Gene Summary

Gene:GSTM1; glutathione S-transferase mu 1
Aliases: MU, H-B, GST1, GTH4, GTM1, MU-1, GSTM1-1, GSTM1a-1a, GSTM1b-1b
Summary:Cytosolic and membrane-bound forms of glutathione S-transferase are encoded by two distinct supergene families. At present, eight distinct classes of the soluble cytoplasmic mammalian glutathione S-transferases have been identified: alpha, kappa, mu, omega, pi, sigma, theta and zeta. This gene encodes a glutathione S-transferase that belongs to the mu class. The mu class of enzymes functions in the detoxification of electrophilic compounds, including carcinogens, therapeutic drugs, environmental toxins and products of oxidative stress, by conjugation with glutathione. The genes encoding the mu class of enzymes are organized in a gene cluster on chromosome 1p13.3 and are known to be highly polymorphic. These genetic variations can change an individual's susceptibility to carcinogens and toxins as well as affect the toxicity and efficacy of certain drugs. Null mutations of this class mu gene have been linked with an increase in a number of cancers, likely due to an increased susceptibility to environmental toxins and carcinogens. Multiple protein isoforms are encoded by transcript variants of this gene. [provided by RefSeq, Jul 2008]
Databases:OMIM, VEGA, HGNC, Ensembl, GeneCard, Gene
Protein:glutathione S-transferase Mu 1
Source:NCBIAccessed: 28 February, 2015


What does this gene/protein do?
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Pathways:What pathways are this gene/protein implicaed in?
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Cancer Overview

GSTM1 is a glutathione S-transferase (GST) which play a role in the detoxification of metabolites of environmental carcinogens including tobacco smoke. There is some evidence to suggest that people with common polymorphisms of these genes may have an increased susceptibility to a range of different cancers. This susceptibility is often associated with a combined effect of other GST genes; GSTP1 and GSTT1. Polymorphisms in these genes have also been associated with pharacogenetics, toxicity to chemotherapy, and treatment outcome in some studies.

Research Indicators

Publications Per Year (1990-2015)
Graph generated 28 February 2015 using data from PubMed using criteria.

Literature Analysis

Mouse over the terms for more detail; many indicate links which you can click for dedicated pages about the topic.

Tag cloud generated 28 February, 2015 using data from PubMed, MeSH and CancerIndex

Specific Cancers (11)

Data table showing topics related to specific cancers and associated disorders. Scope includes mutations and abnormal protein expression.

Entity Topic PubMed Papers
Head and Neck CancersGSTM1 and Head and Neck Cancers View Publications248
Lung CancerGSTM1 and Lung Cancer View Publications236
Colorectal CancerGSTM1 and Colorectal Cancer View Publications142
Breast CancerGSTM1 and Breast Cancer View Publications137
Bladder CancerGSTM1 and Bladder Cancer View Publications128
Lung CancerTabacco smoke, GSTM1 Polymorphisms and Suceptability to Lung Cancer
There is some evidence to suggest that people with common polymorphisms of GSTM1 and other Glutathione S-transferase genes may have an increased susceptibility to lung cancer when exposed to Tobacco. In a case-control study of 136 NSCLC patients (Tang, 1998) results suggested that the effect of the GSTM1 null genotype is greatest in female smokers. Other research (Bennett, 1999) indicates that people with the GSTM1 null allele may be more suseptible to lung cancer on exposure to envoronmental tabacco smoke.
View Publications85
Prostate CancerGSTM1 and Prostate Cancer View Publications72
Oral Cavity CancerGSTM1 and Oral Cavity Cancer View Publications72
Acute Lymphocytic Leukemia (ALL), childGSTM1 Polymorphisms and Susceptibility to Leukemia Prognostic
Several studies have indicated significantly increased susceptibility to acuate leukemia, including childhood ALL, with a GSTM1 null genotype and also associated with GSTT1 polymorphisms.
View Publications23
Thyroid CancerGSTM1 and Thyroid Cancer View Publications19
Acute Lymphocytic Leukemia (ALL), childGSTM1 Polymorphisms and Treatment Response in Childhood Leukemia Therapy
Some studies indicate that polymorphisms in genes encoding enzymes involved in drug detoxification and metabolism (including STM1,GSTP1, MTHFR, MTRR) influence treatment responce in childhood acute lymphoblastic leukemia. For example Sepe et al (2012) found that MTRR A/G and GSTM1 null genotype, significantly increased the risk of relapse.
View Publications8

Note: list is not exhaustive. Number of papers are based on searches of PubMed (click on topic title for arbitrary criteria used).

Latest Publications: GSTM1 (cancer-related)

Chirilă DN, Bălăcescu O, Popp R, et al.
GSTM1, GSTT1 and GSTP1 in patients with multiple breast cancers and breast cancer in association with another type of cancer.
Chirurgia (Bucur). 2014 Sep-Oct; 109(5):626-33 [PubMed] Related Publications
INTRODUCTION: breast cancer has the highest incidence in women.Glutathione S-transferases (GSTs) are a large group of enzymes involved in the metabolism of xenobiotics. The members of this gene superfamily are involved in the development of multiple cancers.
OBJECTIVES: the aim of the study was to see whether the GSTM1, GSTT1 and GSTP1 genetic polymorphisms are risk factors for patients diagnosed with multiple malignancies, of which at least one is located in the breast.
MATERIALS AND METHODS: in the period between 2005 and 2012,of the 520 patients diagnosed with breast cancer, 69 had multiple primitive malignant tumors, of which at least one was localized in the breast. The research on GSTM1, GSTT1 and GSTP1 genotypes consisted of 59 patients diagnosed with multiple breast cancers or with breast cancer in association with another type of cancer, compared with a group of healthy controls.
RESULTS: in the subgroup of patients with breast cancer in association with another type of cancer, the GSTM1 null genotype was present in 61.2% of patients, compared to 29% of controls; the subgroup of metachronous breast cancers, the presence of any of the GSTT1 or GSTM1 null genotypes was statistically significantly different from that of controls (65.2%vs. 28.5%); in the subgroup with synchronous cancers, the GSTM1 null genotype was found in 66.6% of patients compared to 9% for the controls, and the presence of any null genotype (GSTM1 and GSTT1) was also statistically significant in the case group.
CONCLUSIONS: the GSTM1 null genotype is a risk factor for synchronous breast cancers and for breast cancer associated with extramammary cancer; the presence of null genotypes(GSTM1 or GSTT1) is a risk factor for multiple breast cancer(bilateral or synchronous); the GSTT1 null genotype and the heterozygous variant allele (Ile105Val) and homozygous variant allele (Val105Val) of GSTP1 are not risk factors for the cases studied.

