 1.10–2.59). Statistically no differences were found between patients with colorectal cancer and control groups for the GSTP1 Ile/Ile, Ile/Val and Val/Val genotypes. In addition, the frequencies of the GSTM1 and GSTT1 deletion genotypes differed significantly between the cases and controls for current smokers; the GSTT1 null genotype especially is associated with a greater risk of colorectal cancer (OR = 2.44, 95% CI: 1.24–4.81). The GSTM1 and GSTT1 deletions were associated with an increased risk of developing a transverse or rectal tumor (OR = 1.86, 95% CI: 1.15–3.00; OR = 1.70, 95% CI: 1.02–2.84; respectively). The glutathione S-transferase polymorphisms were not associated with risk in patients stratified by age. The risk of colorectal cancer increased as putative high-risk genotypes increased for the combined genotypes of GSTM1 null, GSTT1 null, and either GSTP1 valine heterozygosity or GSTP1 valine homozygosity (OR = 2.69, 95% CI: 1.02–7.11). In conclusion, the results obtained in this study clearly suggest that those susceptibility factors related to different GST polymorphic enzymes are predisposing for colorectal cancer.     

Genetic polymorphism of lysyl oxidase,glutathione S-transferase M1, glutathione-S-transferase T1, and glutathione S-transferase P1 genes as risk factors for lung cancer in Egyptian patients

Lung cancer is a lethal malignancy and is affected by genetic polymorphisms that contribute to an individual’s susceptibility to developing the disease. Several studies on lung cancer showed conflicting results. The aim of this study is to investigate whether individual or combined modifying effects of LOX G/A, GSTM1 active/null, GSTT1 active/null and GSTP1 Ile/Val polymorphisms are related to the risk of lung cancer in relation to smoking in the Egyptian population. This study is a hospital-based case control study that included 200 patients and 200 control subjects. Genotyping of the 4 studied genes was determined by Multiplex PCR for GSTM1 and GSTT1 and Taq man SNP assay for GSTP1 and LOX genes. The LOX G/A and GSTP1 Ile/Val in both homozygous and heterozygous variants, and the GSTM1 and GSTT1 null genotype showed significant association with lung cancer. Combination between gene polymorphism and smoking increased the risk of developing cancer by 2.7 fold in the LOX GA+AA variant, 1.9 fold in the GSTM1 null variant, 4.8 fold in the GSTT1 null variant and 4.3 fold in the GSTP1 Ile/Val+Val/Val variant. The genetic combination (LOX GA+AA/GSTT1 active, LOX GG/GSTT1 null, LOX GA+AA/GSTT1 null, LOX GA+AA/GSTP1 Ile/Ile, LOX GG/GSTP1 Ile/Val+Val/Val and LOX GA+AA/GSTP1 Ile/Val+Val/Val) led to a higher lung cancer risk, compared to the reference group. The LOX GA/AA, GSTM1 null, GSTT1 null and GSTP1 Ile/Val, Val/Val genotypes contributed to increased lung cancer susceptibility. To the best of our knowledge, this is the first study of LOX genotyping in the Egyptian population. The combination of genotypes increased the risk of cancer, indicating the importance of gene–gene interaction and giving a targeted preventive approach.

     

Glutathione S-transferases gene polymorphisms and risk of male idiopathic infertility: a systematic review and meta-analysis

