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The association of glutathione S-transferase (GST) enzymes with vitiligo is inconclusive. To evaluate tissue expressions of GST isoenzymes in vitiligo patients and to compare these expressions with healthy controls, we used 26 active depigmented patches on the trunk of vitiligo patients and 20 healthy sex and age matched controls. Punch biopsies were taken from the lesioned or normal skin. Tissue expression of GST isoenzymes were analyzed immunohistochemically. Tissue expression of GSTT1, GSTA1 and GSTP1 was significantly higher in the patient group than controls. Tissue expression of GSTM1 was not significantly different between the two groups. The increased tissue expression of GSTT1, GSTA1 and GSTP1 may represent a response to excess free radical formation in vitiligo and may support the role of oxidative stress in the pathogenesis of vitiligo. WOS:000698255600001 2-s2.0-85115232607 PubMed: 34547977

In developed countries, sudden infant death syndrome (SIDS) is the leading cause of death in infants in their first year of life. The risk of SIDS is increased if parents smoked during pregnancy and in presence of the child. Glutathione S-transferases (GSTs) catalyse the conjugation of glutathione with electrophilic compounds and toxins, making them less reactive and easier to excrete. As a gene dose effect was observed forGSTM1andGSTT1, the aim of this study was to investigate whether there is a connection between homozygous or heterozygous gene deletions ofGSTM1orGSTT1and the occurrence of SIDS. We found that heterozygous deletion ofGSTM1occurred significantly more frequently in the SIDS case group compared to the control group. A homozygous deletion ofGSMT1was slightly more frequently in the control group. A homozygous gene deletion ofGSTT1showed no significant difference between the SIDS group and the control group. We also found that in the SIDS group, the number of victims that were exposed to cigarette smoke was significantly higher than the number of victims without cigarette smoke exposure and that the mean lifetime of children whose mothers smoked was shorter in comparison with non-smoking mothers. In SIDS cases with homozygous gene deletions ofGSTM1, the median life span of children with tobacco smoke exposure was 60 days shorter than without smoke exposure. In conclusion, the absence of these two genes is not the only trigger for SIDS but could be a critical aspect of SIDS aetiology, particularly in SIDS cases with smoking parents.

Various types of toxic xenobiotic and electrophilic compounds, which were formed from the glutathione S-transferases cell metabolism and the oxidation stress, are the group enzymes with detoxification roles that are involved in the metabolism phase II. During the GSTM1 and GSTT1 gene homozygous deletion, the above enzymes completely lose their activity and consequently somatic mutation is formed. Furthermore, it is considered that it might have increased the risk of cancer. Therefore, the research works which connected the GSTMI and GSTTI gene deletion with the cancer of kidney, lung, prostate, breast, stomach, esophagus, large and narrow intestines. In this study, two gene deletion distribution is detected for cancer patients. We collected the blood samples of 60 patients who have been diagnosed with cancer. The DNA was extracted and the GSTM1 and GSTT1 genes were amplified using multiplex PCR. According to our research, the above two gene deletion is predominant among patients who have cancer. The results showed that from the total 60 patients GSTM1 and GSTT1 both deletions, GSTM1 gene deletion - 35%, GSTM1 gene deletion - 25%, GSTT1 gene deletion - 26.7%, GSTM1 and GSTT1 both positive -13.3 %. Therefore, we think that in order to prevent tumor and cancer, these gene mutations must be revealed and it is important to bring the risky group under medical control and assist them in order to prevent them from this disease.

Serous ovarian cancer (SOC) is the most common women cancer and the leading cause of cancer-related mortality among the gynaecological malignancies. Although effective chemotherapeutics combined with surgery are developed for the treatment, the five-year survival rate is unsatisfactory due to chemoresistance. To overcome this shortcoming of chemotherapy, we established taxol and carboplatin resistant SOC cell lines for the understandings of the molecular and cellular mechanisms of chemoresistance. Here, we found that these chemoresistant cell lines showed less viability and proliferation, due to more cells arrested at G0/G1 phase. Glutathione-S-transferases-theta1 (GSTT1) was significantly upregulated in these chemoresistant cells, along with other chemoresistant genes. Meanwhile, GSTT1 expression was also significantly upregulated in the SOC patient tissues after taxol treatment, indicating this upregulation was physiologically relevant to chemotherapy. Further, suppression of GSTT1 expression by shRNA in SOC cell lines led to more sensitivity to drug treatment, through increasing divided cells and promoting cell death. Moreover, the expression of DNA topoisomerase 1 (Topo I) was in synergy with that of GSTT1 in the chemoresistant cells, and GSTT1 can bind to Topo I in vitro, which suggested GSTT1 could function through DNA repair mechanism during chemoresistance. In summary, our data imply that GSTT1 may be a potential biomarker or indicator of drug resistance in serous ovarian cancer.

BackgroundThalassemia, a monogenic genetic disease of red blood cells, is spread widely throughout the world. Glutathione S transferase (GST) enzymes have an antioxidant role in detoxification processes of toxic substances This study aimed to determine the role of the genetic modifier genes GSTT1 and GSTM1, and the catalase (CAT) gene in clinical degrees of hemoglobin (Hb)E/β thalassemia. MethodsSixty HbE/β Thalassemia patients were examined to determine their clinical pictures. Clinical score was based on age when thalassemia symptoms appeared, time of diagnosis, time of first blood transfusion, pre-transfusion hemoglobin concentration, frequency of transfusions, and enlargement of spleen. Ferritin concentration was also obtained from medical records. Gene polymorphisms of GSTT1, GSTM1, and CAT were measured using PCR and PCR-RFLP methods. Clinical scores were categorized into mild (0-3.5), moderate (4-7), and severe (7.5-10) degrees, while ferritin level was expressed in mg/dL. One way Anova was used to analyze the data. ResultsThe clinical appearance showed that severe, moderate, and mild degrees accounted for 42%, 45%, and 13%, respectively. The majority had a high ferritin level of more than 5000 mg/dL (67%). GSTT1 null, GSTM1 null, and CAT minor allele genotypes were 21.7%, 33.3%, and 12.1%, respectively. GSTT1, GSTM1, and CAT genotypes had no impact on the severity of thalassemia patients (p=0.091, p=0.082, and p=0.141, respectively).ConclusionGSTT1, GSTM1, CAT gene polymorphisms tend to be a minor aspect of severity of clinical outcome for HbE/â thalassemia patients and should be not considered a routine laboratory check.

