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Disease manifestations or susceptibilities often differ among individuals exposed to the same concentrations of arsenic (As). These differences have been associated with several factors including As metabolism, sex, age, genetic variants, nutritional status, smoking, and others. This study evaluated the associations between four As metabolism-related gene polymorphisms/null genotypes with urinary As methylation profiles in girls and boys chronically exposed to As. In a total of 332 children aged 6-12 years, the frequency of AS3MT, GSTO1, GSTT1, and GSTM1 polymorphisms/null genotypes and As urinary metabolites were measured. The results revealed that total As and monomethyl metabolites of As (MMA) levels were higher in boys than in girls. No differences in the frequency of the evaluated polymorphisms were found between girls and boys. In AS3MT-Met287Thr carriers, %MMA levels were higher and second methylation levels (defined as dimethylarsinic acid divided by MMA) were lower. In children with the GSTM1 null genotype, second methylation levels were higher. In boys, a positive association between the AS3MT-Met287Thr polymorphism with %MMA and between the GSTO1-Glu155del and Asv was found; whereas, a negative relationship was identified between AS3MT-Met287Thr and second methylation profiles. In girls, a positive association was found between the GSTO1-Ala140Asp polymorphism with second methylation levels. In conclusion, our data indicate that gender, high As exposure levels, and polymorphisms in the evaluated genes negatively influenced As metabolism. Environ. Mol. Mutagen. 57:516-525, 2016. © 2016 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Attention deficit and hyperactivity disorder (ADHD) is highly heritable disorder and common in school-age children characterized by inattention, hyperactivity and impulsivity. Although its heritability was estimated at 80–90% from family, adoption and twin studies, the molecular etiology of this disorder has not elucidated. Meanwhile, an impaired balance of oxidant-antioxidant status and increased oxidative stress is observed in ADHD, and it may imply a possible relationship between oxidative stress and etiology of ADHD. Glutathione S-transferase (GST) is antioxidant enzymes that play a key role in the cellular detoxification. In the present study, we examined the association between the genetic polymorphisms of GSTM1 , GSTP1 and GSTT1 , and ADHD in Korean children. Case–control study was conducted with 243 ADHD children and 327 controls. There were no significant associations between the polymorphisms and the incidence of ADHD ( p > 0.05). However, significant associations were observed in the stratified analyses. The frequency of GSTP1 Ile/Ile genotype is reached to the significant level in the hyperactivity subtype (88.2%) compared to controls (64.8%) ( p = 0.035) and the frequency of GSTT1 -null genotype is significantly higher in the inattentive boys ( p = 0.005). Similarly, GSTT1 -null genotype showed significant associations in combined subtype ( p = 0.016) and hyperactivity subtype ( p = 0.036) of the ADHD girls. Thus our result imply that the polymorphisms in the GST genes may affect ADHD, however, replication study for larger sample set and functional studies are crucial to confirm these findings. [ABSTRACT FROM AUTHOR]

Background Isolated exposure to diesel exhaust (DE) or allergen can cause decrements in lung function that are impacted by the presence of genetic variants in the glutathione-S-transferase ( GST ) family but the effect of GST interactions with DE-allergen co-exposure on lung function is unknown. We aimed to assess the impact of DE and allergen co-exposure on lung function and the influence of GSTM1 or GSTT1 variation Methods We used a blinded crossover study design with 17 atopic subjects exposed to filtered air (FA; the control for DE) or DE for 2 h. One hour following each exposure to DE or FA, bronchoscopy was performed to deliver a diluent-controlled segmental allergen challenge (SAC). Methacholine challenge and forced expiratory volume in 1 s (FEV 1 ) was performed pre-exposure (baseline airway responsiveness) and 24 h post-exposure (effect of co-exposure). Additionally, FEV 1 was performed hourly after DE/FA exposure and protein carbonyl content was measured in plasma as an oxidative stress marker. Results Changes in FEV 1 from baseline were dependent on time following allergen exposure. DE, as opposed to FA, led to a significant change in FEV 1 at 2 h post-allergen exposure in GSTT1 variants only (24.5±19.6% reduction in GSTT1 null individuals vs. 9.2±7.3% reduction in GSTT1 present individuals). Moreover, plasma protein carbonyl level 4 h after co-exposure was higher in the individuals who have the GSTT1 null genotype. Conclusions This suggests a gene-environment interaction that endangers susceptible populations co-exposed to DE and allergen. [ABSTRACT FROM AUTHOR]

Background Exposure to disinfection by-products (DBPs) during pregnancy was associated with reduced foetal growth. Genetic susceptibility might play a role, especially for genes encoding for the Cytochrome P450 (CYP2E1) and Glutathione S-Transferase (GST) enzymes, involved in metabolism and activation of DBPs. Few epidemiological studies evaluated these gene-environment interactions and their results were never replicated. Objective This study aims to examine interactions between trihalomethanes (THM) or haloacetic acids (HAA) exposure and genetic polymorphisms on small for gestational age (SGA) neonates by investigating single nucleotide polymorphisms (SNPs) in CYP2E1 gene and GSTM1 and GSTT1 deletions in mothers-children pairs. Methods A population-based case-control study of 1549 mothers and 1455 children was conducted on SGA and THM/HAA exposure. DNA was extracted from blood or saliva cells. Targeted SNPs and deletions were genotyped. Statistical interaction between SNPs/deletions and THMs or HAAs in utero exposure with regard to SGA occurrence was evaluated by unconditional logistic regression with control of potential confounders. Results Previously reported positive modification of the effect of THM uterine exposure by mothers or newborns CYP2E1 rs3813867 C allele or GSTM1 deletion was not replicated. However interactions with CYP2E1 rs117618383 and rs2515641 were observed but were not statistically significant after correction for multiple testing. Conclusions Previous positive interactions between THMs exposure and CYP2E1 and GSTM1 were not replicated but interactions with other CYP2E1 polymorphisms are reported. [ABSTRACT FROM AUTHOR]

Background: Gastric and colorectal cancers remain the major causes of cancer-related death. Although chemotherapy improves the prognosis of the patients with gastrointestinal cancers, some patients do not benefit from therapy and are exposed to the adverse effects. The polymorphisms in genes including GSTM1 and GSTT1 have been explored to predict therapeutic efficacy; however, the results were inconsistent and inconclusive. Materials and methods: A systematic review and meta-analysis was performed by searching relevant studies about the association between the GSTM1 and GSTT1 polymorphisms and chemotherapy efficacy in gastrointestinal cancers in databases such as PubMed, EMBASE, Web of Science, Chinese National Knowledge Infrastructure, and Wanfang database up to January 10, 2016. Subgroup analyses were also performed according to ethnicity, cancer type, evaluation criteria, study type, chemotherapy type, and age. Results: A total of 19 articles containing 3,217 cases were finally included. Overall analysis suggested that no significance was found between overall toxicity, neurotoxicity, neutropenia, gastrointestinal toxicity, tumor response, and progression-free survival, and the polymorphisms in GSTM1 and GSTT1, while GSTM1 polymorphism associated with overall survival (OS; hazard ratio =1.213, 95% confidence interval =1.060-1.388, P=0.005). Subgroup analyses suggested that neurotoxicity was associated with GSTM1 polymorphism in the Asian population, neutropenia was associated with GSTM1 polymorphism in palliative chemotherapy and older patients (mean age >60 years), and tumor response was associated with GSTT1 polymorphism in gastric cancer and responders defined by complete and partial responses. Meanwhile, GSTM1 was associated with OS in Caucasians, Asians, those with colorectal cancer, and patients with mean age <60 years. GSTT1 polymorphism was also associated with OS in Caucasians and patients with mean age >60 years. Conclusion: The polymorphisms in GSTM1 and GSTT1 did not associate with the chemotherapy-related toxicity in gastrointestinal cancers, while GSTT1 polymorphism associated with OS, and further well-designed, larger-scale epidemiological studies are needed to validate our results. [ABSTRACT FROM AUTHOR]