The Glutathione S-transferases (GSTs) polymorphisms have been implicated in susceptibility to male idiopathic infertility, but study results are still controversial. To investigate the genetic associations between GSTs polymorphisms and risk of male idiopathic infertility, a systematic review and meta-analysis were performed. Meta-analysis was performed by pooling odds ratio (OR) with its corresponding 95 % confidence interval (95 % CI) form studies in electronic databases up to March 16, 2012. Glutathione S-transferase M 1 (GSTM1) null genotype, Glutathione S-transferase T 1 (GSTT1) null genotype, and dual null genotype of GSTM1/GSTT1 were analyzed independently. 14 eligible studies with a total of 1,845 idiopathic infertility males and 1,729 controls were included. There were 13 studies on GSTM1 polymorphism, 10 ones on GSTT1 polymorphism and 5 ones on GSTM1-GSTT1 interaction analysis. Meta-analyses of total relevant studies showed GSTM1 null genotype was significantly associated with an increased risk of male idiopathic infertility (OR = 1.40, 95 % CI 1.07–1.84, P _OR = 0.015). The GSTM1-GSTT1 interaction analysis showed dual null genotype of GSTM1/GSTT1 was also significantly associated with increased risk of male idiopathic infertility (OR = 1.85, 95 % CI 1.07–3.21, P _OR = 0.028). Subgroup analyses by ethnicity showed the associations above were still statistically significant in Caucasians (For GSTM1, OR = 1.51, 95 % CI 1.11–2.05, P _OR = 0.009; For GSTM1/GSTT1, OR = 2.10, 95 % CI 1.51–2.91, P _OR < 0.001). This meta-analysis suggests GSTM1 null genotype contributes to increased risk of male idiopathic infertility in Caucasians, and males with dual null genotype of GSTM1/GSTT1 are particularly susceptible to developing idiopathic infertility.     

A meta-analysis of the association of glutathione S-transferase P1 gene polymorphism with the susceptibility of breast cancer

Glutathione S-transferase P1 (GSTP1) is one of the important mutant sites for the cancer risk at present. The conclusions of the published reports on the relationship between GSTP1 A/G gene polymorphism and the risk of breast cancer are still debated. This meta-analysis was performed to evaluate the association between GSTP1 and the risk of breast cancer. The association reports were identified from PubMed and Cochrane Library, and eligible studies were included and synthesized using meta-analysis method. 35 investigations were included into this meta-analysis for the association of GSTP1 A/G gene polymorphism and breast cancer susceptibility, consisting of 40,347 subjects (18,665 patients with breast cancer and 21,682 controls). The association between GSTP1 A/G gene polymorphism and breast cancer risk was not found for overall population, Caucasians and Africans. Interestingly, the GSTP1 A/G gene polymorphism was associated with the susceptibility of breast cancer in Asians (G allele: OR = 1.10, 95 % CI: 1.04–1.17, P = 0.001; GG genotype: OR = 1.36, 95 % CI: 1.14–1.62, P = 0.0008; AA genotype: OR = 0.92, 95 % CI: 0.85–0.98, P = 0.02). Furthermore, the GSTP1 A/G gene polymorphism was associated with the susceptibility of breast cancer for the analysis of the controls from hospital. In conclusion, GSTP1 A/G gene polymorphism is associated with the breast cancer susceptibility in Asians. However, more studies on the relationship between GSTP1 A/G gene polymorphism and the risk of breast cancer should be performed in further.     

Association of genetic polymorphisms in glutathione S-transferases and susceptibility to head and neck cancer

Polymorphism in glutathione S-transferase (GST) genes (GSTM1, GSTT1 and GSTP1) and interaction with environmental factors such as tobacco (smoking or chewing) and alcohol on susceptibility to head and neck squamous cell carcinoma (HNSCC) was studied in a case-control study. The study group consisted of 175 patients suffering from HNSCC and 200 age matched healthy controls. Statistical analysis showed an increase in risk to HNSCC in the patients with null genotype of GSTM1 (OR: 2.02; 95% CI: 1.32-3.10; P=0.001) or GSTT1 (OR: 1.66; 95% CI: 1.02-2.69; P=0.04), though the risk was not found to be significant when adjusted for age, sex, smoking, tobacco chewing or alcohol use by multivariate logistic regression model. Our data further showed that combination of deletion genotypes of GST (GSTM1 and GSTT1) confer an even higher risk of HNSCC. Interestingly, GSTP1 wild type genotype in combination with GSTM1 null or GSTT1 null genotype increased susceptibility for HNSCC (OR: 2.49 and 2.75, respectively). Likewise a much greater risk for HNSCC was observed in the patients carrying a genotype combination of GSTM1 null, GSTT1 null and GSTP1 (Ile/Ile) (OR: 4.47; 95% CI: 1.62-12.31; P=0.002). Our data have further provided evidence that tobacco chewing and alcohol consumption are the important risk factors for HNSCC. The interaction between tobacco chewing and null genotype of GSTM1 or GSTT1 resulted in about 3.5- and 2.2-fold increase in the risk respectively in the patients when compared to those not chewing tobacco. Alcohol use resulted in more than 4-fold increase in the risk in the patients with null genotype of GSTM1 as compared to those who are non-drinkers. Alcohol consumption also increased the risk (approx. 3-fold) in the cases with null genotype of GSTT1, though the association was not found to be significant when compared to non-drinkers. Our data have provided evidence that GST polymorphism modifies the susceptibility to HNSCC and have further demonstrated importance of gene-environment interaction in modulating the risk to HNSCC.     