Sun X, Guo M, Sun Q, et al.
The existence and role of microchimerism after microtransplantion.
Leuk Res. 2014; 38(11):1285-90 [PubMed] Related Publications
AIM: To study microchimerism's role and function after microtransplantation and identify novel genetic markers for microchimerism detection.
METHODS: Analyzing microchimerisms from patients microtransplanted to determine the presence of GSTT1, GSTM1, SRY and other genetic markers by real-time PCR.
RESULTS: Microchimerism could be detected for a short time after microtransplantation simultaneously with hematopoietic recovery. In conclusion, microchimerism might accelerate hematopoietic recovery and GSTT1 and GSTM1 genes could be used as genetic markers to differentiate donor cells.
DISCUSSION: Microchimerism could exist for a short time after microtransplantation and appears to function in hematopoietic recovery. According to published reports, cytokines secreted from microchimerisms could be detected in recipients and exhibit some function on the host. Therefore, cytokines secreted from donor cells are hypothesized to accelerate hematopoietic recovery. The evidence to prove a longer existence for microchimerism is insufficient and needs supports by additional experiments; however, we cannot deny its existence just because of the limited sensitivity of methods.

Davies A, Giannoudis A, Zhang JE, et al.
Dual glutathione-S-transferase-θ1 and -μ1 gene deletions determine imatinib failure in chronic myeloid leukemia.
Clin Pharmacol Ther. 2014; 96(6):694-703 [PubMed] Related Publications
Approximately 40% of patients with chronic myeloid leukemia (CML) receiving imatinib fail treatment. There is an increased risk of CML in subjects with (i) deletions of genes encoding glutathione-S-transferase (GST)-θ1 (GSTT1) and -μ1, (GSTM1) and (ii) the GST-π1 (GSTP1) single-nucleotide polymorphism (SNP) Ile105Val (GSTP1*B; rs1695); however, their effects on imatinib treatment outcome are not known. Here, we assess the role of these GSTs in relation to imatinib treatment outcome in 193 CML patients. Deletion of GSTT1 alone, or in combination with deletion of the GSTM1 gene, significantly increased the likelihood of imatinib failure (P = 0.021 and P < 0.001, respectively). The GSTP1*B SNP was not associated with time to imatinib failure. Losses of the GSTT1 and GSTM1 genes are therefore important determinants of imatinib failure in CML. Screening for GSTT1 and GSTM1 gene deletions during diagnosis may identify patients who may be better treated using an alternative therapy.

He HR, You HS, Sun JY, et al.
Glutathione S-transferase gene polymorphisms and susceptibility to acute myeloid leukemia: meta-analyses.
Jpn J Clin Oncol. 2014; 44(11):1070-81 [PubMed] Related Publications
OBJECTIVE: A large body of evidence has shown the possible relevance of polymorphisms of the genes that encode glutathione S-transferase μ, π and θ (GSTM1, GSTP1 and GST1, respectively) to the susceptibility of acute myeloid leukemia, but the exact association still remains uncertain. Therefore, we performed a meta-analysis to derive a more precise estimation of the relationship.
METHODS: A comprehensive literature search of PubMed and Web of Knowledge electronic databases was conducted to collect relevant studies until 20 February 2014. References of the retrieved articles were also screened. The extracted data were statistically analyzed, and pooled odds ratios with 95% confidence intervals were calculated to estimate the association strength using Review Manager version 5.2.
RESULTS: Twenty-nine studies were included in the meta-analysis. The pooled analyses revealed that the GSTM1-null genotype was associated with an increased risk of acute myeloid leukemia in East Asians (P = 0.01; odds ratio = 1.22; 95% confidence interval = 1.05-1.42), and GSTT1-null genotype in Caucasians (P < 0.0001; odds ratio = 1.48; 95% confidence interval = 1.29-1.69). There was also a predilection towards the female gender for both of these polymorphisms. For GSTP1 Ile105Val polymorphism, no significant association was found under any contrast model. In addition, the presence of the double-null genotypes increased the risk of acute myeloid leukemia in both Caucasians and East Asians.
CONCLUSIONS: This meta-analysis suggested that heritable GST status could influence the risk of developing acute myeloid leukemia.

Xiao Q, Deng D, Li H, et al.
GSTT1 and GSTM1 polymorphisms predict treatment outcome for acute myeloid leukemia: a systematic review and meta-analysis.
Ann Hematol. 2014; 93(8):1381-90 [PubMed] Related Publications
Glutathione S-transferases (GSTs) contribute to the metabolism of different xenobiotics and anticancer drugs and confer protection against oxidative stress thus may influence the treatment outcome of acute myeloid leukemia (AML). Studies regarding the association between GSTT1 and GSTM1 polymorphisms and treatment outcome in AML patients showed an inconsistent result. A systematic review and meta-analysis were performed to further explore this association. PubMed, Hartford User Group Exchange (HUGE), and China National Knowledge Infrastructure (CNKI) databases were searched for all related publications. Statistical analyses were analyzed by using RevMan 5.0 and Stata 9.0 softwares. A total of 1,837 patients in 11 studies were included. GSTT1 null genotype was found to be significantly associated with a reduced response after first course of induction chemotherapy (odds ratio (OR) = 0.894, 95 % confidence interval (CI) = 0.818-0.977, P = 0.013), progression-free survival (PFS; hazard ratio (HR) = 0.698, 95 % CI = 0.520-0.937, P = 0.017), and overall survival (OS; HR = 0.756, 95 % CI = 0.618-0.925, P = 0.007) in Asian population. GSTM1/GSTT1 double-null genotype was also identified to be significantly associated with response after the first course of induction chemotherapy (OR = 0.40, 95 % CI = 0.24-0.67, P = 0.0003). Our study suggested that GSTT1 null genotype and GSTT1/GSTM1 double-null genotype were associated with a worse treatment outcome for AML patients, especially in Asian population.