Background: Several case-control studies investigating the relationship between genetic polymorphisms of glutathione S-transferase (GST) M1, GSTT1, and GSTP1 (rs1695) and the risk of breast cancer have reported contradictory results. We therefore performed a meta-analysis to clarify this issue.Materials and Methods: An updated meta-analysis using PubMed and Web of Knowledge databases for the eligible case-control studies was performed. Random- or fixed-effects model was used.Results: A total of 10,067 cancer cases and 12,276 controls in 41 independent case-control studies from 19 articles were included in this meta-analysis. Significant increase in risk of breast cancer for Asians was found in GSTM1-null genotype (P=0.012, odds ratio [OR] =1.17, 95% confidence interval [CI] =1.04-1.32) and GSTT1-null genotype (P=0.039, OR =1.19, 95% CI =1.01-1.41). In addition, our results showed that the GSTP1 (rs1695) polymorphisms can significantly increase the risk among Caucasians (P=0.042, OR =1.16, 95% CI =1.01-1.34). Sensitivity analysis and publication bias further confirmed the dependability of the results in this meta-analysis.Conclusion: Our results demonstrate that both GSTM1- and GSTT1-null polymorphisms are associated with an increased risk of breast cancer in Asians and that GSTP1 Val105Ile (rs1695) polymorphism is associated with an increased breast cancer risk in Caucasians. [ABSTRACT FROM AUTHOR]

Oxidative stress was related with carpal tunnel syndrome (CTS). We aimed to clarify the associations between glutathione S-transferase (GST)M1, GSTT1 and GSTP1-Ile105Val polymorphisms and CTS. One hundred-forty patients with CTS and 97 healthy controls were enrolled in this study. Tinel and Phalen signs were noted as positive or negative. Functional and clinical status of patients was evaluated by the Boston Questionnaire. The intensity of hand and/or wrist pain was evaluated on 10 cm visual analog scale (VAS). We applied the polymerase chain reaction (PCR) to determine the polymorphisms of the GSTM1 and GSTT1 and the PCR-restriction fragment length polymorphism method for detecting the GSTP1-Ile105Val polymorphism. The M1 null genotype was significantly higher in patients with CTS compared to healthy controls, and the M1 null genotype seemed to increase the risk of CTS approximately two-fold ( P = 0.011; odds ratio (OR) = 1.98; 95 % confidence interval (CI) 1.17-3.36). The M1 null, T1 present combined genotype was significantly higher in patients with CTS compared to healthy controls ( P = 0.043); however, it seemed not to increase the risk of CTS ( P = 0.14; OR = 0.62; 95 % CI 0.33-1.76). We found significantly higher levels of the VAS, Boston Symptom Severity Scale and Phalen sign in patients with the Ile/Val or the Val/Val genotypes compared to those in patients with the Ile/Ile genotype ( P = 0.003, 0.004 and 0.044, respectively). We proposed that genes involved in the protection from oxidative stress may influence the susceptibility, clinical and functional status of CTS. The GSTM1 null genotype may be related with the development of CTS, whereas the Val allele of GSTP1-Ile105Val polymorphism may be associated with worse functional and clinical status in CTS. [ABSTRACT FROM AUTHOR]

Trihalomethanes (THMs) have been reported to be associated with altered semen quality, and this association may be modified by inherited differences in cytochrome P450 (CYP2E1) and glutathione S-transferase (GSTZ1 and GSTT1), which metabolize THMs. We conducted a cross-sectional study to examine the interactions between CYP2E1, GSTZ1 and GSTT1 polymorphisms and exposure to THMs on semen quality among 401 men from the Reproductive Center of Tongji Hospital in Wuhan China. The baseline blood concentrations of four individual THMs, chloroform (TCM), bromodichloromethane (BDCM), dibromochloromethane (DBCM) and bromoform (TBM), were measured as biomarkers of exposure to drinking water THMs. Genotypes were determined by real-time PCR, and semen-quality parameters were evaluated according to the World Health Organization guidelines. GSTT1 genotype significantly modified the association between exposure to Br-THMs (sum of BDCM, DBCM and TBM) and below-reference sperm motility (Pint=0.02). Men with above-median blood Br-THM levels had an increased odds ratio (OR) of below-reference sperm compared to men with below-median blood Br-THM levels (OR=2.15, 95% CI: 1.11, 4.19) in the GSTT1 null genotype only. In addition, we found that men with a TT of CYP2E1 rs 915,906 had higher blood TCM and TTHM (sum of TCM, BDCM, DBCM and TBM) concentrations than men with a CT/CC of CYP2E1 rs 915,906. Our results suggest that GSTT1 polymorphisms modify Br-THM exposure relation with semen quality, and CYP2E1 polymorphisms are associated with internal levels of exposure to THMs. [ABSTRACT FROM AUTHOR]

In this study, we aimed at investigating the association between glutathione- S-transferase (GSTM1 and GSTT1) deletion genotypes and susceptibility to non-arteritic anterior ischemic optic neuropathy (NAION). We hope our findings may contribute to the understanding NAION pathogenesis and provide some clues for the prevention and treatment of optic diseases. The NAION group contains 113 subjects (33 males and 80 females, mean age 55.3 ± 9.8). And 98 subjects were enrolled in the control group (32 males and 66 females, mean age 56.7 ± 10.2). The individuals involved in the study were matched by gender and age to obtain two homogenous groups. GSTM1− and GSTT1− genotype and the combined genotype were investigated. The genotype distributions in NAION patients were compared with those in the controls. Significantly altered intraocular pressure (IOP) and cup-to-disc ratio (CDR) was detected between NAION patients and controls. An increased risk of NAION was observed among individuals with GSTM1− ( P < 0.001). No significant difference was confirmed for GSTT1− ( P = 0.290). Individuals with GSTM1−/GSTT1− have a higher susceptibility to NAION ( P < 0.001); the GSTM1−/GSTT1+ genotype also had a significantly higher frequency in patients than in controls ( P = 0.004). But the genotype of GSTM1+/GSTT1− seems to have no connection with NAION ( P = 0.476). In conclusion, in this study, we confirmed the connection between NAION and GSTM1− genotype. But no significant association was observed between GSTT1− genotype and NAION susceptibility. In further analysis regarding combined genotype, a trend of protective effect was detected for GSTT1+ genotype. It is indicated by our result that oxidative compounds might play an important part in the pathogenesis of NAION. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Aim: Lung cancer has increased rapidly in the past few decades. Environmental and genetic factors are contributing toward its incidence. Several studies have been reported with conflicting results regarding polymorphism of GSTM1 and GSTT1 genes and their contribution in development of lung cancer. It has been observed that these genetic polymorphisms show geographical variations. Therefore, we conducted a case control study to find the association of various environmental factors as well as GSTM1 and GSTT1 deletion with susceptibility of lung cancer.Patients and Methods: DNA of pathologically confirmed lung cancer patients and cancer-free controls were amplified using multiplex PCR to check the deletion of GSTM1 and GSTT1 genes.Results: Demographic factors like age, gender, smoking, passive smoking, smoking duration, smoking dose and other addictions were found to be significantly related (P = 0.05) with incidence of lung cancer. Deletion of GSTM1 and GSTT1 showed non--significant results (P = 0.05) when comparing with development of lung cancer.Conclusion: Results revealed that certain environmental factors may be considered as a risk factor but deletion of GSTM1 and GSTT1 are not associated with the development of lung cancer; however, studies including >500 patient samples is suggested. [ABSTRACT FROM AUTHOR]

