GSTM1

Gene Summary

Gene:GSTM1; glutathione S-transferase mu 1
Aliases: MU, H-B, GST1, GTH4, GTM1, MU-1, GSTM1-1, GSTM1a-1a, GSTM1b-1b
Location:1p13.3
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:VEGA, OMIM, HGNC, Ensembl, GeneCard, Gene
Protein:glutathione S-transferase Mu 1
Source:NCBIAccessed: 09 March, 2017

Ontology:

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 (1992-2017)
Graph generated 09 March 2017 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 09 March, 2017 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 Publications265
Lung CancerGSTM1 and Lung Cancer View Publications259
Colorectal CancerGSTM1 and Colorectal Cancer View Publications151
Breast CancerGSTM1 and Breast Cancer View Publications152
Bladder CancerGSTM1 and Bladder Cancer View Publications134
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 Publications87
Prostate CancerGSTM1 and Prostate Cancer View Publications77
Oral Cavity CancerGSTM1 and Oral Cavity Cancer View Publications80
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 Publications25
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)

Negovan A, Iancu M, Moldovan V, et al.
The Interaction between GSTT1, GSTM1, and GSTP1 Ile105Val Gene Polymorphisms and Environmental Risk Factors in Premalignant Gastric Lesions Risk.
Biomed Res Int. 2017; 2017:7365080 [PubMed] Free Access to Full Article Related Publications
The study investigated the possible influence of GSTM1, GSTT1, and GSTP1 gene polymorphisms as predisposing factors for premalignant gastric lesions as well as their interaction with H. pylori infection, gastrotoxic drugs, smoking, and alcohol consumption. In this study, 270 patients with a complet set of gastric biopsies and successfully genotyped were finally included. The GSTM1 gene polymorphism had significant contribution in mild/severe endoscopic lesions (p = 0.01) as well as in premalignant lesions (p = 0.01). The GSTM1 null genotype increased the risk for mucosal defects in H. pylori-negative patients (OR = 2.27, 95% CI: 1.20-4.37) and the risk for premalignant lesions in patients with no alcohol consumption (OR = 2.13, 95% CI: 1.19-3.83). The GSTT1 deleted polymorphism did not significantly increase the risk for premalignant lesions in the absence of gastrotoxic drugs (OR = 1.82, 95% CI: 0.72-4.74). The combined GSTT1T1 and GSTM1 null polymorphisms were borderline correlated with an increased risk for premalignant lesions (OR = 1.72, 95% CI: 1.00-2.97). The wild-type GSTP1 Ile/Ile genotype versus the variant genotypes Ile/Val + Val/Val was significantly associated with a decreased risk of gastric atrophy/intestinal metaplasia (OR = 0.60, 95% CI: 0.37-0.98). In conclusion, the GSTM1 and GSTT1 null genotypes increased the risk for premalignant and endoscopic gastric lesions, modulated by H. pylori, alcohol, or gastrotoxic drug consumption, while the presence of the GSTP1Val allele seemed to reduce the risk for premalignant lesions.

Drozd E, Krzysztoń-Russjan J, Marczewska J, et al.
Up-regulation of glutathione-related genes, enzyme activities and transport proteins in human cervical cancer cells treated with doxorubicin.
Biomed Pharmacother. 2016; 83:397-406 [PubMed] Related Publications
Doxorubicin (DOX), one of the most effective anticancer drugs, acts in a variety of ways including DNA damage, enzyme inhibition and generation of reactive oxygen species. Glutathione (GSH) and glutathione-related enzymes including: glutathione peroxidase (GPX), glutathione reductase (GSR) and glutathione S-transferases (GST) may play a role in adaptive detoxification processes in response to the oxidative stress, thus contributing to drug resistance phenotype. In this study, we investigated effects of DOX treatment on expression and activity of GSH-related enzymes and multidrug resistance-associated proteins in cultured human cervical cancer cells displaying different resistance against this drug (HeLa and KB-V1). Determination of expression level of genes encoding GST isoforms and MRP proteins (GCS, GPX, GSR, GSTA1-3, GSTM1, GSTP1, ABCC1-3, MGST1-3) was performed using StellARray™ Technology. Enzymatic activities of GPX and GSR were measured using biochemical methods. Expression of MRP1 was examined by immunofluorescence microscopy. This study showed that native expression levels of GSTM1 and GSTA3 were markedly higher in KB-V1 cells (2000-fold and 200-fold) compared to HeLa cells. Resistant cells have also shown significantly elevated expression of GSTA1 and GSTA2 genes (200-fold and 50-fold) as a result of DOX treatment. In HeLa cells, exposure to DOX increased expression of all genes: GSTM1 (7-fold) and GSTA1-3 (550-fold, 150-fold and 300-fold). Exposure to DOX led to the slight increase of GCS expression as well as GPX activity in KB-V1 cells, while in HeLa cells it did not. Expression of ABCC1 (MRP1) was not increased in any of the tested cell lines. Our results indicate that expression of GSTM1 and GSTA1-3 genes is up-regulated by DOX treatment and suggest that activity of these genes may be associated with drug resistance of the tested cells. At the same time, involvement of MRP1 in DOX resistance in the given experimental conditions is unlikely.