Li W, Song LQ, Tan J
Combined effects of CYP1A1 MspI and GSTM1 genetic polymorphisms on risk of lung cancer: an updated meta-analysis.
Tumour Biol. 2014; 35(9):9281-90 [PubMed] Related Publications
Genetic polymorphisms of cytochrome P450 1A1 (CYP1A1) and glutathione S-transferase M1 (GSTM1) genes might contribute to the variability in individual susceptibility to lung cancer, but the reported results from individual studies are not always consistent. We therefore conducted a meta-analysis to systematically estimate the associations between polymorphisms of these two genes and risk of lung cancer. Twenty-one studies with 8,926 subjects were finally enrolled into this study. Meta-analysis was performed by RevMan 5.2. Odds ratio (OR) and its 95 % confidence interval (CI) were calculated to evaluate the susceptibility to lung cancer. Compared with the wild-type homozygous genotype, significantly elevated risk of lung cancer were associated with variant CYP1A1 MspI (m1/m2 + m2/m2 vs. m1/m1: OR = 1.27, 95 % CI = 1.12-1.43, P < 0.001) and deletion of GSTM1 (null vs. present: OR = 1.26, 95 % CI = 1.13-1.40, P < 0.001). Both the two genetic polymorphisms were independently associated with the risk of lung cancer. The pooled OR of lung cancer for population with both CYP1A1 MspI and GSTM1 mutations (MspI m1/m2 or m2/m2 and GSTM1 null) was 1.62 (95 % CI 1.27-2.07, P < 0.001) when compared with those without any of the above mutations, which is higher than single genetic polymorphism. In the stratified analysis, significantly higher risks of lung cancer associated with above genetic polymorphisms were found only in Asian population. This meta-analysis suggests that the CYP1A1 MspI and GSTM1 polymorphisms correlate with increased lung cancer susceptibility independently, and that there is an interaction between the two genes. However, the associations vary in different ethnic populations.

Reszka E, Jablonowski Z, Wieczorek E, et al.
Polymorphisms of NRF2 and NRF2 target genes in urinary bladder cancer patients.
J Cancer Res Clin Oncol. 2014; 140(10):1723-31 [PubMed] Free Access to Full Article Related Publications
PURPOSE: NRF2 transcription factor is involved in modulation of various antioxidant and metabolic genes and, therefore, may modulate anti-carcinogenic potential. Association between polymorphisms of NRF2 and five NRF2-regulated genes and urinary bladder cancer (BC) risk was analyzed.
METHODS: The study group included 244 BC patients, while the control group comprised 365 individuals with no evidence of malignancy. Genotyping of GSTM1 (deletion), GSTT1 (deletion), GSTA1 -69C/T (rs3957357), GSTP1 Ile105Val (rs1695), SOD2 Ala16Val (rs4880) and NRF2 -617C/A (rs6721961) in blood genomic DNA was performed by means of real-time PCR assays. The associations between gene polymorphism and BC risk were computed by logistic regression.
RESULTS: The frequency of GSTA1, GSTP1, SOD2 and NRF2 genotypes did not differ in both groups. A significantly higher BC risk was associated with GSTM1 null genotype after adjusting to age, sex and smoking habit (OR 1.85, 95 % CI 1.30-2.62; P = 0.001). GSTT1 null (OR 0.50, 95 % CI 0.31-0.81; P = 0.005) and GSTP1 Val105Val (OR 0.52, 95 % CI 0.27-0.98; P = 0.04) genotypes were associated with reduced BC risk separately or in combination (OR 0.24, 95 % CI 0.11-0.51; P < 0.0001) (P heterogeneity = 0.01). Combined GSTT1 null and SOD2 with at least one 16Val allele among never smokers encompass reduced BC risk (OR 0.14, 95 % CI 0.03-0.63; P = 0.01) (P heterogeneity = 0.04).
CONCLUSIONS: This study supports hypothesis that GSTM1 null genotype may be a moderate BC risk factor. The gene-gene and gene-environment interactions associated with combined GSTP1/GSTT1 and combined GSTT1/SOD2 genetic polymorphisms along with cigarette smoking habit may play a significant role in BC risk modulation.

Zi Y, Wu S, Ma D, et al.
Association of GSTTI and GSTM1 variants with acute myeloid leukemia risk.
Genet Mol Res. 2014; 13(2):3681-5 [PubMed] Related Publications
We aimed to investigate the relationships between polymorphisms of the glutathione S-transferases (GSTs) GSTM1, GSTTI, and GSTP1 and the risk of developing acute myeloid leukemia (AML). A total of 206 AML cases and 231 controls were collected for our study. The genotyping of GSTs (GSTM1, GSTTI, and GSTP1) was based upon the duplex polymerase chain reaction with the confronting two-pair primer (PCR-CTPP) method. Individuals carrying null GSTTI and GSTM1 genotypes had a 1.52- and 1.78-fold increased risk of developing acute leukemia, respectively, compared to non-null genotype carriers (P < 0.05). A high risk was observed in those carrying a combination of null genotypes of GSTM1 and GSTTI with GSTP1-Val allele genotypes when compared with those carrying wild-type genotypes, with an odds ratio (95% confidence interval) of 3.62 (1.53-8.82) (P < 0.05). These findings indicate that genetic variants of GSTTI and GSTM1 significantly increase the risk of developing AML. Our study offers important insights into the molecular etiology of AML.

Sui C, Ma J, He X, et al.
Interactive effect of glutathione S-transferase M1 and T1 polymorphisms on hepatocellular carcinoma.
Tumour Biol. 2014; 35(8):8235-41 [PubMed] Related Publications
Glutathione S-transferase M1 (GSTM1) and T1 (GSTT1) have been involved in the risk of hepatocellular carcinoma (HCC). However, the interactive effect of GSTM1 and GSTT1 has not been reported previously. The aim of this work was to investigate the interaction and synergism of their variants. We identified nine publications including 1,085 cases and 2,396 controls containing both GSTM1 and GSTT1, and the bi-factor variance analysis of equal repeated test, binary class logistic regression analysis, meta-analysis and probability method were used in this analysis. Data showed there was no interaction between GSTM1 and GSTT1 null genotype variation in HCC development. In addition, individuals with at least one null genotype of GSTM1 and GSTT1 had higher susceptibility to HCC (OR = 2.99, 95 % CI 2.21-4.02). In the control group, the probability of individuals with at least one null genotype of GSTM1 and GSTT1 was 0.6624, while in the case group, the probability to develop HCC with at least one null genotype of GSTM1 and GSTT1 increased to 0.1760, which was considered as the changing characteristics of HCC occurrence in Chinese population. Our result suggests that there would be no direct interaction of GSTM1 and GSTT1 genotype in HCC risk. We speculate that GSTM1 and GSTT1 genotype variations have their own independent function in HCC development and may mutate independently to cause HCC. The synergism variants of the two genes in HCC development have bigger risk in Chinese population.