The genes glutathione S-transferase M1 (GSTM1) and GSTT1 code for cytosolic enzymes GSTµ and GSTθ, respectively, which are involved in phase II metabolism. In human, both genes may be deleted. In the present study, the genetic polymorphisms of GSTM1 and GSTT1 were detected by PCR method in 236 healthy individuals from Shiraz population, Fars province, south of Iran. The frequency of GSTM1 and GSTT1-null genotypes were 37.7 and 31.8 percent, respectively. The studied population was then compared with reported frequencies for neighboring populations, as well as, with those for European and African populations.

Background and Aim: Different studies have shown pharmacogenetic variants related to drug toxicity in acute myeloid leukemia (AML) patients. Our aim was to identify the association between ABCB1, CDA, DCK, GSTT1, and GSTM1 variants with clinical outcomes and toxicity in pediatric patients with AML., Methods: Fifty-one confirmed de novo AML pediatric patients were included. A SNaPshot™ assay and conventional PCR were used to evaluate ABCB1, CDA, DCK, GSTT1, and GSTM1 variants. Clinical outcomes and toxicity associations were evaluated using odds ratios and Chi-square analysis., Results: Patients carrying ABCB1 (1236C > T, rs1128503) GG genotype in had a 6.8 OR (CI 95% 1.08-42.73, p = .044) for cardiotoxicity as compared to patients carrying either AA or GA genotypes 0.14 OR (CI 95% 0.023-0.92, p = .044). For ABCB1 (1236G > A rs1128503/2677C > A/T rs2032582/3435G > A rs1045642) AA/AA/AA combined genotypes had a strong association with death after HSTC OR 13.73 (CI 95% 1.94-97.17, p = .009). Combined genotypes GG/CC/GG with CDA (79A > C, rs2072671) CA genotype or CDA (-451G > A, rs532545) CT genotype, had a 4.11 OR (CI 95% 2.32-725, p = .007) and 3.8 OR (CI 95% 2.23-6.47, p = .027) with MRD >0.1% after first chemotherapy cycle, respectively., Conclusion: Our results highlight the importance of pharmacogenetic analysis in pediatric AML, particularly in populations with a high degree of admixture, and might be useful as a future tool for patient stratification for treatment., (© 2022 The Authors. Cancer Reports published by Wiley Periodicals LLC.)

Prostate cancer (PCa) is the most commonly diagnosed cancer in the developed world, and the incidence of this cancer is rising rapidly in many countries. Several polymorphic genes encoding enzymes involved carcinogenesis have been studied as potential risk factor of prostate cancer. Genetic polymorphisms in glutathione S-transferases M1 ( GSTM1), T1 ( GSTT1) and P1 ( GSTP1) genes have been constantly reported to have a meaningful effect on prostate cancer risk. But other surveys of this relationship have yielded inconsistent results. To assess the possible contribution of the GSTM1, GSTT1, and GSTP1 gene polymorphisms in prostate cancer, we performed a population-based study of 139 prostate cancer patients and 115 healthy controls based on their genotype distributions of the genes. There were no differences in distributions of genotype frequencies of GSTM1 and GSTP1 polymorphisms between prostate cancer patients and controls (OR 1.60, 95 % CI 0.886-2.860 for GSTM1 and OR 1.38, 95 % CI 0.739-2.577 for GSTP1). In contrast, the distribution of GSTT1-null genotype is significantly different between the prostate cancer case and controls (OR 0.26, 95 % CI 0.128-0.518, p < 0.001). Meanwhile, GSTP1 I/V and V/V genotypes were significantly associated with prostate cancer where the PSA level was more than 10.0 (OR 2.73, 95 % CI 1.319-5.639, p = 0.006). Thus, our data imply that the GSTT1-null genotype may not be a risk factor but a protective factor of prostate cancer and GSTP1 Val allele is a risk factor for the prostate cancer where the PSA level was high, although functional studies with larger sample size are necessary to elucidate these findings. [ABSTRACT FROM AUTHOR]

Ankylosing spondylitis (AS) is a chronic inflammatory disease of unknown origin. The aim of this study is to clarify the relationships between susceptibility and severity of AS and GST- mu1 ( GSTM1), GST- theta1 ( GSTT1), GST- pi1 ( GSTP1)- Ile105Val and angiotensin- converting enzyme ( ACE) I/D polymorphisms in AS patients. One hundred thirty-eight AS patients and seventy-one healthy controls were enrolled in this study. Erythrocyte sedimentation rate and C-reactive protein (CRP) levels of the AS patients were recorded. The scores of the numeric rating scale (NRS) pain, the Bath Ankylosing Spondylitis Activity Index, the Bath Ankylosing Spondylitis Metrology Index and the Bath Ankylosing Spondylitis Functional Index were calculated. The genotypes distributions and allele frequencies of GSTM1, GSTT1, GSTP1- Ile105Val and ACE I/D polymorphisms were compared between patients and healthy controls. The Multiplex polymerase chain reaction (PCR) and the PCR-restriction fragment length polymorphism methods were used to detect the polymorphisms of ACE I/D, the GSTT1 and GSTM1 genes and the GSTP1- Ile105Val polymorphism, respectively. There were significantly higher levels of the GSTT1 null and the ACE II genotypes in AS patients compared to those in healthy controls ( p = 0.002 and 0.005, respectively). We found significantly higher levels of CRP and the NRS pain scores in the patients with ACE ID or DD genotypes compared to those in the patients with ACE II genotypes ( p = 0.005 and 0.035, respectively). The present results showed that genes involved in protection from oxidative stress and ACE gene may influence disease development and course in AS. [ABSTRACT FROM AUTHOR]