Over the past four decades, patients with advanced ovarian cancer (OC) has enjoyed greatly improved survival rate considering advances in combined chemotherapy with platinum and paclitaxel. We investigated the association between polymorphisms within glutathione S-transferase genes (GSTM1, GSTT1 and GSTP1) and short- and long-term efficacy of concurrent chemoradiotherapy (CCRT) in advanced OC. Patients with advanced OC and healthy females were selected in our study. Multiplex polymerase chain reaction (PCR) and PCR-restriction fragment length polymorphism (PCR-RFLP) were applied to detect homozygous deletions in GSTM1 and GSTT1, as well as codon 105 genetic polymorphisms in GSTP1 exon 5. All the patients with advanced OC were treated with CCRT. Toxicity of chemotherapy, short-term efficacy, recurrence and metastasis, respectively. Long-term survival outcomes were checked with a further examination and all patients were followed up for three years after CCRT.Compared with healthy females, patients with advanced OC showed higher frequencies of GSTT1 non-null genotype and homozygous mutation type GG of GSTP. GSTP1genetic polymorphisms were relevant to neutropenia resulted from CCRT in patients with advanced OC. Compared with patients with GSTT1non-null genotype, those with GSTT1 null genotype appeared to enjoy a better short-term efficacy, lower recurrence and metastasis rate, higher survival rate and longer mean survival time. Compared with patients with GG genotype, those with GSTP1 AA + AG genotype also enjoyed more positive results. Our results reveal that GSTT1 null genotype and GSTP1AA + AG genotype are associated with short- and long-term efficacy of CCRT in advanced OC.

Despite the toxicity and health risk characteristics of formaldehyde (FA), it is currently used as a cytological fixative and the definition of safe exposure levels is still a matter of debate. Our aim was to investigate the alterations in both oxidative and inflammatory status in a hospital working population. The 68 workers recruited wore a personal air-FA passive sampler, provided a urine sample to measure 15-F2t-Isoprostane (15-F2t-IsoP) and malondialdehyde (MDA) and a blood specimen to measure tumour necrosis factor α (TNFα). Subjects were also genotyped for GSTT1 (Presence/Absence), GSTM1 (Presence/Absence), CYP1A1 exon 7 (A &gt, G), and IL6 (−174, G &gt, C). Workers were ex post split into formalin-employers (57.3 μg/m3) and non-employers (13.5 μg/m3). In the formalin-employers group we assessed significantly higher levels of 15-F2t-IsoP, MDA and TNFα (&lt, 0.001) in comparison to the non-employers group. The air-FA levels turned out to be positively correlated with 15-F2t-IsoP (p = 0.027) and MDA (p &lt, 0.001). In the formalin-employers group the MDA level was significantly higher in GSTT1 Null (p = 0.038), GSTM1 Null (p = 0.031), and CYP1A1 exon 7 mutation carrier (p = 0.008) workers, compared to the wild type subjects. This study confirms the role of FA in biomolecular profiles alterations, highlighting how low occupational exposure can also result in measurable biological outcomes.

Coronavirus disease 2019 (COVID‐19) caused by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection has become a global health issue and develops into a broad range of illnesses from asymptomatic to fatal respiratory diseases. SARS‐CoV‐2 infection is associated with oxidative stress that triggers cytokine production, inflammation, and other pathophysiological processes. Glutathione‐S‐transferase (GST) is an important enzyme that catalyzes the conjugation of glutathione (GSH) with electrophiles to protect the cell from oxidative damage and participates in the antioxidant defense mechanism in the lungs. Thus, in this study, we investigated the role of GSTM1 and GSTT1 gene polymorphism with COVID‐19 susceptibility, as well as its outcome. The study included 269 RT‐PCR confirmed COVID‐19 patients with mild (n = 149) and severe (n = 120) conditions. All subjects were genotyped for GSTM1 and GSTT1 by multiplex polymerase chain reaction (mPCR) followed by statistical analysis. The frequency of GSTM1−/−, GSTT1−/− and GSTM1−/−/GSTT1−/− was higher in severe COVID‐19 patients as compared to mild patients but we did not observe a significant association. In the Cox hazard model, death was significantly 2.28‐fold higher in patients with the GSTT1−/− genotype (p = 0.047). In combination, patients having GSTM1+/+ and GSTT1−/− genotypes showed a poor survival rate (p = 0.02). Our results suggested that COVID‐19 patients with the GSTT1−/− genotype showed higher mortality.

Glutathione S-transferases (GSTs) are the family of enzymes involved in the second line of defense against oxidative stress (OS). The lack of GSTT1/GSTM1 enzyme quantity or activity, due to the presence of homozygous deletion compromises antioxidative defense resulting in OS. OS is the critical mechanism in the pathophysiology of atherosclerosis, coronary artery disease, and myocardial infarction (MI). The increase in reactive oxygen species together with the process of apoptosis plays a role in left ventricular remodeling (LVR) after MI. The associations of GSTT1 and GSTM1 gene polymorphisms with the risk of MI are inconsistent. The aim was to analyze the association of GSTT1/GSTM1 null genotypes with first MI and LVR 8 months after the MI. The study involved 330 controls and 438 consecutive patients with symptoms and signs of first MI. The subgroup of 150 MI patients was prospectively followed up for 6 months. Evidence of maladaptive LVR was obtained by 2D Doppler echocardiography 3–5 days and 6 months after the MI. A multiplex polymerase chain reaction was used to detect the deletion in GSTT1 and GSTM1 genes. GSTM1 null genotype was significantly and independently associated with first MI (adjusted OR = 1.45 95% CI 1.03–2.03, p = 0.03). Association of double null genotypes with maladaptive LVR in patients 6 months after the first MI was no longer significant after adjustment for factors that differed significantly between patients with and without maladaptive LVR. This study demonstrated the association of GSTM1 null genotypes with the risk of MI in the Serbian population.

Objective Glutathione S-transferases have been associated with experimental resistance to some drugs. The present study investigated the factors associated with blood pressure control in patients with essential hypertension, especially the role of GSTT1 and GSTM1 genes polymorphisms. This cross-sectional study in Burkina Faso consisted of 200 patients with essential hypertension and under treatment. Results In the present study, 57.5% (115/200) of patients had their hypertension under control. No statistically significant difference was found between controlled and uncontrolled groups for anthropometric and biochemical parameters as well as for GSTT1 or GSTM1 gene polymorphisms (all p > 0.05). Current alcohol consumption (OR = 3.04; CI 1.88–6.13; p p p p