A meta-analysis of the relationship between glutathione S-transferases gene polymorphism and hepatocellular carcinoma in Asian population

The results from the published studies on the association between glutathione S-transferases (GST) gene polymorphism and hepatocellular carcinoma (HCC) in Asian population are still conflicting. GSTM1, GSTT1 and GSTP1 are the mainly mutant sites reported at present. This meta-analysis was performed to evaluate the relationship between GST gene polymorphism and HCC risk in Asians. Association studies were identified from the databases of PubMed, Embase, Cochrane Library and CBM-disc (China Biological Medicine Database) on February 1, 2012, and eligible investigations were synthesized using meta-analysis method. Results were expressed with odds ratios (OR) for dichotomous data, and 95?% confidence intervals (CI) were also calculated. Twenty-five investigations were identified for the analysis of association between polymorphic deletion of GSTM1 and HCC, consisting of 3,547 patients with HCC and 6,132 controls. There was a marked association between GSTM1 null genotype and HCC susceptibility (OR 1.48, 95?% CI 1.19–1.85, P?=?0.0004). GSTM1 null genotype was associated with HCC risk in Chinese. Furthermore, null genotype of GSTT1 was associated with HCC susceptibility in Asians. For the GSTM1–GSTT1 interaction analysis, the dual null genotype of GSTM1/GSTT1 was significantly associated with HCC susceptibility in Asian population. However, GSTP1 ile105?val gene polymorphism was not associated with HCC risk in Asian population. In conclusion, GSTM1/GSTT1 null genotype is associated with the HCC susceptibility. However, GSTP1 gene polymorphism is not associated with HCC risk.     

Glutathione S-transferase M1, T1, and P1 polymorphisms and thyroid cancer risk: A meta-analysis

Glutathione S-transferases (GSTs) genetic variants have been explored extensively as a predictive factor for cancer etiology. This meta-analysis aimed to examine the associations GSTM1, GSTT1, and GSTP1 genetic polymorphisms with thyroid cancer risk. PubMed, EMBASE, Cochrane Library, and HuGNet database were searched up to November 2011 using the appropriate terms. Twelve studies regarding GSTM1 null polymorphism (1569 cases and 2907 controls), 11 studies concerning GSTT1 null polymorphism (1515 cases and 2863 controls), and 8 studies on GSTP1 Ile105Val (965 cases and 1604 controls) were included in the meta-analysis. The random effects odds ratio was 1.07 (95% CI: 0.88–1.31; I² = 54.1%, P for heterogeneity = 0.013) for the GSTM1 null vs. present genotype and 1.08 (95% CI: 0.75–1.57; I² = 81.4%, P for heterogeneity < 0.001) for the GSTT1 null vs. present genotype, and 1.02 (95% CI: 0.70–1.49; I² = 74.6%, P for heterogeneity < 0.001) for the GSTP1 Val/Val + Val/Ile vs. Ile/Ile genotype. Similarly, no significant associations were demonstrated for subgroup analyses performed by ethnicity and histological type. In conclusion, these three polymorphisms are unlikely to be major determinants of susceptibility to thyroid cancer. Reasons for potential heterogeneity of effects, which could include true biologic heterogeneity, publication bias, or chance, deserve further investigation. The relationship between these three genes and thyroid carcinoma must be evaluated further with gene–gene and gene–environment interactions.     