Observational studies have reported controversial results on the association between GSTT1 and GSTM1 genotypes and treatment outcome of breast cancer. The purpose of this study is to evaluate the association between GSTT1 and GSTM1 and treatment outcome in breast cancer patients. Eligible studies were searched in PubMed, EMBASE, Cochrane Library, and China National Knowledge Infrastructure databases. A random-effect model or fixed-effect model was used to calculate the overall combined risk estimates. Twenty-one studies with a total of 4990 patients were included in this meta-analysis. The GSTM1 null genotype (odds ratio (OR) = 1.33, 95 % confidence interval (CI) 1.01-1.75, P = 0.046) and GSTT1/ GSTM1 double null genotype (OR = 2.22, 95 % CI 1.02-4.84, P = 0.045) were significantly associated with an increased tumor response. A reduced overall survival (hazard ratio (HR) = 0.84, 95 % CI 0.72-0.98, P = 0.024) was observed in GSTM1 null genotype, especially in mixed descent (HR = 0.77, 95 % CI 0.61-0.96, P = 0.018) and large sample size (HR = 0.85, 95 % CI 0.72-0.99, P = 0.033). Evidence of publication bias was observed in GSTM1 genotype rather than in GSTT1 genotype. This meta-analysis suggests that GSTM1 null and GSTT1/ GSTM1 double null polymorphisms might be significantly associated with an increased tumor response. However, the GSTM1 null genotype might be significantly associated with a reduced overall survival. Future studies are warranted to confirm these findings. [ABSTRACT FROM AUTHOR]

Benzene is a known human carcinogen which must be activated to benzene oxide (BO) to exert its carcinogenic potential. BO can be detoxified in vivo by reaction with glutathione and excretion in the urine as S -phenylmercapturic acid. This process may be catalyzed by glutathione S -transferases (GSTs), but kinetic data for this reaction have not been published. Therefore, we incubated GSTA1, GSTT1, GSTM1, and GSTP1 with glutathione and BO and quantified the formation of S -phenylglutathione. Kinetic parameters were determined for GSTT1 and GSTP1. At 37 °C, the putative K m and V max values for GSTT1 were 420 μM and 450 fmol/s, respectively, while those for GSTP1 were 3600 μM and 3100 fmol/s. GSTA1 and GSTM1 did not exhibit sufficient activity for determination of kinetic parameters. We conclude that GSTT1 is a critical enzyme in the detoxification of BO and that GSTP1 may also play an important role, while GSTA1 and GSTM1 seem to be less important. [ABSTRACT FROM AUTHOR]

In view of the controversies surrounding the glutathione-S-transferases (GST) M1/T1–endometriosis association, a meta-analysis of the GSTM1/GSTT1 genetic association studies of endometriosis was performed in Chinese populations. PubMed, Springer Link, OvidSP, and Chinese databases were searched for related studies. A total of nine studies on GSTM1-endometriosis involved 874 cases and 997 controls, and five studies on GSTT1 involved 404 cases and 513 controls were included in this meta-analysis. Overall, the null genotype of GSTM1/GSTT1 was significantly related to endometriosis risk in Chinese populations (GSTM1, OR = 2.21, 95% CI: 1.22–4.01; GSTT1, OR = 2.31, 95% CI: 1.34–3.99). In subgroup analyses stratified by ethnicity and source of controls, the same results were observed in Chinese Han and population-based studies. The sensitivity analysis confirmed the reliability and stability of the meta-analysis. No publication bias was found among studies by Egger’s test. In conclusion, our meta-analysis supports that the GSTM1/GSTT1 null genotype might contribute to individual susceptibility to endometriosis in Chinese populations, especially in Chinese Han. 鉴于围绕谷胱甘肽巯基转移酶（GST）M1/T1与子宫内膜异位症的关联的争议，对此在中国人群中进行一项有关GSTM1/GSTT1和子宫内膜异位症遗传关系的荟萃分析。在PubMed, Springer Link, OvidSP以及中国数据库中搜索了相关的研究。这项荟萃分析共有9项有关GSTM1和子宫内膜异位症的研究，包括874例病例和997例对照，5项有关GSTT1的研究，包括404例病例及513例对照。整体来说，在中国人群中，GSTM1/GSTT1基因型缺失和患子宫内膜异位症风险是显著相关的(GSTM1,OR=2.21, 95% CI：1.22–4.01； GSTT1， OR=2.31，95% CI：1.34–3.99)。在亚组分析中，按照种族和控制源分组，在汉族和基于人口的研究中可以得到相同的结果。敏感性分析证实了荟萃分析的可靠性和稳定性。使用艾格测试，在所有的研究中，没有发现发表偏倚。总之，我们的荟萃分析支持：GSTM1/GSTT1基因型缺失可能提高中国人群对子宫内膜异位症的易感性，尤其是汉族人群。 [ABSTRACT FROM PUBLISHER]

This study investigated genetic damage in gasoline pump workers using the cytokinesis blocked micronucleus (CBMN) assay. Blood and urine samples were collected from 50 gasoline pump workers and 50 control participants matched with respect to age and other confounding factors except for exposure to benzene through gasoline vapors. To determine the benzene exposure, phenol was analyzed in urinary samples of exposed and control participants. Urinary mean phenol level was found to be significantly high (P < 0.05) in exposed workers. The CBMN frequency was found to be significantly higher in gasoline pump workers (6.70 ± 1.78) when compared to control individuals (2.20 ± 0.63; P < 0.05). We also investigated influence of polymorphisms of GSTM1, GSTT1, and GSTP1 genes on CBMN frequency. The individuals having GSTM1 and GSTT1 null genotypes had significantly higher frequency of CBMN (P < 0.05). Our study indicates that chronic and long-term exposure of gasoline vapors can increase genotoxic risk in gasoline pump workers. [ABSTRACT FROM AUTHOR]

Glutathione S-transferase (GST) was suggested as an important contributor to Alzheimer's disease (AD). The GSTs polymorphisms have been investigated as candidate genetic risk factors for AD, yet results remained uncertain. Therefore, we performed a meta-analysis to clarify the relationship of GSTs polymorphisms with the occurrence of AD. PubMed, Embase, Cochrane library and Alzgene databases were searched and potential literatures were selected. Pooled analyses and subgroup analyses were conducted, and also publication bias tests and cumulative meta-analysis. This meta-analysis suggested null associations between polymorphisms of GSTM1, GSTT1, GSTM3, GSTP1, GSTO1 and AD risk. GSTs variants may not have an impact on the morbidity of Alzheimer's disease. Further well designed researches are required to confirm these findings of the current study. [ABSTRACT FROM AUTHOR]

Objective: Previous studies investigating the relationship between glutathione S-transferase T1 (GSTT1) gene deletion polymorphism and lung cancer risk among Chinese population produced inconsistent results. To obtain a precise conclusion, we performed this meta-analysis to evaluate the association between GSTT1 deletion polymorphism and lung cancer risk among Chinese population. Methods: The databases of Medline/PubMed, Embase, Web of Science, Wanfang Med Online, and Chinese National Knowledge Infrastructure were searched. The strength of the association was assessed by odds ratio (OR) with 95% confidence intervals (95% CI). Results: Overall, we found an increased lung cancer risk among subjects carrying GSTT1 null genotype compared with those carrying present genotype (OR =1.31, 95% CI: 1.12-1.52) on the basis of 20 studies with 3,351 cases and 4,683 controls. We also observed an increased risk of lung cancer among subjects carrying GSTT1 null genotype compared with those carrying present genotype in stratified analyses (OR =1.31, 95% CI: 1.11-1.55 for healthy subjects-based control; OR =2.29, 95% CI: 1.84-2.85 for squamous cell carcinoma and OR =1.47, 95% CI: 1.22-1.77 for adenocarcinoma, respectively). Conclusion: This meta-analysis suggested that GSTT1 deletion polymorphism might contribute to lung cancer risk among Chinese population. [ABSTRACT FROM AUTHOR]