Simple Summary Epidemiological studies have shown that individual susceptibility to cancer is mediated by genetic and environmental factors. The aim of the present study is to evaluate the individuals’ metabolic genetic susceptibility to toxic habits (smoking and alcohol consumption) by detecting polymorphisms CYP1A1 rs1048943 T>C and CYPA1A2 rs4646903 A>G, and null polymorphisms in GSTM1 and GSTT1 genotypes, comparing a group of healthy control subjects with a population of larynx cancer patients from southeastern Spain. As results patients with larynx cancer present more gene GSTM1 and GSTT1 null polymorphisms, and CYP1A1 rs4646903 T>C polymorphisms. Abstract Background: some types of cancer have been associated with the presence of single nucleotide polymorphisms (SNPs) of some genes that encode enzymes: glutathione-S transferase (GST), whose alteration leads to loss of function and a lower capacity to eliminate toxic GSTM1 and GSTT1 null genotypes; SNPs causing loss of function of CYP1A1 or CYP1A1–2 cytochrome P450 enzymes related with a lower capacity to deactivate hydrocarbons related to smoking, which involves a higher risk of developing some smoking-dependent cancers including larynx cancer. Objective: to compare the presence of null SNPs in genes GSTM1, GSTT1, and CYP1A1 rs 4646903 T>C, and CYP1A1–2 RS1048943 A>G in patients with hypopharyngeal and larynx cancer with a healthy control group. Materials and method: The study included a total of 80 patients with hypopharyngeal and laryngeal cancer and 23 healthy subjects. Genomic DNA was obtained from saliva samples, determining genotype GSTM1 (present +, or null −), GSTT1 (present + or null −). Polymorphisms (SNP) in CYP1A1 T>C (present + CC, or absent − TC/TT), and CYP1A1–2 A>G (present + GG, or absent − AG/AA). Results: the mean age of patients with larynx cancer was 62 years and of control subjects 63 years. Of the total sample, over 95% were men, and over 90% were smokers. The presence of null genotypes for GTM1 was 50% in patients with larynx cancer (p = 0.042), while GSTT1 was 88.75% (p = 0.002). CYP1A1 rs4646903 T>C polymorphisms were detected in 100% of cases of larynx cancer and 17.39% of healthy subjects (p > 0.001). Conclusions: patients with larynx cancer present more gene GSTM1 and GSTT1 null polymorphisms, and CYP1A1 rs4646903 T>C polymorphisms.

Background. The presence or absence of glutathione S-transferase M1 gene (GSTM1) and glutathione S-transferase T1 gene (GSTT1) polymorphisms, and their combined effects have been suggested as a risk factor for colorectal cancer (CRC). However, the results are inconsistent. Objectives. An updated meta-analysis was performed to solve the controversy. Methods. Meta-analyses of Observational Studies in Epidemiology (MOOSE) guidelines were used. Results. Overall, the GSTM1 null genotype was associated with an increased CRC risk in Caucasians (odds ratio (OR) = 1.14, 95% confidence interval (CI): 1.05–1.23), Asians (OR = 1.19, 95% CI: 1.08–1.32), high-quality studies (OR = 1.12, 95% CI: 1.06–1.18). Moreover, the GSTM1 null genotype was also associated with an increased colon cancer risk (OR = 1.32, 95% CI: 1.16–1.51). The GSTT1 null genotype was also associated with an increased CRC risk in Asians (OR = 1.08, 95% CI: 1.02–1.15) and Caucasians (OR = 1.24, 95% CI: 1.09–1.41). Moreover, The GSTT1 null genotype was associated with an increased rectal cancer risk (OR = 1.13, 95% CI: 1.01–1.27, I2 = 8.3%) in subgroup analysis by tumor location. Last, the GSTM1 null/GSTT1 null genotype was associated with an increased CRC risk in Asians. Conclusion. This meta-analysis indicates that the GSTM1 and GSTT1 null genotypes are associated with increased CRC risk in Asians and Caucasians, and the GSTM1 null/GSTT1 null genotype was associated with increased CRC risk in Asians.

Background Prenatal exposure to polycyclic aromatic hydrocarbons (PAH) has been linked to allergic disease onset. Variations in the glutathione S-transferase (GST) gene family can impact the progression of allergic diseases. We sought to examine the association between prenatal PAH exposure and infantile allergic diseases in 6-month-old infants, and how maternal glutathione S-transferase M1 (GSTM1) or T1 (GSTT1) polymorphism affects the association between prenatal PAH exposure and allergic diseases in the Mothers and Children's Environmental Health (MOCEH) study. Methods The study sample comprised 349 infants and their mothers from the MOCEH study, for whom 1-hydroxypyrene (1-OHP) and 2-naphthol were measured in both the early period of pregnancy and late period of pregnancy. An infant was deemed to be affected by an allergic disease if diagnosed with or if developed at least one of the allergic diseases. A logistic regression analysis was performed to study the association between urinary 1-OHP and 2-naphthol levels during pregnancy and allergic diseases in 6-month-old infants. Furthermore, analyses stratified by maternal GSTM1 or GSTT1 present/null polymorphisms were performed. Results The risk of allergic diseases in 6-month-old infants was significantly increased in accordance with an increase in urinary 1-OHP during the early period of pregnancy (odds ratio [OR]: 1.84; 95% confidence interval [CI]: 1.05, 3.23; by one log-transformed unit of 1-OHP μg/g creatinine). The increased risk of infantile allergic diseases associated with urinary 1-OHP during the early period of pregnancy was limited to the maternal GSTT1 null type (OR: 2.69; 95% CI: 1.17, 6.21, by one log-transformed unit of 1-OHP μg/g creatinine); however, the Relative Excess Risk due to Interaction was not statistically significant. Conclusions The present study found that infantile allergic diseases could be affected by intrauterine PAH exposure, particularly in the early prenatal period and the risk was limited to the maternal GSTT1 null type.

Objective: Glutathione S-transferase M1 and T1 (GSTM1 and GSTT1) are the key detoxification enzymes of xenobiotics, including chemotherapeutic drugs. The deletion polymorphisms of GSTM1 and GSTT1 genes are associated with reduced enzyme activity that influenced clinical outcomes of chemotherapeutic agents in breast cancer. However, there is limited information among Thai patients. This research aims to explore the frequency and role of GSTM1 and GSTT1 polymorphisms on survival among Thai patients with breast cancer. Methods: The retrospective cohort study was performed. Demographic data and clinicopathology characteristics were collected from hospital base registry data and medical records. A multiplex qualitative real-time PCR method was used to detect the presence or absence of the GSTM1 and GSTT1 gene in the genomic DNA samples of the participants. Results: The frequencies of the GSTM1 and GSTT1 null genotypes in 198 breast cancer patients were 65.70% and 33.30%, respectively. The overall survival at 1, 3 and 5 years were 95.00%, 83.00%, 71.00% respectively. The log rank test and Cox proportional hazards revealed a significant different in the 5-years overall survival according to lymph node metastasis and tumor stage (P = 0.014 and P < 0.001). No associations between overall survival and GSTM1 or GSTT1 genotype were found in single or combined genotypes analyses (P = 0.76 and P= 0.15). Conclusion: The results of our study provided the epidemiological information for prognostic of survival in breast cancer patients treated with chemotherapy.