Kap EJ, Richter S, Rudolph A, et al.
Genetic variants in the glutathione S-transferase genes and survival in colorectal cancer patients after chemotherapy and differences according to treatment with oxaliplatin.
Pharmacogenet Genomics. 2014; 24(7):340-7 [PubMed] Related Publications
INTRODUCTION: The glutathione S-transferase (GST) enzymes are involved in the detoxification of a range of carcinogenic compounds as well as chemotherapeutic agents. Therefore, genetic variants in the GST genes could influence survival in patients with colorectal cancer (CRC). Results from previous studies have been inconsistent and therefore we investigated the association between the GSTP1 ile105val polymorphism and the copy number variants of the GSTM1 and GSTT1 genes and survival in CRC patients treated with adjuvant/palliative chemotherapy.
PATIENTS AND METHODS: We included 755 CRC patients with stage II-IV disease from two population-based studies carried out in Germany. Genotyping of the GSTP1 polymorphism was carried out using fluorescence-based melting curve analysis and copy number variants were determined using a multiplex PCR. Survival analysis was carried out using the Cox regression model, adjusting for age, sex, UICC stage, cancer site, and radiation therapy.
RESULTS: Compared with noncarriers, CRC patients who were homozygote carriers of GSTM1 had significantly poorer survival after treatment with oxaliplatin [hazard ratio (HR) 2.25, 95% confidence interval (CI) 0.93-5.44] than those not treated with oxaliplatin (HR 0.64, 95% CI 0.30-1.34; P for heterogeneity=0.031). The association was significant in metastatic CRC patients treated with oxaliplatin (HR 3.59, 95% CI 1.29-10.03). Neither the GSTP1 105val allele nor the GSTT1 deletion was significantly associated with CRC survival.
CONCLUSION: Our data suggest that GSTM1 may be a predictive marker for oxaliplatin therapy; however, independent large studies are warranted to confirm these results.

Wan G, Li F, Li W, et al.
[Glutathione S-transferase M1 polymorphism and susceptibility to breast cancer in Chinese population: a meta-analysis].
Zhonghua Bing Li Xue Za Zhi. 2014; 43(3):158-62 [PubMed] Related Publications
OBJECTIVE: To evaluate the published data on association between present/null polymorphism of glutathione S-transferase M1 (GSTM1) and breast cancer risk in Chinese population in order to abttain a more precise and comprehensive estimation of the relationship.
METHODS: A meta-analysis was performed to investigate the association between GSTM1 polymorphism and susceptibility to breast cancer in Chinese population by searching Pubmed, Embase, Cochrane library, CNKI, VIP, Wanfang and CBD database. The data were screened according to the inclusion and exclusion criteria, and extracted, and the quality of included studies was evaluated. The pooled odds ratios (OR) with 95% confidence intervals (95%CI) were calculated using RevMan 5.2 and Stata 12.0 software. Publication bias and sensitivity analysis were also assessed.
RESULTS: A total of 15 case-control studies involving 5,176 cases and 5 890 controls were included in the meta-analysis. The results showed that individuals with GSTM1 null genotype harbored a significantly increased risk of breast cancer compared to that with GSTM1 non-null genotype in Chinese population (OR=1.34, 95%CI=1.12-1.60, P=0.002). The subgroup analysis by region revealed that the individuals with GSTM1 null genotype were significantly associated with an increased risk of breast cancer in southern and northern China populations (southern: OR=1.14, 95%CI=1.01-1.28, P=0.03; northern: OR=2.65, 95%CI=2.04-3.34, P<0.01).
CONCLUSION: The current meta-analysis demonstrates that the GSTM1 polymorphism is significantly associated with susceptibility to breast cancer in Chinese population, and the GSTM1-deficit may increase the risk of breast cancer.

Mikhalenko EP, Krupnova ÉV, Chakova NN, et al.
[Evaluation of connection of combinations of polymorphic variants of genes of xenobiotic metabolizing enzymes with a predisposition to lung cancer].
Tsitol Genet. 2014 Mar-Apr; 48(2):52-9 [PubMed] Related Publications
Imbalance between the phases of the biotransfotmation system (activation, detoxication and removal of toxic compounds) is one of the causes of multifactorial pathology developing. That is why study on the influence of the total contribution of polymorphic gene variants of xenobiotic biotransformation enzymes of all three phases on predisposition to lung cancer emergence is important. The aim of the work was to determine polymorphic variants of genes of xenobiotic biotransformation enzymes of lung cancer patients and to identify markers of predisposition to lung cancer. Association of homozygous GSTT1 gene deletion with predisposition to lung cancer was detected in residents of Belarus. Combinations of polymorphic gene loci of biotransformation enzymes exert a modifying effect on risk importance of GSTT1 genotype in lung cancer development. The combination 734AA CYP1A2/GSTT1(-)/GSTM1(+)/"slow" acetylator/3435CC MDR1 is of the highest risk importance. The combination "slow" acetylator/GSTT1(+)/ GSTM1(+) exerts a protective effect.

Stosic I, Grujicic D, Arsenijevic S, et al.
Glutathione S-transferase T1 and M1 polymorphisms and risk of uterine cervical lesions in women from central Serbia.
Asian Pac J Cancer Prev. 2014; 15(7):3201-5 [PubMed] Related Publications
The aim of this study was to investigate the frequencies of GSTT1 and GSTM1 deletion polymorphisms in newly-diagnosed patients with uterine cervical lesions from central Serbia. Polymorphisms of GST genes were genotyped in 97 patients with cervical lesions and 50 healthy women using a multiplex polymerase chain reaction (PCR). The GSTM1 null genotype was significantly more prominent among the patients than in controls (74.2% vs 56.0%), the risk associated with lesions being almost 2.3-fold increased (OR=2.26, 95%CI=1.10-4.65, p=0.03) and 3.17-fold higher in patients above >45 years old (95%CI=1.02-9.79, p=0.04). The analysis of the two genotypes demonstrated that GSTM1 null genotype significantly increased risk only for low grade squamous intraepithelial lesion-LSIL (OR=2.81, 95%CI=1.03-7.68, p=0.04). GSTT1 null genotype or different genotype combinations were not found to be risk factors, irrespective to lesion stages, age or smoking. We found that the risk of cervical lesions might be significantly related to the GSTM1 null genotype, especially in women aged above 45 years. Furthermore, the GSTM1 polymorphism might have greater role in development of early stage lesions.

Pan C, Zhu G, Yan Z, et al.
Glutathione S-transferase T1 and M1 polymorphisms are associated with lung cancer risk in a gender-specific manner.
Oncol Res Treat. 2014; 37(4):164-9 [PubMed] Related Publications
BACKGROUND: Glutathione S-transferase (GST) T1 and M1 are detoxification enzymes which neutralize various carcinogenic compounds. Polymorphisms of the GSTT1 and GSTM1 genes which encode the enzymes could be associated with cancer risk.
PATIENTS AND METHODS: We investigated the association of GSTT1 and GSTM1 null polymorphisms with lung cancer risk in a tightly matched, considerably large sample in China. Genotyping was performed utilizing polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis and DNA sequencing, and associations were measured by using logistic regression analysis.
RESULTS: We found that the null genotypes of both polymorphisms resulted in an increased lung cancer risk, with an odds ratio (OR) of 1.57 (95% confidence interval (CI) 1.23-2.00) for GSTT1 and OR 1.87 (95% CI 1.46-2.39) for GSTM1 (p < 0.01). Significant associations remained after stratification by histopathology (p < 0.01) and smoking status (p < 0.05). When gender-stratified association was performed, we found that the GSTT1 null genotype resulted in an increased risk among males (adjusted OR 2.95, 95% CI 2.07-4.20; p < 0.01) but not females (p > 0.05), while the GSTM1 null genotype resulted in an increased risk among females (adjusted OR 2.18, 95% CI 1.54-3.10; p < 0.01) but not males (p < 0.05).
CONCLUSION: Polymorphisms in GSTT1 and GSTM1 are associated with the risk of lung cancer in a gender-specific manner.