Association of genetic polymorphisms of glutathione-S-transferase genes (GSTT1, GSTM1, and GSTP1) and susceptibility to nonalcoholic fatty liver disease in Zahedan, Southeast Iran

Oxidative damage is thought to play a pivotal role in the pathogenesis of nonalcoholic fatty liver disease (NAFLD). Glutathione-S-transferases (GSTs) are involved in cell protection against oxidative stress. We examined whether GSTM1, GSTT1, and GSTP1 polymorphisms are associated with NAFLD in a sample of the Iranian population. The current case-control study included 83 patients with NAFLD and 93 healthy subjects. The GSTM1 and GSTT1 polymorphisms were analyzed by multiplex polymerase chain reaction (PCR). The GSTP1 polymorphism was detected by tetra amplification refractory mutation system-PCR assay. The GSTM1-null genotype was significantly associated with the development of NAFLD (odds ratios [OR]=2.171, 95% confidence intervals [CI]=1.188-3.970, p=0.015). The GSTP1 Val allele was shown to be a risk factor for NAFLD (OR=1.739, 95% CI=1.089-2.777, p=0.024). The GSTT1 polymorphism was not significantly different between control and patient groups (p=0.221). This study showed that GSTM1 and GSTP1, but not GSTT1, genetic polymorphisms are associated with NAFLD in a sample of the Iranian population, and may be used to determine the risk of development of NAFLD.     

Significant association between GSTT1 null genotype and susceptibility to pancreatic cancer

Many studies have investigated the association between glutathione S-transferase T1 (GSTT1) polymorphism and risk for pancreatic cancer, but those studies have yielded contradictory findings on the association. We performed a comprehensive search in the PubMed, EMBASE, and the Chinese National Knowledge Infrastructure databases to identify relevant studies. A meta-analysis was performed to examine the association between GSTT1 polymorphism and susceptibility to pancreatic cancer by calculating the pooled odds ratios (ORs) and corresponding 95 % confidence intervals (95 % CIs). Eight studies involving a total of 4,437 individuals were included. Overall, significantly increased pancreatic cancer risk was associated with GSTT1 null genotype when all studies were pooled into the meta-analysis (random effects OR = 1.61, 95 % CI 1.06–2.44; P = 0.025). Significantly increased risk of pancreatic cancer was also found for GSTT1 null genotype in Asians when stratified by ethnicity (fixed effects OR = 2.67, 95 % CI 1.74–4.09; P < 0.001). The findings demonstrate that GSTT1 null genotype have a modest effect on the genetic susceptibility to pancreatic cancer, and GSTT1 null genotype is associated with increased risk of pancreatic cancer.     

A meta-analysis of the relationship between glutathione S-transferase T1 null/presence gene polymorphism and the risk of lung cancer including 31802 subjects

The relationship between glutathione S-transferase T1 (GSTT1) null/presence gene polymorphism and the risk of lung cancer from the published reports are still conflicting. This study was conducted to evaluate the relationship between GSTT1 null/presence gene polymorphism and the risk of lung cancer using meta-analysis method. The association studies were identified from PubMed, and Cochrane Library on July 1, 2012, and eligible investigations were included and synthesized using meta-analysis method. 51 reports were recruited into this meta-analysis for the association of null genotype of GSTT1 with lung cancer susceptibility, consisting of 15,140 patients with lung cancer and 16,662 controls. There was a marked association between GSTT1 null genotype and lung cancer risk in overall populations (OR = 1.15, 95 % CI 1.04–1.27, P = 0.007). Furthermore, GSTT1 null genotype was associated with the lung cancer risk in Asians (OR = 1.47, 95 % CI 1.23–1.76, P < 0.0001). However, GSTT1 null genotype was not associated with the risk of lung cancer in Caucasians, Brazilian population and Africans. In conclusion, GSTT1 null genotype is associated with the lung cancer in overall populations and in Asians.     