Glutathione S-transferase (GST) enzymes are responsible for cellular detoxification of many carcinogens and are important anticancer elements. This study assessed potential relationships between GSTM1, GSTT1, and GSTP1 polymorphisms and colorectal cancer (CRC) risk in Polish nonsmokers. We also analyzed the influence of GST gene polymorphisms on CRC clinical and histopathological features. Our study included 197 CRC patients and 104 healthy controls. GSTM1, GSTT1, and GSTP1 polymorphisms were evaluated using qPCR. Polymorphism frequencies observed in our control group corresponded to those in other European populations. The GSTM1 null and GSTT1 null genotypes were observed with similar frequencies in both CRC patients and controls (GSTM1 null: 46.7% vs. 45.2%; GSTT1 null: 15.7% vs. 20.2%). GSTP1 Ile/Ile, Ile/Val, and Val/Val genotype frequencies were respectively 42.1%, 48.2%, and 9.6% in patients and 48.1%, 42.3%, and 9.6% in controls. GSTT1 polymorphism correlated with higher tumor grade in CRC patients, and the GSTM1 null/null genotype was associated with more frequent metastasis to lymph nodes (pN classification). Our results suggest that GST gene polymorphisms may influence CRC tumor grade and stage.

Endometriosis is a gynecological disease defined by the histological presence of endometrial glands and stroma outside the uterine cavity. Ectopic endometrial cell proliferation and chronic inflammation in endometriosis were shown to be associated with oxidative stress (OS) induction. OS is a condition in which reactive oxygen species (ROS) overproduction and antioxidant deficiency cause a shift in oxidant/antioxidant balance. Glutathione S-transferases (GSTs) comprise a family of eukaryotic and prokaryotic phase II metabolic isozymes best known for their ability to catalyze the conjugation of the reduced form of glutathione (GSH) to xenobiotic substrates for the purpose of detoxification. The aim of this project was to study the concentrations of GSTT1 in the serum and peritoneal fluid (PF) of patients with different stages of endometriosis. Frothy two PF and serum from normal and 152 from different stages of patients with endometriosis (stage I: n = 30, stage II: n = 39, stage III: n = 43 and stage IV: n = 40) were included in this study. The level of GSTT1 in the serum was determined by enzyme linked immunosorbent assay (ELISA). The results showed the presence of GSTT1 in all serum and peritoneal fluid samples, while, starting from stages I to IV endometriosis, a significant decrease in GSTT1 concentration was seen as compared to controls. It is concluded that levels of GSTT1 is negatively correlated with advanced stages of endometriosis. It is also suggested that the detection of serum and/or peritoneal fluid GSTT1 concentration may be valuable in the classifying of endometriosis.

Background. Genetic factors cause 30-50 % of cases of male infertility different forms. We have conducted the investigation of the lipid peroxidation and antioxidant protection system components, associated with the biotransformation genes polymorphisms, in men with infertility. Aims: to study parameters of lipid peroxidation and antioxidant defense system associated with polymorphisms of biotransformation genes in infertile Mongoloid men. Materials and methods. The main group included 143 men of reproductive age from Mongoloid population who came to the Public Health Institution "Republican Perinatal Center" in Ulan-Ude with the problem of one year and more infertility after the marriage. Fifty-three almost healthy males with proven fertility were included in the control group. Blood samples of all men were genotyped by glutathione S-transferase (GSTP1, GSTM1, GSTT1) gene family and activity of glutathione system enzymes was determined. Results. In the fertile Mongoloids with non-functional genotype GSTT1(0/0)/GSTM1(0/0) we have established an increase concentration of a-tocopherol in serum, activity of glutathione peroxidase and a decrease in glutathione-S-transferase, as well as a decrease in the concentration of a-tocopherol. In infertile Mongoloids with non-functional GSTT1(0/0)/ GSTM1 (0/0) genotypes, an increase in the tiobarbituric acid reactants, glutathione peroxidase and a decrease in the concentration of a-tocopherol was found in the ejaculate; we also detected a decrease in the concentration of a-tocopherol, the level of oxidized glutathione and glutathione-s-transferase activity. Conclusions. Genetically determined peculiarities of functioning of the xenobiotic biotransformation system make each individual unique with regard to their adaptive capacity - resistance or sensibility to the damaging exo- and endogenous factors.

// Jian Zhang 1, * , Ying Wu 1, * , Xichun Hu 1 , Biyun Wang 1 , Leiping Wang 1 , Sheng Zhang 1 , Jun Cao 1 and Zhonghua Wang 1 1 Department of Medical Oncology, Fudan University Shanghai Cancer Center, Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China * These authors have contributed equally to this work Correspondence to: Zhonghua Wang, email: zhonghuawang95@hotmail.com Keywords: GSTT1; GSTP1; GSTM1; polymorphism; metastatic breast cancer Received: December 12, 2016 Accepted: August 29, 2017 Published: November 14, 2017 ABSTRACT Purpose: 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). Patients and Methods: 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. Results: 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. Conclusion: 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.

The aim of this research was to investigate the glutathione system components and their association with polymorphisms GST genes in men with infertility. Materials and Methods: One hundred and sixty Russian men of reproductive age (Caucasians) who came to the public health institution Republican Perinatal Center in Ulan-Ude with an infertility problem of one year and more after marriage were included in the main group. The control group included 104 men with proven fertility. DNA samples were genotyped for polymorphisms in GSTP1, GSTT1 and GSTM1genes and activity of glutathione system enzymes was determined. Results: The most informative genetic and metabolic indicators in Caucasian males with infertility were combinations of the null genotypes GSTT1(*0/*0)+GSTM1(*0/*0) associated with a decrease of GST activity in blood and ejaculate and an increase of GSH and GPO in the blood. Another combination is GSTP1(Ile105Val)+GSTP1(Ala114Val), which is associated with suppression of the blood and ejaculate GPO activity and a decrease in blood concentration of GSH.

Aim of work: To study the genetic variants of glutathione S-transferases and monocyte CD64 expression in systemic lupus erythematosus patients and to evaluate their role in disease susceptibility, activity and damage. Patients and methods: Forty female SLE patients and 40 age matched controls were genotyped for GSTP1, GSTM1 and GSTT1 gene polymorphisms using polymerase chain reaction-restriction fragment length polymorphism, conventional PCR and were assessed for monocyte CD64 expression level using flow cytometry. SLE disease activity index (SLEDAI) and the systemic lupus international. collaborating clinics/damage index (SLICC DI) were considered. Results: The patients mean age was 28.13 ± 4.56 years and disease duration of 6.4 ± 4.9 with a SLEDAI of 14.4 ± 7.1 and SLICC/DI 3.7 ± 1.5. The frequency of GSTM1 null genotype tended to be higher (55%) in SLE patients compared to the controls (and 42.5%) (p = 0.09). The frequency of GSTT1 null genotype was significantly higher in SLE patients (25%) compared to controls (12.5%) (p