Lippmann D, Lehmann C, Florian S, et al.
Glucosinolates from pak choi and broccoli induce enzymes and inhibit inflammation and colon cancer differently.
Food Funct. 2014; 5(6):1073-81 [PubMed] Related Publications
High consumption of Brassica vegetables is considered to prevent especially colon carcinogenesis. The content and pattern of glucosinolates (GSLs) can highly vary among different Brassica vegetables and may, thus, affect the outcome of Brassica intervention studies. Therefore, we aimed to feed mice with diets containing plant materials of the Brassica vegetables broccoli and pak choi. Further enrichment of the diets by adding GSL extracts allowed us to analyze the impact of different amounts (GSL-poor versus GSL-rich) and different patterns (broccoli versus pak choi) of GSLs on inflammation and tumor development in a model of inflammation-triggered colon carcinogenesis (AOM/DSS model). Serum albumin adducts were analyzed to confirm the up-take and bioactivation of GSLs after feeding the Brassica diets for four weeks. In agreement with their high glucoraphanin content, broccoli diets induced the formation of sulforaphane-lysine adducts. Levels of 1-methoxyindolyl-3-methyl-histidine adducts derived from neoglucobrassicin were the highest in the GSL-rich pak choi group. In the colon, the GSL-rich broccoli and the GSL-rich pak choi diet up-regulated the expression of different sets of typical Nrf2 target genes like Nqo1, Gstm1, Srxn1, and GPx2. GSL-rich pak choi induced the AhR target gene Cyp1a1 but did not affect Ugt1a1 expression. Both colitis and tumor number were drastically reduced after feeding the GSL-rich pak choi diet while the other three diets had no effect. GSLs can act anti-inflammatory and anti-carcinogenic but both effects depend on the specific amount and pattern of GSLs within a vegetable. Thus, a high Brassica consumption cannot be generally considered to be cancer-preventive.

Ghosh SK, Singh AS, Mondal R, et al.
Dysfunction of mitochondria due to environmental carcinogens in nasopharyngeal carcinoma in the ethnic group of Northeast Indian population.
Tumour Biol. 2014; 35(7):6715-24 [PubMed] Related Publications
Nasopharyngeal carcinoma (NPC) is a rare cancer worldwide, but in India, NPC is uncommon in its subcontinent except in the north-eastern part of the country. NPC is thought to be caused by the combined effects of environmental carcinogens, genetic susceptibility and Epstein-Barr virus (EBV). This is the first study that aimed to examine the selected risk factors, mostly dietary, viral environmental, metabolic gene polymorphisms, mitochondrial DNA (mtDNA) copy number variation and their risk, in subjects who are highly prone to NPC in the ethnic groups of Northeast India, which has included cases, first-degree relatives and controls. The cases and controls were selected from three ethnic groups (Manipuri, Naga and Mizo) of Northeast India with high prevalence of NPC. This case-control family study includes 64 NPC patients, 88 first-degree relatives and 100 controls having no history of cancer. PCR-based detection was done for EBV-latent membrane protein 1 (LMP1) gene and glutathione S-transferase Mu 1 (GSTM1)-glutathione S-transferase theta 1 (GSTT1) polymorphism. A comparative ΔCt method was used for the determination of mtDNA content. An increased risk of 2.00-6.06-folds to NPC was observed with those who intake smoked meat and fish, salted fish and fermented fish; betel nut chewers; tobacco smokers; alcohol drinkers; and those who have kitchen inside the living room, glutathione S-transferase null genotype and EBV infection. The risk of NPC increased in cases with decreased mtDNA copy number (P trend = 0.007). A significant difference between GST null genotypes and EBV infection with mtDNA content was found in the cases (P < 0.0001). The understandings of environment-genetic risk factors and their role in the etiology of NPC are helpful as preventive measures and screening.

Zhao Y, Zeng J, Zhang Y, et al.
GSTM1 polymorphism and lung cancer risk among East Asian populations: a meta-analysis.
Tumour Biol. 2014; 35(7):6493-500 [PubMed] Related Publications
GSTM1 gene encodes a key enzyme involved in the metabolism of xenobiotics, and its polymorphisms have been related to individual susceptibility to several malignancies. Many molecular epidemiological studies were performed to investigate the association between the GSTM1 null polymorphism and lung cancer susceptibility in East Asia. However, the results were inconsistent. In order to derive a more precise estimation, we conducted this meta-analysis involving 5,909 lung cancer cases and 7,067 controls from 35 studies. We used crude odds ratios (ORs) with 95 % confidence intervals (CIs) to assess the association between GSTM1 null genotype and the risk of lung cancer. Our study found that the GSTM1 null genotype appeared to be a significant risk factor for lung cancer in East Asia population (OR = 1.30, 95 % CI = 1.17-1.45, P heterogeneity < 0.0001, and I (2) = 54.0 %).

Al-Achkar W, Azeiz G, Moassass F, Wafa A
Influence of CYP1A1, GST polymorphisms and susceptibility risk of chronic myeloid leukemia in Syrian population.
Med Oncol. 2014; 31(5):889 [PubMed] Related Publications
In the present study, we investigated the associations of polymorphisms in cytochrome P450 gene (CYP1A1), glutathione S-transferase genes (GSTM1 and GSTT1) with chronic myelogenous leukemia (CML). A total of 126 patients with CML and 172 healthy volunteers were genotyped, and the DNA was isolated from their blood samples. The polymorphisms were assessed by polymerase chain reaction (PCR) restriction fragment length polymorphism-based methods and multiplex PCR. Logistic regression analyses showed significant risk of CML associated with CYP1A1 Val allele [odds ratio (OR) 3.3, 95% confidence intervals (CI) 1.96-5.53], (p < 0.0001) while CYP1A1 Val/Val homozygotes were observed only in the CML patients. There was statistically significant difference in the frequency of GSTM1 and GSTT1 null genotypes. The GSTT1-null genotype was slightly higher in 27% of CML cases and 16.7% of controls (OR 1.98, 95% CI 1.12-3.5) (p < 0.020). The GSTM1 null was higher in 42.8% of CML cases and 22.7% of controls (OR 2.55, 95% CI 1.54-4.22) (p < 0.00024). The individuals carrying CYP1A1 Ile/Val (AG) and GSTM1 null genotype have 9.9 times higher risk to be CML than those carrying CYP1A1 Ile/Ile (AA) and GSTM1 present genotype (OR 9.9, 95% CI 2.7-36.3) (p < 0.0001). This suggests that the association of the GSTM1 null genotype, either alone or in combination with GSTT1 null, with CYP1AI heterozygous leads to the CML risk.