Jia W, Sun JY, Jia KY, Liu XC
Role of GSTM1, GSTT1, and GSTP1 IIe105Val gene polymorphisms in the response to chemotherapy and overall survival of advanced non-small cell lung cancer.
Genet Mol Res. 2016; 15(3) [PubMed] Related Publications
We evaluated the association between GSTM1, GSTT1, and GSTP1 IIe105Val gene polymorphisms and treatment outcomes of advanced non-small cell lung carcinoma. Between January 2010 and December 2012, a total of 244 patients with non-small cell lung carcinoma were recruited from Yiwu Central Hospital. The GSTM1, GSTT1, and GSTP1 IIe105Val gene polymorphisms were analyzed by polymerase chain reaction-restriction fragment length polymorphism and the results were statistically analyzed. Conditional regression analysis, showed that individuals carrying the null GSTM1 were associated with an increased risk of response to chemotherapy when compared to the present GSTM1 (odds ratio = 1.88, 95% confidence interval (CI) = 1.01-3.47). Moreover, the GG genotype of GSTP1 IIe105Val was associated with a better response to chemotherapy compared to the AA genotype (odds ratio = 2.77, 95%CI = 1.14-6.64). The null GSTM1 genotype was associated with a lower risk of death from all causes when compared with the present GSTM1 genotype (hazard ratio = 2.16, 95%CI = 1.10-4.38). Moreover, the GG genotype of GSTP1 IIe105Val was correlated with a reduced risk of death from all causes compared with the AA genotype (hazard ratio = 2.94, 95%CI = 1.11-8.68). In conclusion, we found that the null GSTM1 and the GG genotype of GSTP1 IIe105Val were correlated with a good response to chemotherapy and improved overall survival of advanced non-small cell lung carcinoma patients.

Malik SS, Kazmi Z, Fatima I, et al.
Genetic Polymorphism of GSTM1 and GSTT1 and Risk of Prostatic Carcinoma - a Meta-analysis of 7,281 Prostate Cancer Cases and 9,082 Healthy Controls.
Asian Pac J Cancer Prev. 2016; 17(5):2629-35 [PubMed] Related Publications
Genetic polymorphisms constitute one of the reasons behind the racial variation in prostate cancer occurrence. Published studies regarding genetic associations of glutathione S-transferase mu 1 (GSTM1) and glutathione S-transferase theta 1 (GSTT1) null deletion polymorphisms with prostatic carcinoma have generated inconsistent results among different populations. To date, even a single meta-analysis is not available representing the association of these genes with prostate cancer in different ethnic groups. Therefore, the aim of the current study was to provide a clear picture of GSTM1 and GSTT1 null deletion and risk of prostate cancer among different ethnic groups (i.e. Asians, Europeans, Americans, Africans and Eurasians). A systematic search was performed with the help of various search engines to find out the all the recent studies (2004 to 2015) evaluating the role of GSTM1 and GSTT1 deletion in prostate cancer development. Odds ratios (ORs) with 95% confidence interval (CI) of a total of 34 studies with 7,281 cases and 9,082 controls was analyzed using STATA and MedCalc software. Overall, GSTM1 deletion (OR 3.67; CI 1.39-9.85; P= 0.001) was strongly associated with prostatic cancer. In the sub group analysis GSTM1 null deletion was also significantly associated with prostate cancer among Asians (OR 4.84; CI 1.08-21.5; P= 0.03), Eurasians (OR 17.69; CI 9.87-31.70; <0.001) and Americans (OR 0.11; CI 0.01-1.06; P= 0.05). No association was observed among Europeans (P=0.42) and Africans (P= 0.40). As a whole GSTT1 null deletion (OR 0.85; CI 0.28-2.58; P= 0.77) did not show anyt significant association with prostate cancer risk among different populations. When the data were stratified into different groups, however, Africans demonstrated a significant association of GSTT1 null deletion (OR 1.95; CI 1.57-2.39; <0.001) with prostate cancer, whereas no association was found among Asians (P= 0.90), Americans (P= 0.50), Europeans (P= 0.89) and Eurasians (P= 1.0). In conclusion, both GSTM1 and GSTT1 may contribute to prostate cancer development but GSTM1 may prove to be a stronger candidate risk factor.