Backgraund . Tick-borne encephalitis (TBE), one of the large-scale public health problems of the Siberian region, can cause significant cytogenetic damage in humans by stimulating oxidative stress. Active functioning of the detoxification system including enzymes of glutathione-S-transferase is intended to protect the genetic structure of cells in the body, while at the same time, there are studies showing the defective functioning of this system in individuals with obesity. Aims . Aim of this work is to study the longevity of term of TBE-induced cytogenetic damage in patients with different alleles of genes of glutathione-S-transferase, suffering from alimentary-constitutional obesity compared with the control. Materials and methods . We were examined 133 female residents of the northern areas of Tomsk region from 35 to 44 years old who were hospitalized for infection TBE at local medical clinics. All individials were divided into two subgroups. Patients of the 1st subgroup (control) had a body mass index (BMI) within 21–26, the 2nd subgroup had BMI showing severe obesity (BMI 35–45). Buccal cells for cytogenetic and molecular analysis were taken several times: 1–2 days after hospitalization, 1 week, 1 month, 3 months, and 6 months after beginning of the disease. Methods of immunoassay and polymerase chain reaction (PCR) was used to confirm the diagnosis of TBE. As an untreated control were examined 126 healthy female residents of the same age groups. All individuals signed informed consent. In the analysis of deletions in the genes GSTM1 and GSTT1 was used multiplex PCR. We studied at least 1000 epithelial buccal cells from each individual. Results . In patients with high BMI rates revealed a significant increase in the frequency of the buccal cells with cytogenetic damage, compared to the control group. TBE disease was significantly increased the frequency of the cytogenetically damaged cells in this group of patients. The cytogenetic aberrations persisted in their body for six months after hospitalization. In patients with normal BMI rates TBE induced significantly less changes. The recovery of normal cytogenetic status was observed in this group 3 months after hospitalization. Analysis of the glutathione-S-transferase gene variants showed that in TBE patients with normal BMI and non-active alleles of these genesthe frequency of micronucleated epithelial cellswere significantly increased compared to the patients with the active GSTM1 (+) / GSTT1 (+)genes. In the patients with alimentary obesity such patterns were not observed. Conclusions . Thus,infection with TBE in patients with obesity induced significant increase in both the frequency of cytogenetically damaged cells and the longevity of their persistency in the body compared to these in control group. Polymorphisms in genes of glutathione-S-transferase had no significant effect on the indices.

// Ying Gao 1, * , Fei Gao 2, * , Ting-Ting Hu 3 , Gang Li 4 , Yan-Xia Sui 5 1 Department of Radiotherapy Oncology, First Affiliated Hospital of Medical College of Xi’an, Jiao Tong University, Xi’an, Shanxi, China 2 Department of Neurology, First Affiliated Hospital of Xi’an Medical University, Xi’an, Shanxi, China 3 Department of Medical, First Affiliated Hospital of Medical College of Xi’an, Jiao Tong University, Xi’an, Shanxi, China 4 Second Department of Thoracic Surgery, First Affiliated Hospital of Medical College of Xi’an, Jiao Tong University, Xi’an, Shanxi, China 5 Department of Pathology, First Affiliated Hospital of Medical College of Xi’an, Jiao Tong University, Xi’an, Shanxi, China * These authors contributed equally to this work and should be considered as co-first authors Correspondence to: Ying Gao, email: gaoyyingqw@163.com , togaoying@163.com Keywords: GSTM1, GSTT1, polymorphism, lung cancer, meta-analysis Received: September 14, 2016 Accepted: February 23, 2017 Published: March 06, 2017 ABSTRACT Many studies have reported an association between the glutathione S-transferase M1 null and T1 null polymorphisms and lung cancer risk. However, the combined effects of GSTM1 null and GSTT1 null polymorphisms have not been reported previously. We, therefore, performed a meta-analysis to investigate the combined effects. 40 publications with 44 case–control studies were selected in the meta-analysis, including 13,706 cases and 13,093 controls. Significant association was observed between the combined effects of GSTM1 and GSTT1 polymorphisms and lung cancer risk when all the eligible studies were pooled into the meta-analysis. When we performed subgroup analysis, significantly increased lung cancer risk was observed in Caucasians (− − vs. + + : OR = 1.23, 95% CI: 1.07 to 1.41), Asians (− − vs.− +: OR = 1.24, 95% CI: 1.10 to 1.41; recessive model: OR = 1.45, 95% CI: 1.19 to 1.77; dominant model: OR = 1.53, 95% CI: 1.24 to 1.90), Indians (− − vs. + + : OR = 2.53, 95% CI: 1.61 to 3.98; recessive model: OR = 1.69, 95% CI: 1.07 to 2.67; dominant model: OR = 2.11, 95% CI: 1.36 to 3.28), hospital-based studies, and population-based studies. In summary, this meta-analysis indicates that the combined effects of the GSTM1 and GSTT1 polymorphisms are associated with increased lung cancer risk in Asians, Caucasians, and Indians.

Background and Aim: Molecular epidemiology is an interdisciplinary field concerning the analysis of biological indicators and the investigation of individual DNA polymorphisms. The glutathione-S-transferases (GSTs) are one of the most studied metabolic gene families. They are involved in the genesis of oxidative stress and many authors hypothesize that some null polymorphic variants determine increasing toxic effects in tissues. Oxidative stress and antioxidant systems are very important in the onset and progress of glaucoma, one of the leading causes of blindness worldwide. We investigate the association of null variant of GST (M1 and T1) with the risk of primary open angle glaucoma (POAG) and we considered the ethical and legal implications of genetic procedures as a screening tool. Materials and Methods: We conducted a case-control study including 103 unrelated carriers of glaucoma in a southern Italian population (living in Eastern Sicily) and 150 unrelated healthy individuals as controls, whose buccal swabs samples were genotyped for GST polymorphisms using a standardized multiplex PCR based method. Results: In patients with glaucoma (primary open angle glaucoma, POAG) null genotype of the investigated genetic polymorphisms is very common compared to the healthy individuals. The obtained data suggest an influence of the (dual) null genotype on the normal metabolic pathway in the genesis of congenital glaucoma giving to these polymorphisms the role of so-called “indicators of susceptibility”. Conclusions: We conclude that the increased frequency of null GSTs (M1, T1) in patients with glaucoma could be considered a risk factor for incidence of the disease. Screenings can be carried out only in compliance with legislative rules. Keywords: Glaucoma; Glutathione S-transferase; GSTM1; GSTT1

The glutathione S-transferase (GST) genes encode enzymes that mediate the detoxification of xenobiotics by catalyzing the conjugation of glutathione (GSH) to xenobiotic substrates. The aim of the current study is to investigate the association between GSTT1 and GSTM1 polymorphisms and chronic myeloid leukemia (CML) among Sudanese patients. Patients with CML (n = 115) were recruited to the study from the Radiation and Isotope Centre Khartoum (RICK)-Sudan. Healthy individuals (n = 104) were included as controls. Genotyping of GSTT1 and GSTM1 polymorphisms was performed using multiplex PCR. Null deletions in the GSTT1 and GSTM1 genes are common in the Sudanese population (control group), with frequencies of 33.9% and 38.2%, respectively. The frequencies of GSTT1 (OR: 3.25, 95% CI: 1.87–5.65, p < 0.001) and GSTM1 (OR: 2.14, 95% CI: 1.25–3.67, p < 0.005) null genotypes were significantly higher in CML patients vs. controls. The distribution of GSTT1 and GSTM1 null polymorphisms was not different between male and female (p > 0.01) and young and old CML patients (p > 0.05). Hematological parameters were not affected by null polymorphisms in the patient group (p > 0.05). In addition, the frequency of GSTM1 null polymorphism was lower in advanced-phase CML patients compared to chronic-phase patients (p < 0.05). The GSTT1 and GSTM1 null polymorphisms are associated with CML among Sudanese patients, independently of their age and gender.