BACKGROUND: GSTM1 and GSTT1 are phase II enzymes which provide chemical defense to cells. OBJECTIVE: This study was designed to evaluate association of GSTM1 and GSTT1 deletion along with epidemiological factors with risk of colon and rectum cancers. METHODOLOGY: Multiplex PCR was used for cancer patients as well as age and gender matched cancer free controls. RESULTS: Mean age of patients and controls was 45.5 (± 14.6) and 43.5 (± 18.08) years respectively. Among epidemiological factors; gender, age ≥ 50 years, active/passive smoking, naswar addiction, residential area, family history, red meat, fruit and vegetable intake showed no association with CRC (P ≥ 0.05). Symptoms of CRC like altered bowel habits (70%) was more common compared with other symptoms. GSTM1 (P ≤ 0.05) and GSTT1 (P ≤ 0.05) deletions were found to be significantly associated with CRC compared with controls. Association of epidemiological factors like gender, active/passive smoking, naswar addiction, residential area and family history were associated neither with GSTM1 deletion nor to GSTT1 deletion in both cancers (P ≤ 0.05). Significant association was present between stage III and GSTM1 (CI 95% 0.15-1.39) as well as GSTT1 (CI 95% 0.14-2.44) deletion in CRC. CONCLUSION: These results suggest that GSTM1 and GSTT1 deletion were associated with increased risk of colon and rectum cancer in Pakistani population. [ABSTRACT FROM AUTHOR]

Genetic polymorphisms in tobacco-metabolizing genes may modulate the risk of head and neck cancer (HNC). In Northeast India, head and neck cancers and tobacco consumption remains most prevalent. The aim of the study was to investigate the combined effect of cytochrome P450 1A1 ( CYP1A1) T3801C, glutathione S-transferases ( GSTs) genes polymorphisms and smoking and tobacco-betel quid chewing in the risk of HNC. The study included 420 subjects (180 cases and 240 controls) from Northeast Indian population. Polymorphisms of CYP1A1 T3801C and GST ( M1 & T1) were studied by polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) and multiplex PCR, respectively. Logistic regression (LR) and multifactor dimensionality reduction (MDR) approach were applied for statistical analysis. LR analysis revealed that subjects carrying CYP1A1 TC/CC + GSTM1 null genotypes had 3.52-fold ( P < 0.001) increase the risk of head and neck squamous cell carcinoma (HNSCC). Smokers carrying CYP1A1 TC/CC + GSTM1 null and CYP1A1 TC/CC + GSTT1 null genotypes showed significant association with HNC risk (odds ratio [OR] = 6.42; P < 0.001 and 3.86; P = 0.005, respectively). Similarly, tobacco-betel quid chewers carrying CYP1A1 TC/CC + GSTM1 null genotypes also had several fold increased risk of HNC ( P < 0.001). In MDR analysis, the best model for HNSCC risk was the four-factor model of tobacco-betel quid chewing, smoking, CYP1A1 TC/CC, and GSTM1 null genotypes (testing balance accuracy [TBA] = 0.6292; cross-validation consistency [CVC] = 9/10 and P < 0.0001). These findings suggest that interaction of combined genotypes of carcinogen-metabolizing genes with environmental factors might modulate susceptibility of HNC in Northeast Indian population. [ABSTRACT FROM AUTHOR]

Gene deletions in GSTM1 and GSTT1 may result in tempering the activation and detoxification of several carcinogens and thereby may increase the risk of cancer pre-disposition. This study aims to investigate the clinical impact of glutathione-S-transferase GSTM1 and GSTT1 polymorphisms on squamous cell carcinoma of cervix (SCCA).The GSTM1 and GSTT1 polymorphisms were analyzed in cervical cancer patients and healthy controls. Touch down multiplex polymerase chain reaction (PCR) strategy was adopted for genotyping of GSTM1 and GSTT1 polymorphisms. The null genotype of GSTM1 exhibited a significantly higher percentage in patients with SCCA (74 %) than in the control group (34.0 %). However, no significant difference was observed in the null genotype of GSTT1 among SCC patients and healthy subjects, respectively. GSTM1 exhibited a significant association with increased risk of squamous cell carcinoma ( p < 0.001). The odds ratio for the GSTM1 null genotype was also calculated (odds ratio 3.7484; 95 % confidence interval 1.6562-84834). This suggests that GSTM1 null genotype in cervical cell samples may be associated with more severe precancerous lesions of the cervix. [ABSTRACT FROM AUTHOR]

Objective: An association between endometriosis and the glutathione S-transferase M1 (GSTM1)- and GSTT1-related genes has been proposed on account of the detoxification properties of the GST enzymes. The aim of the present study was to investigate whether the polymorphisms and null mutations are associated with the susceptibility to endometriosis. Methods: The study included 105 women with endometriosis and 150 healthy women with no laparoscopic evidence of disease. Genotyping of the GSTM1 and GSTT1 gene polymorphisms was performed by Multiplex-PCR. Results: There was a significant association of GSTM1 null and GSTT1 null genotypes with endometriosis both when studied alone ( P = 0.001 and P = 0.03, respectively) and in combination ( P = 0.00002). Conclusion: The findings suggest that the GSTM1 and GSTT1 gene deficiency predisposes to endometriosis in a Tunisian population and can confer a significant increased risk when the GST null genotypes are combined. [ABSTRACT FROM AUTHOR]

ABSTRACT Occupational exposure to anaesthetic gases is one of the major hazards to healthcare personnel. We evaluated the cytogenetic effects of chronic exposure to low concentrations of anaesthetic gases in operating theatres. The study included 21 anesthetists and 21 control subjects who matched in age and gender. Chromosome aberrations (CAs) and sister chromatid exchanges (SCEs) assays were performed. All subjects were also genotyped for glutathione S-transferase T1 ( GSTT1) gene polymorphisms. Significant differences were found between exposed and controls in terms of SCEs frequency ( P = 0.001) and replication index value ( P = 0.005), but not in terms of CAs ( P = 0.201) and aberrant cells ( P = 0.227) frequencies. Regression analyses indicated that age and the years of employment did not influence the level of chromosomal damage in both groups. Finally, among anesthetists, GSTT1 null individuals showed a significant higher frequency of SCE with respect to GSTT1-positive subjects. [ABSTRACT FROM AUTHOR]