Peddireddy V, Badabagni SP, Gundimeda SD, et al.
Association of CYP1A1, GSTM1 and GSTT1 gene polymorphisms with risk of non-small cell lung cancer in Andhra Pradesh region of South India.
Eur J Med Res. 2016; 21:17 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: Lung cancer is one of the most preventable causes of death globally both in developed and developing countries. Although it is well established that smokers develop lung cancer, there are some smokers who are free from the disease risk. The predisposition to lung cancer is attributed to genetic polymorphisms in xenobiotic metabolizing genes. Reports on assessment of xenobiotic metabolizing genes like Cytochrome P 450 1A1 (CYP1A1), Glutathione -S -transferase M1 (GSTM1) and T1 (GSTT1) polymorphisms from India are meagre, and reports from Andhra Pradesh are lacking.
METHODS AND RESULTS: Assessment of polymorphisms in CYP1A1, GSTM1 and GSTT1 in NSCLC patients and healthy individuals specific to population of Andhra Pradesh, a South Indian state was attempted by multiplex PCR and RFLP, and this is the first study which tried to correlate oxidative stress with the polymorphisms in xenobiotic metabolizing genes. Results showed that CYP1A1 m1 'CC' genotype was significantly associated with lung cancer susceptibility with a 2.3-fold risk, CYP1A1 m2 'AG' gene polymorphisms with 8.8-fold risk and GSTT1 (-/-) genotype demonstrated a twofold risk of disease susceptibility.
CONCLUSIONS: A combined role of genetic polymorphisms and smoking status can be attributed for the cause of lung cancer. Further, the association between oxidative stress and genetic polymorphisms showed a correlation between GSTT1 and super oxide dismutase activity; CYP1A1 m1, m2 and GSTT1 with glutathione peroxidase activity; CYP1A1 m1 and GSTM1 with melondialdehyde levels; and CYP1A1 m1 and GSTT1 with 8-oxo-7,8-dihydro-2'-deoxyguanosine. A higher risk of lung cancer seems to be associated with combined gene polymorphisms of phase I and phase II enzymes than that ascribed to single gene polymorphism.

Ghatak S, Yadav RP, Lalrohlui F, et al.
Xenobiotic Pathway Gene Polymorphisms Associated with Gastric Cancer in High Risk Mizo-Mongoloid Population, Northeast India.
Helicobacter. 2016; 21(6):523-535 [PubMed] Related Publications
BACKGROUND: The aim of this study was to evaluate the risk of gastric cancer associated with individual or combined glutathione S-transferases (GSTs) polymorphism and their interaction with environmental factors.
MATERIALS AND METHODS: Genotyping by PCR was carried out for 80 cases and controls each for GSTM1, GSTT1, and GSTP1 polymorphism and mapped for gene-environment association studies. The samples were subjected to pathogen detection and GSTP1 expression for analyzing their association with different genotypes. Logistic regression analyses were conducted to compute the influence of both genetic and environmental factors for gastric cancer. MDR analysis was performed to assess the risk of gastric cancer by studying the gene-gene and gene-environment effect on the basis of GST genotyping and GSTP1 gene expression.
RESULTS: Infection with Helicobacter pylori and CagA+ strains was more frequent in patients with GSTM1/T1 null genotype. Intake of high fermented fat and smoked meat was found to be significantly associated with gastric cancer. The G/G, A/G (rs1695), and T/T (rs1138272) were found to be significantly associated with low expression of GSTP1 gene in cancer tissue.
CONCLUSION: Presence of H. pylori with CagA genotype showed significant individual effect with GSTT1 polymorphism as well as strong synergistic effect in gastric cancer risk. Majority of the gastric cancer samples showed significant negative expression in G/G, A/G (rs1695), and T/T (rs1138272) genotypes. This study shows that GST gene polymorphism was significantly relevant for determining the individual susceptibility to gastric cancer.