Oxidative stress and systemic inflammation are closely linked with increased risk of cancer development. Tumor necrosis factor alpha (TNF-α) is one of the pro-inflammatory cytokines. Glutathione S-transferases (GSTs) are enzymes involved in oxidative stress handling. Polymorphisms of genes encoding mentioned molecules may potentially influence the risk and the outcome in neoplastic diseases. Multiple myeloma (MM) is a hematological malignancy characterized by clonal, atypical plasma cell proliferation. In the present study we investigated the association of deletion polymorphisms in GSTT1/GSTM1 genes and single nucleotide polymorphisms (SNPs) in the TNF-α gene at positions −308/−238 with the risk and outcome in MM and sensitivity to bortezomib under in vitro conditions. One hundred newly diagnosed MM patients and 100 healthy blood donors were genotyped by means of multiplex PCR (for GSTs) and PCR-RFLP (for TNF-α). In a subgroup of 50 MM patients, bone marrow cells were treated with bortezomib in vitro. Patients with −238GA+AA or GSTT1-null genotypes had 2.0 (p = 0.002) or 2.29 (p = 0.013) fold increased risk of MM. The interaction effects and risk of MM were observed in GSTT1/GSTM1-null (OR = 2.82, p = 0.018), −308/−238GA+AA (OR = 5.63, p < 0.001), as well as in all combinations of −308 with GSTs. The −308/−238GA+AA genotypes in comparison to GG were associated with earlier MM onset−61.14 vs. 66.86 years (p = 0.009) and 61.72 vs. 66.52 years (p = 0.035), respectively. Patients with GSTM1-present had shorter progression-free-survival (15.17 vs. 26.81 months, p = 0.003) and overall-survival (22.79 vs. 34.81 months, p = 0.039) compared with GSTM1-null. We did not observe relationship between response rate and studied polymorphisms. The in vitro study revealed significantly higher number of apoptotic cells at 12 nM of bortezomib in GSTT1-present, GSTM1-null/present, −308GG and −238GG/GA+AA genotypes. Our findings comprise large analysis of studied polymorphisms in MM.

Introduction: Di-isocyanates TDI (toluene di-isocyanate), MDI (diphenylmethane di-isocyanate), and HDI (hexamethylene di-isocyanate) are the most common chemicals causing occupational asthma. Di-isocyanate inhalation has been reported to induce oxidative stress via reactive oxygen and nitrogen species leading to tissue injury. Glutathione transferases (GSTs) and N-acetyltransferases (NATs) are detoxifying enzymes whose general function is to inactivate electrophilic substances. The most important genes regulating these enzymes, i.e., GSTM1, GSTP1, GSTT1, NAT1, and NAT2 have polymorphic variants resulting in enhanced or lowered enzyme activities. Since inability to detoxify harmful oxidants can lead to inflammatory processes involving activation of bronchoconstrictive mechanisms, we studied whether the altered GST and NAT genotypes were associated with bronchial hyperreactivity (BHR) in patients with di-isocyanate exposure related occupational asthma, irrespective of cessation of di-isocyanate exposure, and adequacy of asthma treatment. Methods: Polymerase chain reaction (PCR) based methods were used to analyze nine common polymorphisms in GSTM1, GSTM3, GSTP1, GSTT1, NAT1, and NAT2 genes in 108 patients with diagnosed occupational di-isocyanate-induced asthma. The genotype data were compared with spirometric lung function and BHR status at diagnosis and in the follow-up examination on average 11 years (range 1–22 years) after the asthma diagnosis. Serum IgE and IL13 levels were also assessed in the follow-up phase. Results: An association between BHR and GSTP1 slow activity (Val105/Val105) genotype was demonstrated in the subjects at the follow-up phase but not at the diagnosis phase. Moreover, the patients with the GSTP1 slow activity genotype exhibited characteristics of Th-2 type immune response more often compared to those with the unaltered GSTP1 gene. Interestingly, all 10 patients with the GSTP1 slow activity genotype had both the GSTM3 slow activity genotype and the unaltered GSTP1 gene. Discussion: The results suggest associations of the low activity variants of the GSTP1 gene with BHR. The fact that these associations came up only at the follow-up phase when the subjects were not any more exposed to di-isocyanates, and used asthma medication, suggest that medication and environmental factors influence the presentation of these associations. However, due to the exploratory character of the study and relatively small study size, the findings remain to be confirmed in future studies with larger sample sizes.

Background: It is postulated that both individual genotype and environmental factors such as diet may modify the risk of developing colorectal cancer (CRC). The influences of GST gene polymorphism and red meat intake on CRC occurrence in the Polish population were analyzed in this study. Methods: Genotyping was performed with the qPCR method. Results: A high frequency of meat consumption was associated with an over 2-fold increase in the risk of colorectal cancer odds ratio (OR) adjusted for sex and age = 2.4, 95% confidence interval (CI), 1.3&ndash, 4.4). However, after analyzing the genetic profiles, in the absence of polymorphisms of all three analyzed genes, there was no association between a high frequency of meat consumption and the occurrence of CRC. In the case of GSTM1 gene polymorphism, the high frequency of meat consumption increased the risk of CRC by almost more than 4 times (OR adjusted for sex and age = 3.8, 95% CI: 1.6&ndash, 9.1). For GSTP1 gene polymorphism, a 3-fold increase in CRC risk was observed with a high frequency of meat consumption (OR adjusted for sex and age = 3.4, 95% CI: 1.4&ndash, 8.1). In the case of GSTT1 gene polymorphism, the increase in risk of CRC was not statistically significant (OR adjusted for sex and age = 1.9, 95% CI: 0.4&ndash, 8.5). Conclusions: The frequency of red meat intake in non-smokers increases the risk of colon cancer in the case of GST gene polymorphisms.