Background. Due to new genetic insights, a considerably large number of genes and polymorphic gene variants are screened and linked with the complex pathogenesis of type 2 diabetes (DM). Our study aimed to investigate the association between the two isoforms of the glutathione S-transferase genes (Glutathione S transferase isoemzyme type M1- GSTM1 and Glutathione S transferase isoemzyme type T1-GSTT1) and the prevalence of DM in the Northern Romanian population. Methods. We conducted a cross-sectional, randomized, case-control study evaluating the frequency of GSTM1 and GSTT1 null alleles in patients diagnosed with DM. A total of 106 patients diagnosed with DM and 124 healthy controls were included in the study. GSTM1 and GSTT1 null alleles genotyping was carried out using Multiplex PCR amplification of relevant gene fragments, followed by gel electrophoresis analysis of the resulting amplicons. Results. Molecular analysis did not reveal an increased frequency of the null GSTM1 and GSTT1 alleles (mutant genotypes) respectively in the DM group compared to controls (p=0.171, OR=1.444 CI=0.852-2.447; p=0.647, OR=0.854, CI=0.436-1.673). Nevertheless, the combined GSTM1/GSTT1 null genotypes were statistically significantly higher in DM patients compared to control subjects (p=0.0021, OR=0.313, CI=0.149-0.655) Conclusions. The main finding of our study is that the combined, double GSTM1/GSTT1 null genotypes are to be considered among the polymorphic genetic risk factors for type 2 DM. [ABSTRACT FROM AUTHOR]

Allele sharing between modern and archaic hominin genomes has been variously interpreted to have originated from ancestral genetic structure or through non-African introgression from archaic hominins. However, evolution of polymorphic human deletions that are shared with archaic hominin genomes has yet to be studied. We identified 427 polymorphic human deletions that are shared with archaic hominin genomes, approximately 87% of which originated before the Human-Neandertal divergence (ancient) and only approximately 9% of which have been introgressed from Neandertals (introgressed). Recurrence, incomplete lineage sorting between human and chimp lineages, and hominidspecific insertions constitute the remaining approximately 4% of allele sharing between humans and archaic hominins. We observed that ancient deletions correspond to more than 13% of all common (45% allele frequency) deletion variation among modern humans. Our analyses indicate that the genomic landscapes of both ancient and introgressed deletion variants were primarily shaped by purifying selection, eliminating large and exonic variants. We found 17 exonic deletions that are shared with archaic hominin genomes, including those leading to three fusion transcripts. The affected genes are involved in metabolism of external and internal compounds, growth and sperm formation, as well as susceptibility to psoriasis and Crohn's disease. Our analyses suggest that these "exonic" deletion variants have evolved through different adaptive forces, including balancing and population-specific positive selection. Our findings reveal that genomic structural variants that are shared between humans and archaic hominin genomes are common among modern humans and can influence biomedically and evolutionarily important phenotypes. [ABSTRACT FROM AUTHOR]

Exposure to benzene has been associated with haematological diseases such as neutropenia (NEB) and acute myeloid leukaemia (AML). We tested whether the null genotypes of the GSTM1 and GSTT1 genes, involved in benzene inactivation, altered the risk for NEB in southeastern Brazil. Genomic DNA from 55 NEB patients and 330 controls was analysed by multiplex-polymerase chain reaction. The frequency of the GSTM1, GSTT1 and combined null genotypes was similar in patients and controls (GSTM1, 27.3% vs. 38.8%, p = 0.16; GSTT1, 25.5% vs. 19.7%, p = 0.24; GSTM1/GSTT1, 12.7% vs. 6.7%, p = 0.26; respectively). The distribution of genotype classes in NEB patients was similar to normal controls, suggesting that GSTM1 and GSTT1 null genotypes make no specific contribution to the risk of NEB. As the GSTM1 and GSTT1 null genotypes were previously associated with increased risk for AML in Brazil and elsewhere, we hypothesise that different thresholds of chemical exposure relative to distinct GSTM1 and GSTT1 genotypes may determine whether AML or NEB manifests in benzene exposed individuals from southeastern Brazil. Although indicative, our results still require support by prospective and large scale epidemiological studies, with rigorous assessment of daily chemical exposures and control of the possible contribution of other polymorphic genes involved in benzene metabolism.

The null genotype for glutathione S-transferase (GST, EC 2.5.1.18) gene polymorphisms is considered a risk factor for leukemia in different populations. In this work we investigated the GSTT1 and GSTM1 polymorphisms using multiplex PCR in 53 patients with chronic myeloid leukemia (CML), 23 with acute promyelocytic leukemia (APL) and 304 apparently healthy controls. In this association study we found that the GSTT1null genotype was more frequent in our group of APL patients than in the control group [OR = 2.75 (95% CI = 1.10-6.88)], providing evidence that a deletion in the GSTT1 gene could be a risk factor for this type of leukemia.

The associations of organochlorine pesticides (OCPs) with semen quality from human studies are conflicting, and also it is largely unknown whether the associations are modified by genetic polymorphisms. We aimed to evaluate the associations between serum concentrations of 18 OCPs and semen quality among 387 Chinese men, and further to examine the modifying effects by genetic polymorphisms in cytochrome P450 (CYP2E1) and glutathione S-transferase (GSTT1). Multivariable linear regressions were used to evaluate the relationships between serum OCP concentrations and semen quality, and the role of CYP2E1 and GSTT1 polymorphisms in modifying the associations were assessed. Multiple testing was adjusted using the false discovery rate (FDR). We observed that men with detectable concentrations of serum ɤ-HCH had a decrease in sperm motility of 7.07% (95% CI: -10.9%, −3.24%) compared to those with undetectable concentrations (FDR- P value = 0.02). Men with TT of CYP2E1 rs 915906 genotypes had higher median concentrations of serum dieldrin compared with those with CT/CC of CYP2E1 rs 915906 genotypes. There were interactions between CYP2E1 and GSTT1 polymorphisms and certain OCPs namely ɤ-HCH, δ-HCH, dieldrin, endosulfan I, and endrin aldehyde on semen quality. For example, elevated dieldrin levels in relation to decreased sperm concentration, sperm count, and sperm motility were only observed among men with CC of CYP2E1 rs2031920 genotypes (all P interaction < 0.05). However, these interactions were not statistically significant after the FDR adjustment. Our results suggested that CYP2E1 and GSTT1 polymorphisms may modify the effects of OCP exposures on semen quality. Due to the relatively small size samples, further investigation is warranted to confirm the findings. [Display omitted] • Serum ɤ-HCH was associated with decreased sperm motility. • CYP2E1 rs915906 was associated with differences in serum dieldrin concentrations. • CYP2E1 polymorphisms modified the effects of certain OCP exposures on semen quality. • GSTT1 polymorphisms modified the effects of endrin aldehyde and sperm concentration. [ABSTRACT FROM AUTHOR]