He HR, Zhang XX, Sun JY, et al.
Glutathione S-transferase gene polymorphisms and susceptibility to chronic myeloid leukemia.
Tumour Biol. 2014; 35(6):6119-25 [PubMed] Related Publications
Glutathione S-transferase (GST), a phase II metabolizing enzyme, plays an important role in the cellar defense system, and its activity may modulate leukemia risk. A large body of evidence has shown the possible relevance of functional polymorphisms of the genes that encode GSTs μ, π, and θ (GSTM1, GSTP1, and GST1, respectively) to the genetic susceptibility of chronic myeloid leukemia (CML). Because of the lack of available conclusive data, we performed a meta-analysis of all relevant available studies to derive a more precise estimation of the relationship. A comprehensive literature search of PubMed and Web of Knowledge electronic databases was conducted to collect relevant studies until December 20, 2013, and the extracted data were statistically analyzed using Review Manager version 5.2. Finally, 16 eligible studies were identified in the literature. The GSTT1 null genotype was associated with an increased risk of CML, as were the double null GSTT1 and GSTM1 genotypes. These findings suggest that heritable GST status influences the risk of developing CML and that more attention should be paid to carriers of these susceptibility genes.

Zhang Y, Chen W, Ji JF, et al.
GSTM1 null polymorphisms is associated with laryngeal cancer risk: a meta-analysis.
Tumour Biol. 2014; 35(7):6303-9 [PubMed] Related Publications
Many studies have examined the association between the GSTM1 (null or non-null genotype) polymorphism and laryngeal cancer risk in various populations, but their results have been inconsistent. To assess this relationship more precisely, a meta-analysis was performed. PubMed was searched for case-control studies published up to December 2013. Data were extracted and pooled odds ratios (OR) with 95 % confidence intervals (CI) were calculated. Ultimately, 23 studies, comprising 2,562 laryngeal cancer cases and 4,091 controls, were included. Overall, for null versus present, the pooled OR was 1.22 (95 % CI = 1.10-1.36), and the heterogeneity was found in all studies. In the stratified analysis by ethnicity, significant risks were found among Asians (OR = 1.71; 95 % CI = 1.34-2.19; P = 0.011 for heterogeneity) and in Caucasians (OR = 1.13, 95 % CI = 1.00-1.27; P = 0.036 for heterogeneity). In conclusion, this meta-analysis demonstrates that the GSTM1 null gene polymorphism is an increased risk of laryngeal cancer in Asians and Caucasians.

Oliveira AL, Oliveira Rodrigues FF, Dos Santos RE, et al.
 GSTT1, GSTM1, and GSTP1 polymorphisms as a prognostic factor in women with breast cancer.
Genet Mol Res. 2014; 13(2):2521-30 [PubMed] Related Publications
The glutathione S-transferase (GST) family comprises phase-II cellular detoxification enzymes that catalyze the conjugation of chemotherapy drugs to glutathione and act on the apoptotic pathway. The aim of this study was to determine whether polymorphisms of the GSTT1, GSTM1, and GSTP1 genes are associated with different rates of overall survival (OS) and disease-free survival (DFS) after neoadjuvant chemotherapy in the management of locally advanced breast cancer, using either simple or combined analyses, and in relation to the post-therapy axillary lymph node status. Forty women with invasive ductal carcinoma of the breast submitted to neoadjuvant chemotherapy with 5-fluorouracil, epirubicin, and cyclophosphamide were genotyped for GSTT1, GSTM1, and GSTP1. Comparisons were performed for the three genes, either isolated or in pairs, in polymorphic or wild-type combinations. Finally, the OS and DFS of patients were analyzed with respect to axillary lymph node status and with respect to wild-type or polymorphic presentations of each gene. No statistically significant difference in OS and DFS was evident between women with wild-type or polymorphic forms of the genes, either isolated or in pairs, after neoadjuvant chemotherapy. By contrast, after treatment, lymph node-negative women had better OS and DFS only in the presence of polymorphisms of GSTP1, and improved DFS only in the presence of the polymorphic types of GSTT1 and GSTM1 compared to women with positive lymph nodes. The presence of polymorphic forms of GSTP1, GSTM1, and GSTT1 was crucial to conferring better OS and DFS among women with negative axillary lymph nodes.

Silva TM, Marques CR, Marques Filho MF, et al.
Association of the GSTT1 polymorphism in upper aerodigestive tract cancer with tobacco smoking.
Genet Mol Res. 2014; 13(1):528-37 [PubMed] Related Publications
Polymorphisms in genes encoding xenobiotic-metabolizing enzymes might explain differences in the susceptibility to upper aerodigestive tract (UADT) cancers in individuals exposed to tobacco or other carcinogens. The present study aimed to evaluate the association of polymorphisms in the glutathione S-transferase (GST) candidate genes GSTM1, GSTT1, and GSTP1 with the risk of UADT cancers. GST gene polymorphisms were determined in 116 individuals with UADT cancer and 224 healthy controls using polymerase chain reaction-based methods. The GSTT1-null polymorphism was found to be a protective factor for UADT cancer [(odds ratio (OR) = 0.5, 95% confidence interval (CI) = 0.27-0.93)], although this association was not confirmed when adjusted for gender, age, smoking, alcoholism, and self-reported skin color in the multivariate logistic regression model (OR = 0.61, 95%CI = 0.29-1.28). The combined effect of GSTT1-positive genotypes with either the GSTP1 wild-type genotype (Ile/Ile) or the GSTP1 variant genotypes (Ile/Val or Val/Val) increased the risk for UADT cancer (OR = 4.34, 95%CI = 1.06-17.78 and OR = 4.55, 95%CI = 1.12-18.42, respectively). A significant interaction was observed among moderate smokers carrying the GSTT1-positive genotype. In this population, the significant gene-gene and gene-environment interactions of GST polymorphisms may confer a substantial risk to UADT cancers.