Background It is well known that hepatocellular carcinoma (HCC) has been one of the most life-threatening diseases all over the world. Plenty of internal and extrinsic factors have been proven to be related to HCC, such as gene mutation, viral hepatitis, and Nitrosamines. Though previous studies demonstrated that glutathione S-transferase (GST) genotypes are associated with HCC, the conclusions are inconsistent. Therefore, we carried on a renewed meta-analysis to expound the connection between the null GSTM1, GSTT1 polymorphisms and the risk of HCC. Methods We searched PubMed, Web of Science, Embase, and CNKI databases to select qualified researches which satisfied the inclusion criteria up to July 31, 2018. Finally, we selected 41 articles with 6124 cases and 9781 controls in this meta-analysis. We use ORs and 95% confidence interval (CI) to evaluate the correlation intension between the GSTM1 and GSTT1 null genes and the risk of HCC. All the statistical processes were executed by Stata (version 12.0). Results The pooled analysis showed that both GSTM1 null genotypes (OR = 1.37, 95% CI = 1.18–1.59) and GSTT1 null genotypes (OR = 1.43, 95% CI = 1.23–1.66) increased the risk of HCC. And GSTM1–GSTT1 dual-null genotypes also increased the risk of HCC (OR = 1.58, 95% CI = 1.22–2.05). In the subgroup analysis, we obtained significant results among Asians when stratified by race, and the results are GSTM1 null OR = 1.44, 95% CI = (1.22–1.71), GSTT1 null OR = 1.48, 95% CI = (1.25–1.77), GSTM1–GSTT1 null OR = 1.58, 95% CI = (1.19–2.09), while we didn’t obtain significant results among Caucasians or Africans. Stratified analyses on the type of control indicated a higher risk of HCC associated with GSTM1, GSTT1 single null genotypes and GSTM1–GSTT1 dual-null genotypes in healthy people. No evidence of significant connection was discovered in chronic liver disease (CLD) except in GSTT1 single null. Conclusions Our study indicated that an individual who carries the GSTM1, GSTT1 single null genotypes and GSTT1–GSTM1 dual-null genotypes is more likely to develop HCC. Electronic supplementary material The online version of this article (10.1186/s12935-019-0792-3) contains supplementary material, which is available to authorized users.

Thirty-five previous meta-analyses have been reported on the individual glutathione S-transferase M1 (GSTM1) present/null, glutathione S-transferase T1 (GSTT1) present/null, and glutathione S-transferase P1 (GSTP1) IIe105Val polymorphisms with lung cancer (LC) risk. However, they did not appraise the credibility and explore the combined effects between the 3 genes and LC risk. We performed a meta-analysis and re-analysis of systematic previous meta-analyses to solve the above problems. Meta-analyses of Observational Studies in Epidemiology guidelines were used. Moreover, we employed false-positive report probability (FPRP), Bayesian false discovery probability (BFDP), and the Venice criteria to verify the credibility of current and previous meta-analyses. Significantly increased LC risk was considered as “highly credible” or “positive” for GSTM1 null genotype in Japanese (odds ratio (OR) = 1.30, 95% confidence interval (CI) = 1.17–1.44, I2 = 0.0%, statistical power = 0.997, FPRP = 0.008, BFDP = 0.037, and Venice criteria: AAB), for GSTT1 null genotype in Asians (OR = 1.23, 95% CI = 1.12–1.36, I2 = 49.1%, statistical power = 1.000, FPRP = 0.051, BFDP = 0.771, and Venice criteria: ABB), especially Chinese populations (OR = 1.31, 95% CI = 1.16–1.49, I2 = 48.9%, Statistical power = 0.980, FPRP = 0.039, BFDP = 0.673, and Venice criteria: ABB), and for GSTP1 IIe105Val polymorphism in Asians (Val vs IIe: OR = 1.28, 95% CI = 1.17–1.42, I2 = 30.3%, statistical power = 0.999, FPRP = 0.003, BFDP = 0.183, and Venice criteria: ABB). Significantly increased lung adenocarcinoma (AC) risk was also considered as “highly credible” or “positive” in Asians for the GSTM1 (OR = 1.35, 95% CI = 1.22–1.48, I2 = 25.5%, statistical power = 0.988, FPRP

Introduction: Human exposure to parabens is very common in daily life, and prenatal exposure to these chemicals is associated with poor birth outcomes. Therefore, the aim of this study was to investigate the effect of glutathione S-transferase (GST) polymorphisms on the association between prenatal exposure to parabens and birth outcomes. Methods: We conducted a multivariate analysis involving 177 subjects to determine the association between paraben concentrations and birth outcomes in mothers with GST mu 1 (GSTM1) and GST theta 1 (GSTT1) polymorphisms from 2017 to 2019. Furthermore, we determined the interactive effect between paraben levels and GSTM1/GSTT1 polymorphisms using regression analysis, in addition to a generalized linear model after stratifying GSTM1/GSTT1 genotype into three categories. Results: Methyl and propyl paraben concentrations were significantly and positively associated with birth weight (methyl, β = 116.525, 95% confidence interval (CI) = 22.460–210.590, propyl, β = 82.352, 95% CI = 9.147–155.557) in individuals with the GSTM1-null genotype. Moreover, the propyl paraben concentration was significantly associated with an increase in gestational age (β = 0.312, 95% CI = 0.085–0.539) in individuals with the GSTM1-null genotype. Conclusions: This study reported the association between prenatal paraben exposure and birth outcomes in individuals with GST polymorphisms. We found positive relationships of maternal exposure to methyl parabens with birth weight in both mothers with GSTM1 and GSTT1-null genotypes.

Background: The published literature contains conflicting results regarding the impact of the glutathione S-transferase T1 (GSTT1) null genotype on the susceptibility to inflammatory bowel disease. Therefore, we conducted a meta-analysis of observational studies to assess the association. Methods: We searched four online databases for eligible studies. The odds ratio (OR) with 95% CI was used to assess the gene-disease association. We also performed subgroup analyses by type of inflammatory bowel disease and ethnicity. Results: There were 16 individual studies from 11 publications included in the analysis. There were 3366 cases with inflammatory bowel disease and 6013 controls. The meta-analysis of all 16 studies showed the GSTT1 null genotype was associated with increased susceptibility to inflammatory bowel disease (OR = 1.98, 95%CI 1.39-2.84, P < 0.001). The subgroup analysis by ethnicity further identified an association between the GSTT1 null genotype and inflammatory bowel disease in Caucasians, Asians, and Africans. The GSTT1 null genotype was associated with both ulcerative colitis (OR = 1.96, P = 0.004) and Crohn’s disease (OR = 2.01, P = 0.022). The GSTT1 null genotype was still significantly associated with ulcerative colitis (OR = 1.63, P < 0.0001) and Crohn’s disease (OR = 1.40, P = 0.023) after adjusting for study heterogeneity. Conclusion: The GSTT1 null genotype is significantly associated with an increased susceptibility to inflammatory bowel disease and is a risk factor for both ulcerative colitis and Crohn’s disease.