Preterm delivery (PTD) is an adverse birth outcome associated with increased infant mortality and negative lifelong health consequences. PTD may be the result of interactions between genetics and maternal/fetal environmental factors including smoking exposure (SMK). A common deletion in the GSTT1 gene was previously reported to affect birth outcomes in smokers. In this study, we dissect the associations among SMK, birth outcomes, and copy number variations (CNVs) in the GSTT1/GSTT2 region.A preterm birth case-control dataset of 1937 mothers was part of the GENEVA preterm birth study, which included genome-wide genotyping used to identify CNVs. We examined the association of SMK with birth outcomes, detected CNVs within the GSTT1/GSTT2 region using PennCNV, and examined associations of the identified CNVs with preterm birth and with birth weight (BW) in full term birth controls, including interactions with SMK. Finally, we tested the association of CNVs in GSTT1/GSTT2 with SMK.We confirmed the association of smoking with low BW and PTD. We identified 2 CNVs in GSTT2 (GSTT2a and GSTT2b), 1 CNV in GSTTP1 and 2 CNVs in GSTT1 (GSTT1a and GSTT1b). The GSTT2a deletion was associated with reduced BW (-284g, p=2.5E-7) in smokers, and was more common in smokers (odds ratio[OR]=1.3, p=0.036). We found that the size of the reported common deletion CNV in GSTT1 was larger than previously shown. The GSTTP1 and GSTT1b null genotypes were in high linkage disequilibrium (LD) (D’=0.89) and less common in smokers (OR=0.68, p=0.019 and OR=0.73, p=0.055 respectively). These two deletions were in partial LD with GSTT2a and GSTT2b duplications. All 5 CNVs seem to be associated with increased risk of preterm birth before 35 completed weeks.CNVs in the GSTTT1/GSTT2 region appear associated with low BW and PTD outcomes, but LD complicated these CNVs in GSTT1/GSTT2. In genetic association studies of BW, multiple CNVs in this region need to be investigated instead of a single polymorphism.

Polymorphisms of xenobiotic detoxification genes GSTT1 and GSTM1 and activity of glutathione system enzymes were studied in men with infertility. The frequency of deletion variant of GSTT1 gene in men with infertility was by 2 times higher than in fertile men. Deletion variant of GSTM1 gene was 1.4-fold more frequent in infertile men than in fertile men. Complete deletion of two genes was found in 19% men with infertility and only in 6% fertile men. The balance of activity of glutathione system enzymes essential for the effective detoxification of exogenous xenobiotics and toxic endogenous metabolites was impaired in infertile carriers of deletion variants of genes. Our results suggest that adaptation mechanisms are disordered in infertile men. [ABSTRACT FROM AUTHOR]

Comparative analysis of the parameters of LPO, antioxidant defense (AOD), and the thiol/disulfide system was performed in fertile and infertile males of reproductive age carrying different genotypes of the glutathione system genes. Blood plasma, blood hemolysate, and ejaculate served as specimens for biochemical studies. A decrease in glutathione S-transferase activity was found in blood and ejaculate specimens from fertile and infertile carriers of nonfunctional GSTT1(0/0)/GSTM1(0/0) genotypes. In infertile carriers of nonfunctional GSTT1(0/0)/GSTM1(0/0) genotypes determining reduced glutathione S-transferase activity, a decrease in the concentration of low-molecular-weight cell antioxidant (reduced glutathione) and an increase in the concentration of secondary LPO products (TBA-reactive substances) were revealed. Identification of carriers the polymorphic GSTT1 and GSTM1 variants and analysis of activity of the thiol/disulfide system enzymes can be recommended for additional evaluation of the risk for reproductive dysfunction in men. [ABSTRACT FROM AUTHOR]

Objective: Chronic periodontal disease (CP) is a multifactorial infectious and inflammatory disease that occurs due to the challenge between the immune response of the host and specific periodontal bacteria, and that can lead to tooth loss due to damage inflicted to the supporting tissue. The current study investigates the genotypes of the GSTM1 and GSTT1 genes, along with the allelic frequency of the single nucleotide polymorphism [SNP; rs1695] in the GSTP1 gene and correlates them individually or in various combinations with the incidence of CP., Methods: A total of 203 clinically confirmed CP patients and 201 control subjects were enrolled from Multan and Dera Ghazi Khan Districts in Pakistan from April to July 2022. Multiplex Polymerase Chain Reaction (PCR) and tetra-primer amplification refractory mutation system-polymerase chain reaction (T-ARMS-PCR) approaches were applied to determine the genotypes of the studied GSTs. The association of rs1695 in GSTP1 with CP was studied both individually and in various combinations with GSTM1 and T1 ., Results: The absence of GSTM1 , the presence of GSTT1 and the presence of the mutant allele (G) at rs1695 in GSTP1 were found to be significantly associated with CP. Patients aged between 10 and 30 years were more affected by CP., Conclusion: Our results indicate that the genotypes of the analyzed GSTs affect the levels of protection from oxidative stress and may therefore influence the disease progression in CP.

Background: Studies have shown that glutathione S-transferase M1 ( GSTM1 ) and. glutathione S-transferase T1 (GSTT1) null genotype may increase the risk of cervical cancer (CC) or ovarian cancer (OC), however, the results of published original studies and meta-analyses are inconsistent. Objectives: To investigate the association between GSTM1 present/null and GSTT1 present/null polymorphisms, with the risk of cervical cancer or ovarian cancer. Methods: The odds ratios (ORs) and 95% confidence intervals (CIs) were used to assess the association between GSTM1 present/null and GSTT1 present/null polymorphisms and the risk of cervical cancer or ovarian cancer. To assess the confidence of statistically significant associations, we applied false positive reporting probability (FPRP) and bayesian false discovery probability (BFDP) tests. Results: Overall analysis showed that GSTM1 null was associated with an increased risk of cervical cancer, and subgroup analysis showed a significant increase in cervical cancer risk in Indian and Chinese populations; GSTT1 was not found null genotype are significantly associated with cervical cancer. Overall analysis showed that GSTM1 and GSTT1 null were not associated with the risk of ovarian cancer, subgroup analysis showed that GSTM1 null was associated with an increased risk of OC in East Asia, and GSTT1 null was associated with an increased risk of OC in South America. However, when we used false positive reporting probability and bayesian false discovery probability to verify the confidence of a significant association, all positive results showed "low confidence" (FPRP > .2, BFDP > .8). Conclusion: Overall, this study strongly suggests that all positive results should be interpreted with caution and are likely a result of missing plausibility rather than a true association., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Ye, Mu, Wang and He.)