Yamada I, Matsuyama M, Ozaka M, et al.
Lack of associations between genetic polymorphisms in GSTM1, GSTT1 and GSTP1 and pancreatic cancer risk: a multi-institutional case-control study in Japan.
Asian Pac J Cancer Prev. 2014; 15(1):391-5 [PubMed] Related Publications
BACKGROUND: We aimed to evaluate the role of genetic polymorphisms in tobacco carcinogen-metabolizing genes and their interactions with smoking in a hospital-based case-control study of Japanese subjects.
MATERIALS AND METHODS: We examine the associations of pancreatic cancer risk with genetic polymorphisms in GSTM1, GSTT1 and GSTP1, phase II enzymes that catalyze the conjugation of toxic and carcinogenic electrophilic molecules. The study population consisted of 360 patients and 400 control subjects, who were recruited from several medical facilities in Japan. Unconditional logistic regression methods were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the associations between genotypes and pancreatic cancer risk.
RESULTS: Among the control subjects, the prevalence of the GSTM1-null genotype and the GSTT1-null genotype was approximately 56% and 48%, respectively. Cases and controls were comparable in terms of GSTM1 and GSTT1 genotype distributions. Neither of the deleted polymorphisms in GSTM1 and GSTT1 was associated with the risk of pancreatic cancer, with an age- and sex-adjusted OR of 0.99 (95%CI: 0.74-1.32) for the GSTM1-null genotype, and 0.98 (95%CI: 0.73-1.31) for the GSTT1-null genotype. The OR was 0.97 (95%CI: 0.64-1.47) for individuals with the GSTM1 and GSTT1-null genotypes compared with those with the GSTM1 and GSTT1- present genotypes. No synergistic effects of smoking or GST genotypes were observed.
CONCLUSIONS: Our results indicate no overall association between the GSTM1 and GSTT1 deletion polymorphisms and pancreatic cancer risk in the Japanese subjects in our study.

Panic N, Mastrostefano E, Leoncini E, et al.
Susceptibility to Helicobacter pylori infection: results of an epidemiological investigation among gastric cancer patients.
Mol Biol Rep. 2014; 41(6):3637-50 [PubMed] Related Publications
The aim of this study was to identify the clinical, demographic, lifestyle factors and selected genetic polymorphisms that affect the susceptibility towards Helicobacter pylori (H. pylori) infection in gastric cancer patients. Histological confirmed gastric adenocarcinoma cases that underwent curative gastrectomy between 2002 and 2012 were included. Gastric biopsy samples were obtained to determine the H. pylori status, and further cagA status and vacA m and s genotypes by polymerase chain reaction. Patients were interviewed with structured questionnaires, and blood samples were collected for EPHX1, GSTM1, GSTT1, IL1B, IL1-RN, MTHFR and p53 genotyping. Proportions were compared in univariate analysis, while the relation between putative risk factors and H. pylori status and genotype were measured using logistic regression analysis. One hundred forty-nine gastric cancer patients were included, of which 78.5% were H. pylori positive. Among positive patients 50% were cagA+, 72.5% vacA m1 and 80.7% vacA s1. The presence of cagA was less frequent among vacA m1 (p = 0.031) and vacA s1 (p = 0.052) subtypes. The presence of father history for any cancer was a significant risk factor for H. pylori infection [adjusted odds ratio (OR) = 8.18, 95% confidence interval (CI) 1.04-64.55]. EPHX1 exon 3 T > C (OR = 0.35, CI 95% 0.13-0.94), IL1B-511 T > C (OR = 0.38, CI 95% 0.15-0.97) and IL1-RN VNTR (OR = 0.19, CI 95% 0.06-0.58) polymorphisms were protective towards H. pylori infection in the univariate analysis. Wine consumption was associated with higher risk of carrying the H. pylori vacA m1 virulent subtype (p = 0.034). Lastly, cardiovascular diseases were less common among cagA positive subjects (p = 0.023). Father history of any cancer is a risk factor for H. pylori infection. Polymorphisms in IL1B-511, IL1-RN and EPHX1 exon 3 genes might be protective towards H. pylori infection.

Maurya SS, Anand G, Dhawan A, et al.
Polymorphisms in drug-metabolizing enzymes and risk to head and neck cancer: evidence for gene-gene and gene-environment interaction.
Environ Mol Mutagen. 2014; 55(2):134-44 [PubMed] Related Publications
A case-control study involving 750 cases with squamous-cell carcinoma of the head and neck (HNSCC) and an equal number of healthy controls was initiated to investigate the association of polymorphisms in the drug metabolizing genes cytochrome P450 1A1 (CYP1A1), CYP1B1, CYP2E1 and glutathione S-transferase M1 (GSTM1) with the risk of developing cancer. Attempts were also made to identify the role and nature of gene-gene and gene-environment interactions in modifying the susceptibility to HNSCC. Polymorphisms in drug metabolizing CYPs or GSTM1 showed modest associations with cancer risk. However, cases carrying haplotypes with variant alleles of both CYP1A1*2A and *2C or CYP1B1*2 and *3 or CYP2E1*5B and *6 were at significant risk of developing HNSCC. Likewise, cases carrying a combination of variant genotypes of CYPs and GSM1 (null) were at higher risk (up to 5-fold) of developing HNSCC. HNSCC risk also increased several-fold in cases carrying variant genotypes of CYPs who were regular tobacco smokers (8-18-fold), tobacco chewers (3-7-fold), or alcohol users (2-4-fold). Statistical analysis revealed a more than multiplicative interaction between combinations of the variant genotypes of CYPs and GSTM1 (null) and between variant genotypes and tobacco smoking or chewing or alcohol consumption, in both case-control and case-only designs. The data thus suggest that although polymorphisms in carcinogen-metabolizing CYPs may be a modest risk factor for developing HNSCC, gene-gene, and gene-environment interactions play a significant role in modifying the susceptibility to HNSCC.

Gataa I, Emile G, Loriot MA, et al.
Association between high antitumor activity of oxaliplatin and cyclophosphamide and constitutional GSTM1 homozygous deletion in an advanced ovarian cancer patient.
Chemotherapy. 2013; 59(4):290-3 [PubMed] Related Publications
BACKGROUND: Although the efficiency of oxaliplatin in patients with advanced ovarian cancer has been demonstrated, it is not commonly used. In cells, oxaliplatin is metabolized by the enzymes belonging to the glutathione-S-transferase (GST) family.
CASE: A 55-year-old woman with advanced ovarian cancer received 6 cycles of paclitaxel and carboplatin after debulking surgery. Six months later, she experienced a clinical recurrence. A second-line chemotherapy combining 500 mg/m² cyclophosphamide with 100 mg/m² oxaliplatin was initiated and maintained for 10 cycles. The patient thus experienced a second complete remission that lasted for 6 years. We found that she had deficient GSTM1 enzyme activity with homozygous deletion and normal GSTP1 and GSTT1 activities.
CONCLUSION: The association of a homozygous deletion of GSTM1 with hypersensitivity to oxaliplatin and cyclophosphamide combination chemotherapy has not been described to date in ovarian cancer. Further study of its potential interest to personalized second-line therapy in these patients is called for.