Hodgkin?s Lymphoma (HL) is a heterogeneous malignant disease of lymph node. The glutathione S-transferases (GSTs) have an important role in the detoxification of a wide variety of toxins and carcinogens. Studies have been indicated that genetic variation in the GST gene family may lead to susceptibility in HL. Hereby, we investigated the association of GSTT1 and GSTM1 null genotypes with HL in the Iranian population. This case-control study consisted of 76 patients suffering from HL and 120 healthy individuals as a control group. Genomic DNA was extracted and genotyping of GSTT1 and GSTM1 genes for the identification of their null genotypes was carried out using multiplex PCR method. Our findings indicated that GSTM1 null genotype is associated with risk of developing HL in our population (P=0.025; OR=2.00; 95%CI=1.110- 3.602); however, no association was found for GSTT1 null genotype. Our study also showed that the GSTM1 null genotype increased the risk of disease in the individuals younger than 45 years, and it had a positive association with low ESR. GSTM1 null genotype may have the key role in increasing the risk of HL in the Iranian population.

Background: Incidence of bladder cancer has increased rapidly worldwide in the past few years. Environmental as well as genetic factors are involved in the etiology of bladder cancer. Glutathione S transferase mu 1 (GSTM1) and glutathione S transferase theta 1 (GSTT1) genes are two xenobiotic metabolizing genes in phase II of detoxification process. Aim: The current study was aimed to find out the association of different environmental factors and GSTM1 and GSTT1 gene polymorphisms with susceptibility to bladder cancer in Pakistani population. Method: Bladder cancer cases (236) and control blood samples (270) were screened using phenol chloroform method of DNA extraction followed by multiplex PCR. Results: With respect to age; bladder cancer was more prevalent in age >60 years and low grade tumors were more frequent than high grade tumors. Smokers had a significantly higher incidence rate of cancer; also family history of cancer was found to be strongly associated ( P < 0.05) with bladder cancer. Commonly reported symptoms by the patients of bladder cancer were hematuria, lower urinary tract symptoms (LUTS) and flank pain. A larger number of patients had undergone surgery, chemotherapy and radiotherapy. Similarly GSTM1 (OR 2.24; CI 1.5–3.2; P = 0.0001) and GSTT1 (OR 2.9; CI 1.4–6.1; P = 0.002) gene deletion showed a highly significant association with bladder cancer. Simultaneous deletions of both GSTM1 and GSTT1 genes also showed highly significant association (OR 5.3; CI 2.1–13.1; P =0.0001) with cancer risk. No association was found when both of the two genes deletion was compared with bladder cancer among smokers. Conclusion: This study suggests that GSTM1 and GSTT1 gene polymorphisms may be associated with increased susceptibility toward bladder cancer in Pakistani population. Keywords: GSTM1; GSTT1; Bladder cancer; PCR; Polymorphism

// Cui Yu 1 , Chen Hequn 1 , Liu Longfei 1 , Wang Long 1 , Chen Zhi 1 , Zeng Feng 1 , Chen Jinbo 1 , Li Chao 1 , Zu Xiongbing 1 1 Department of Urology, Xiangya Hospital, Central South University, Changsha, Hunan 410000, China Correspondence to: Zu Xiongbing, email: zuxbxy@126.com Keywords: GSTM1, GSTT1, polymorphism, bladder cancer Received: September 06, 2016 Accepted: November 16, 2016 Published: November 29, 2016 ABSTRACT Background: Previous studies have indicated association between GSTM1 and GSTT1 gene polymorphisms and bladder cancer susceptibility, but the results have been inconclusive. Here, we performed a meta-analysis to investigate the association between GSTM1 / GSTT1 deletion polymorphisms and bladder cancer susceptibility. Methods: We searched for all studies investigating the association between GSTM1 or GSTT1 polymorphism and bladder cancer susceptibility in Pubmed, Web of Knowledge, and the Cochrane Central Search Library. A systematic review and meta-analysis were performed. Subgroup analyses were performed on different ethnicity, population-based and smoking status. Results: Our search identified 63 studies. GSTM1 null, GSTT1 null and GSTM1 / GSTT1 double-null genotypes were associated with increased risk of bladder cancer (OR: 1.36 95% CI: 1.25-1.47, P

Background: Endometriosis influenced by both genetic and environmental factors. Associations of glutathione S-transferases (GSTs) genes polymorphisms in endometriosis have been investigated by various researchers; however, the results are not consistent. Objective: We examined the associations of GSTM1 and GSTT1 null genotypes and GSTP1 313 A/G polymorphisms with endometriosis in an Iranian population. Materials and Methods: In this case-control study, 151 women with diagnosis of endometriosis and 156 normal healthy women as control group were included. The genotyping was determined using multiplex PCR and PCR- RFLP methods. Results: The GSTM1 null genotype was significantly higher (p=0.027) in the cases (7.3%) than the control group (1.3%). There was no significant difference between the frequency of GSTT1 genotypes between the cases and controls. The GSTP1 313 AG genotype was significantly lower (p=0.048) in the case (33.1%) than the control group (44.4%). Conclusion: Our results showed that GSTM1 and GSTP1 polymorphisms may be associated with susceptibility of endometriosis in Iranian women. Key

We observed inconsistent conclusions regarding the genetic role of glutathione S-transferase gene polymorphisms, including glutathione S-transferase M1 (GSTM1), glutathione S-transferase T1 (GSTT1) present/null, and glutathione S-transferase pi (GSTP1) Ile105Val polymorphisms, in the susceptibility to nasal or colorectal polyposis (NP or CP). Thus, we aimed to perform a meta-analysis to comprehensively evaluate this association by applying Stata/SE software. After the heterogeneity assumption, Mantel–Haenszel statistics were used to obtain the odds ratio (OR), 95% confidence interval (95% CI) and P-value of the association test (PA). We obtained a total of 235 articles by searching online databases. After screening, ten eligible case–control studies were finally enrolled in our meta-analysis. For the meta-analysis of the GSTT1 gene under present versus null, we observed a decreased risk of NP [OR = 0.65; PA=0.018], but not CP. In addition, we did not detect any evident association between the GSTM1 present/null polymorphism and NP or CP risk. For the meta-analysis of the GSTP1 Ile105Val polymorphism, compared with controls, an increased risk of NP cases was detected under the models of Val versus Ile (OR = 1.36; PA=0.027), Ile/Val versus Ile/Ile (OR = 1.70; PA=0.011) and Ile/Val+Val/Val versus Ile/Ile (OR = 1.65; PA=0.010). In conclusion, the null genotype of the GSTT1 polymorphism may be linked to an increased susceptibility to NP, whereas the Ile/Val genotype of the GSTP1 Ile105Val polymorphism may be associated with a decreased risk of NP.