Background: Our research aimed to clarify the role of genetic polymorphisms in GST (T1 and M1) in the development of Ph-ve CML., Materials and Methods: We report on a case-control study with 126 participants, divided into 26 patients with Ph-ve CML (57.7% male, 42.3% female) and 100 healthy volunteers (51% male, 49% female) with no medical history of cancer as a control population. All Ph-ve CML patients were diagnosed according to standard hematologic and cytogenetic criteria based on CBC, confirmed by Reverse Transcriptase Polymerase Chain Reaction (RT-PCR) to determine the presence or absence of the BCRABL gene, followed by bone marrow (BM) examination., Results: Of the 26 studied cases, 50% had the GSTT1 null genotype against 21% of the control group, a statistically significant difference (CI= 1.519 - 9.317; p-value= 0.004). The GSTM1 null genotype was detected in 23.1% of cases and 35% of controls, a difference not statistically significant (OR= 0.557; CI= 0.205-1.515; p-value= 0.252). The distribution of GSTT1 and GSTM1 polymorphisms was also examined according to gender, age and ethnic grouping; these findings revealed no statistically significant differences., Conclusion: Our study reveals a strong correlation between GSTT1 polymorphism and Ph-ve CML, whereas the data for GSTM1 polymorphisms indicates no role in the initial development of the disease. More studies are required to further clarify these and other genes' roles in disease development., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: Breast cancer is the most frequent oncological disease among women. Estrogens are known to play an important role in breast cancer development. Recognition of the relationship between polymorphisms within estrogen metabolizing genes and conventional prognostic factors of breast cancer might improve our knowledge on individualized breast cancer prognosis. Therefore, we aimed to investigate possible associations between germline genetic polymorphisms within GSTM1, GSTT1, GSTP1, SULT1A1 and UGT1A1 genes and breast cancer clinicopathological characteristics together with disease progression. Methods: Our study involved 80 young (younger than 50 years of age) breast cancer patients. PCR-based Restriction Fragment Length Polymorphism (RFLP) assay was used to determine GSTP1 and SULT1A1 genotypes. GSTM1 and GSTT1 null genotypes were detected by multiplex PCR. UGT1A1 polymorphism was investigated with microsatellite analysis. Relationships between genotypes and breast cancer clinicopathological features along with disease progression were estimated by Pearson's Chi-square test. Logistic regression analyses were performed to estimate the odds ratios associating different genotypes with clinicopathological characteristics and disease progression. Results: The study showed individuals with GSTT1 null genotype to have approximately 3.5 times higher risk for breast cancer progression than those with wild type genotype (OR = 3.472, 95% CI 1.043-11.559, P = 0.043). Moreover, SULT1A1 G638A AA genotype significantly increased the chances of HER2 molecular subtype breast cancer when compared to GG genotype (OR = 19.971, 95% CI 1.716-232.480, P = 0.017). Heterozygotes for GSTP1 A313G genotype were more likely to have positive lymph nodes in comparison to AA genotype carriers (OR = 2.803, 95% CI 1.049-7.487, P = 0.040). No significant correlation was determined for UGT1A1 A(TA)nTAA and GSTM1 +/- polymorphism alone or combined GTTT1 null and GSTM1 null genotype. Conclusions: Conclusively, our findings suggest that GSTT1 null genotype and SULT1A1 G638A AA genotype could be uselful genetic markers for breast cancer prognosis. Further analyses on larger sample size are required to highlight the effect of GSTP1 G allele on breast cancer prognosis. [ABSTRACT FROM AUTHOR]

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Background: Uterine myomas are benign tumors of the uterus and the most common solid pelvic tumors causing symptoms in approximately 25% of women in their reproductive years. However, its etiology and pathogenesis remain obscure; there is increasing evidence that endometriosis is inherited as a complex genetic trait. Recent studies indicated the involvement of glutathione S-transferase M1 (GSTM1) gene in the pathogenesis of this disease and current investigations are devoted to the other members of phase II detoxification system genes such as glutathione S-transferase T1 (GSTT1). Therefore, current study was carried out to investigate the distribution of GSTM1 and GSTT1polymorphisms in Iranian population in order to estimate possible impact of null-alleles of each gene in development of this disease. Methods: In this study, 50 patients with endometriosis diagnosed by both pathology and laparoscopic findings according to the revised American Fertility Society classification of endometriosis were recruited from subjects referred to the Pasteur Institute of Iran between November 2012 to September 2013. Accordingly, controls (n=50) were subjects without any of aforementioned gynecologic conditions. The genomic DNA was extracted from peripheral blood leucocytes using the salting out method and GSTM1 and GSTT1 genotyping for gene deletions were carried out using Gappolymerase chain re-action. Logistic regression analysis was applied to assess whether there was any significant risk increase between the case group with higher null genotypes compared to control group. The level of statistical significance was set at 0.05 and all analyses were conducted using the SPSS version 18.0 (SPSS Inc., Chicago, IL). Results: There was significant evidence that the distribution of the GSTM1 and GSTT1 genotypes differed between the patients and the controls with an allelic odds ratio (OR) of 3.56 (95%CI: 1.35-9.37, P=0.01) and 3.92 (95%CI: 1.4-10; P=0.009) respectively. Data analysis also revealed that individuals with both GSTM1 and GSTT1 null genotypes (-/-) had higher risk to develop the disease in comparison to the people with the both present (+/+) genotype (OR:19.23, P=0.007). Conclusion: The findings suggest that the GSTM1 and GSTT1 genetic polymorphisms are associated with the development of endometriosis in Iranian women which is in agreement with previous results obtained in other populations. However, the ethnic variations of polymorphisms should be evaluated in detail and differences should be incorporated into investigations of susceptibility variants for this disease. [ABSTRACT FROM AUTHOR]

GSTM1 and GSTT1 gene polymorphisms have been studied in many populations to evaluate their association with prostate cancer risk with contrasting results. The current study was aimed to find out the association of GSTM1 and GSTT1 gene polymorphisms with prostate cancer in Pakistani men. This case control study included pathologically confirmed prostate cancer patients and age matched male controls. Epidemiological data was collected by a standard questionnaire and presence or absence of GSTM1 and GSTT1 gene was observed by multiplex PCR using CYP1A1 as housekeeping gene. Prostate cancer was more prevalent in age of >60 years and most of the patients were at stage IV (70 %) and have undergone surgery. Family history of cancer, smoking, metastasis and surgery were found to be significant (P≤0.05) risk factors in prostate cancer development. Gleason score 7 was most prevalent (40.5 %) in prostate cancer patients. Source of drinking water, residential area, occupation, eating habits and number of family members had no association (P≥0.05) with prostate cancer risk. No significant association was found when comparing GSTM1 (OR=0.78) and GSTT1 (OR=0.89) gene deletions with prostate cancer risk. Smoking and TNM staging were also not associated with deletion of GSTM1 and GSTT1 genes. Comparison of dual null deletion of both genes with prostate cancer also showed non-significant associations. Deletion of GSTM1 gene at stage IV prostate cancer patients was significantly higher compared with other stages of cancer while no significance was shown by GSTT1 gene deletion. GSTM1, GSTT1 and deletion of both GSTM1 and GSTT1 genes do not contribute towards increased risk of prostate cancer in Pakistani population. [ABSTRACT FROM AUTHOR]

Objective We evaluated time to clearance of high risk (HR) HPV infection in relation to functional variants in three genes (CYP1A1, GSTT1, and GSTM1). Methods The study group consisted of 450 HR-HPV infected women from the Atypical squamous cells of undetermined significance-low-grade squamous intraepithelial Lesion Triage Study (ALTS) cohort followed up at the clinical center at Birmingham, Alabama. The Cox proportional hazard model with the Wei-Lin-Weisfeld (WLW) approach was used, controlling for relevant covariates. Results Women who were polymorphic for CYP1A1 experienced an HR-HPV clearance rate that was 20% (HR = 0.80, p = 0.04) lower than women without the polymorphism for CYP1A1, adjusting for all other cofactors. The GSTM1 null genotype was associated with higher HR-HPV clearance rate (HR = 1.39, p = 0.006). The polymorphism in GSTT1 was not significantly associated with time to clearance of HR-HPV. Conclusions Xenobiotic metabolism genes may influence the natural history of HR-HPV infection and its progression to cervical cancer. [ABSTRACT FROM AUTHOR]