Procopciuc LM, Osian G
GSTM1-null genotype as a risk factor for sporadic colorectal cancer in a Romanian population. Association with the NAT2-rapid-acetylator phenotype and exposure to environmental factors.
Cancer Invest. 2014; 32(2):53-62 [PubMed] Related Publications
We evaluated the association between the presence of the GSTM1-null genotype and the combined presence of the GSTM1-null genotype/NAT2 rapid acetylator phenotype and the risk of developing sporadic colorectal cancer (CRC), as well as their interaction with environmental risk factors. One hundred and fifty patients with sporadic CRC and 162 controls were genotyped using PCR-RFLP analysis. For testing and quantification of the simple effect (main effect) and of the gene-gene and gene-environment interaction (modification effect), univariate and multivariate logistic regression was used. In the multiplicative model, from the genetic factors, GSTM1-null and NAT2*6B had a statistically significant influence on the risk for CRC, while from the environmental factors, smoking and diet had similar effects. The combination of GSTM1-null/NAT2 rapid acetylator phenotype/smoking behavior or GSTM1-null/NAT2 rapid acetylator phenotype/diet rich in fried red meat was not found to influence the sporadic CRC risk in Romanians, but the GSTM1-null genotype, NAT2 rapid acetylator phenotype influenced the sporadic CRC risk differently depending on the gender of the patient.

Masood N, Yasmin A, Kayani MA
Genetic variations and head and neck cancer risks.
Mol Biol Rep. 2014; 41(4):2667-70 [PubMed] Related Publications
Variations in CYP1A1, GSTM1, GSTT1 and GSTP1 in head and neck cancer have been frequently found in literature. But these studies give an overview of these genetic variations in different populations. The current mini review focus on the analysis of these genetic variations at DNA, mRNA and protein levels in the same study group. Eight publications were reviewed on the same study samples yielding results at DNA, mRNA and protein levels. At DNA level, CYP1A1 showed significantly higher mutations in head and neck cancer patients compared to controls at g.2842A>C and g.2842_2843insT. GSTM1 and GSTT1 showed deletion polymorphisms and heterozygous deletion confers protection against cancer. Mutations were also found in GSTP1 at g.2848A>T, g.2849G>A, g.1074delC and g.1466delC. mRNA and protein expressional analysis revealed underexpression of CYP1A1, loss or underexpression of GSTM1 and GSTT1 and overexpression of GSTP1. In addition an unusual intronic variant of GSTP1 mRNA was also found, retaining the intronic portion between exons. The current review gives a complete study overview regarding CYP1A1, GSTM1, GSTT1 and GSTP1 variations at DNA, mRNA and protein levels in head and neck cancer. The review is helpful in designing a new experiment or gene therapy for head and neck cancer patients.

Shen YH, Chen S, Peng YF, et al.
Quantitative assessment of the effect of glutathione S-transferase genes GSTM1 and GSTT1 on hepatocellular carcinoma risk.
Tumour Biol. 2014; 35(5):4007-15 [PubMed] Related Publications
Hepatocellular carcinoma (HCC) is one of the most serious health problems worldwide. As in many other diseases, environment and genetic factors are believed to be involved in the pathogenesis of HCC. Numerous epidemiologic investigations including case-control and cohort studies have suggested the association of glutathione S-transferase (GST) genetic polymorphisms and HCC risk. However, some studies have produced conflicting results. Therefore, we performed an updated meta-analysis to clarify this inconsistency and to establish a comprehensive picture of the association of the polymorphisms of GSTM1 and GSTT1 with HCC susceptibility. We searched PubMed, Embase, ISI Web of Science, and CNKI databases to identify eligible studies meeting the inclusion criteria up to August 30, 2013. Odds ratios (ORs) and 95% confidence intervals (CIs) were used to assess the strength of association. Finally, there were a total of 33 studies with 4,232 cases and 6,601 controls included in this meta-analysis. In the pooled analysis, significantly increased HCC risks were found for null genotype of GSTM1 (OR = 1.31, 95% CI = 1.07-1.61, P = 0.010, P heterogeneity < 10(-5)) and GSTT1 (OR = 1.47, 95% CI = 1.25-1.74, P < 10(-5), P heterogeneity < 10(-5)). Potential sources of heterogeneity were explored by subgroup analysis based on ethnicity, sample size, and source of control. Significant results were found among East Asians and Indians when stratified by ethnicity, while no evidence of significant associations was observed among Caucasian and African populations. In the gene-gene interaction analysis, a statistically significant increased risk for HCC was detected for individuals with combined deletion mutations in both genes compared to those with wild genotypes (OR = 1.88, 95% CI = 1.41-2.50, P < 10(-4), P heterogeneity = 0.004). The present meta-analysis demonstrated that the GSTM1 and GSTT1 null genotype may be associated with an increased risk of HCC and that individuals having the combination of both defective GST genotypes may be more susceptible to developing HCC.

Haholu A, Berber U, Karagöz B, et al.
Is there any association of glutathione S-transferase T1 (GSTT1) and glutathione S-transferase M1 (GSTM1) gene polymorphism with gastric cancers?
Pol J Pathol. 2013; 64(4):247-52 [PubMed] Related Publications
The glutathione S-transferases (GST) are enzymes catalyzing reactions including carcinogens. GSTT1 and GSTM1 genes are polymorphic in humans. The relations between polymorphism of some GST genes and cancer have been reported. In this study, we aimed to investigate the distribution of GSTT1 and GSTM1 polymorphisms in a group of gastric cancer patients. The study group consisted of 50 patients (21 females, 29 males) with gastric adenocarcinoma from the archives of the pathology department of a training hospital. Fifty-seven healthy control subjects were included in the study as a control group. DNA was extracted from peripheral venous blood of control subjects and from the paraffin blocks of cases. Genotyping of GSTT1 and GSTM1 genes was performed with duplex polymerase chain reaction. No differences in the frequencies of GSTM1 or GSTT1 null genotypes were observed between patients and healthy subjects (GSTM1: 52% vs. 43.85%, OR = 1.27, 95% CI: 0.55-2.96; GSTT1: 38.46% vs. 28.07%, OR = 0.72, 95% CI: 0.25-1.96). Moreover, simultaneous carriage of both genotypes was almost identical in both groups. GSTM1 or GSTT1 null genotypes were not different in diffuse or intestinal type gastric cancer. Our data suggest that the GSTM1 and GSTT1 polymorphisms are not associated with gastric cancer in a small group of the Turkish population.

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