The glutathione S-transferase M1 and P1 polymorphisms and rheumatoid arthritis: a meta-analysis

The aim of this study was to determine whether the Glutathione S-transferase M1 (GSTM1) and P1 (GSTP1) polymorphisms confer susceptibility to rheumatoid arthritis (RA). Meta-analysis was performed on the associations between the GSTM1 and GSTP1 null genotypes and RA, and on the association between smoking or seropositive status and the GSTM1 null genotype in RA patients. Twelve studies involving 3,990 RA patients and 2,815 controls were included in the meta-analysis. All 12 studies examined the GSTM1 polymorphism and three the GSTP1 polymorphism. Meta-analysis of GSTM1 null polymorphism in 2,291 RA and 2,713 control subjects revealed no association between RA and the GSTM1 null genotype (OR?=?1.139, 95?% CI?=?0.914–1.419, p?=?0.246). Stratification by ethnicity indicated no association between the GSTM1 null genotype and RA in Asians or Europeans (OR?=?1.245, 95?% CI?=?0.729–2.124, p?=?0.422; OR?=?1.023, 95?% CI?=?0.794–1.318, p?=?0.863). Furthermore, there was no association between smoking and the GSTM1 null genotype (OR?=?0.943, 95?% CI?=?0.734–1.210, p?=?0.642). In addition, no association was found between seropositive status including anti-CCP (anti-citrullinated antibody) and/or RF (rheumatoid factor) and the GSTM1 null genotype. Meta-analysis of 915 RA and 1,082 controls revealed no association between RA and the GSTP1 null genotype (OR?=?0.965, 95?% CI?=?0.802–1.161, p?=?0.704). Furthermore, stratification by ethnicity indicated no association between the GSTP1 null genotype and RA in Europeans (OR?=?0.794, 95?% CI?=?0.594–1.061, p?=?0.119). This meta-analysis suggests that the GSTM1 and GSTP1 polymorphisms are not associated with the risk of RA. However, due to the small number of studies included and our inability to perform subgroup analysis by environmental factors, further studies are required to explore the roles played by GSTM1 and GSTP1 polymorphisms in the pathogenesis of RA.     

Polymorphisms of the CYP1A1 and GSTM1 genes in relation to individual susceptibility to lung carcinoma in Chinese population.

Cytochrome P450 1A1 (CYP1A1) and glutathione S-transferase M1 (GSTM1) metabolize tobacco-related carcinogens. To investigate the prevalence of CYP1A1 and GSTM1, and their association with increased risk of lung carcinoma in Chinese, allele-specific PCR and multiplex PCR technique were employed to identify the genotypes of CYP1A1 and GSTM1 in a case-control study of 106 lung carcinoma patients with histopathological diagnosis and 106 matched controls free of malignancy in Jiangsu Province, China. Logistic regression analysis was performed to calculate the odds ratio (OR) and 95% confidence intervals (CI). The results showed that individuals with GSTM1 null, and the combined GSTM1 null/CYP1A1 Ile/Val or GSTM1 null/CYP1A1 Val/Val had an elevated risk of lung carcinoma, with the OR, 1.92 (P=0.02; CI, 1.07-3.46), 3.27 (P=0.01; CI, 1.23-8.84) and 9.33 (P=0.04; CI, 1.01-217.42), respectively. Light smokers (<30 pack-years) carrying GSTM1 null genotype were shown to have the increased risk to lung carcinoma (OR=3.47; CI, 1.13-7.57). Our study suggested that the null GSTM1 genotype, independently or in combined with at least one Val allele of CYP1A1, might affect the genetic susceptibility for lung carcinoma in Chinese population.     

Genetic Polymorphisms of GSTM1, GSTT1, and GSTP1 with Prostate Cancer Risk: A Meta-Analysis of 57 Studies

Background and Objectives

The 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.

Methods

Published 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.

Results

Fifty-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.

Conclusions

Our 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.