Nasr AS, Sami RM, Ibrahim NY, Darwish DO
Glutathione S transferase (GSTP 1, GSTM 1, and GSTT 1) gene polymorphisms in Egyptian patients with acute myeloid leukemia.
Indian J Cancer. 2015 Oct-Dec; 52(4):490-5 [PubMed] Related Publications
BACKGROUND: The super family of glutathione S-transferases (GSTs) is composed of multiple isoenzymes with significant evidence of functional polymorphic variation. GSTs detoxify potentially mutagenic and toxic DNA-reactive electrophiles, including metabolites of several chemotherapeutic agents, some of which are suspected human carcinogens. Polymorphisms within the phase II metabolizer enzymes GST T1, GST M1, and GST P1 affect the body's ability to detoxify a range of potential leukemogens encountered in the environment.
AIM OF WORK: To address how differences in the human GST isoenzyme expression patterns influence cancer susceptibility, prognosis, and treatment.
PATIENTS AND METHODS: A total of 50 patients with acute myeloid leukemia (AML), as well as 50 age and sex matched apparently healthy volunteers were genotyped for GSTP 1, GSTM 1, and GSTT 1 gene polymorphisms using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and conventional polymerase chain reaction (PCR), respectively.
RESULTS: For GSTP1 313 A → G (GSTP1 Ile105Val) polymorphism, It was found that the wild genotype (AA) was significantly higher among control subjects (P value = 0.0277), while the frequency of heteromutant genotype (AG) and mutant G allele (AG + GG) was significantly higher among patients (P value = 0.0402, P value = 0.0277, respectively). For GSTM1 and GSTT1gene, we found statistically significantly higher frequency among patients regarding homozygous gene deletion (P value = 0.0005).
CONCLUSION: We demonstrated that GSTM1 null or GSTT1 null genotypes may be considered independent risk factors for AML with no impact on prognosis and GSTP1 * 105 genotype is a prognostic factor, adding independent information to the routine laboratory parameters and cytogenetic and molecular alterations of the tumor cells.

Khabaz MN, Nedjadi T, Gari MA, et al.
GSTM1 gene polymorphism and the risk of colorectal cancer in a Saudi Arabian population.
Genet Mol Res. 2016; 15(1) [PubMed] Related Publications
The enzyme glutathione S-transferase Mu 1 (GSTM1) is encoded by the GSTM1 gene. Polymorphisms in GSTM1 affect the detoxifying function of the enzyme variants. This forms the basis of the debate about the impact of the GSTM1 null/present genotype on colorectal carcinoma risk. We tested the potential influence of GSTM1 polymorphisms on the development of colorectal cancer. DNA extracted from 83 samples taken from patients that were previously diagnosed as having colorectal carcinoma and from 35 control subjects who did not have colorectal carcinoma were amplified. GSTM1 genotypes were determined by DNA sequencing. The current study revealed that the majority (69/83, 83%) of colorectal cancer cases harbored the null genotype (GSTM1*0/*0), and the remaining 14 (17%) cases harbored either the GSTM1wt/wt or the GSTM1wt/*0 genotype. In contrast, among the control cases, 23 (65%) had the null genotype (GSTM1*0/*0) and 12 (35%) had either the GSTM1wt/wt or the GSTM1wt/*0 genotype. The current report emphasizes the impact of the GSTM1 null genotype on the increased risk of colorectal carcinoma in Saudi Arabia.

Antonova O, Toncheva D, Grigorov E
Bladder cancer risk from the perspective of genetic polymorphisms in the carcinogen metabolizing enzymes.
J BUON. 2015 Nov-Dec; 20(6):1397-406 [PubMed] Related Publications
Urinary bladder cancer is a socially significant healthcare problem. A diverse array of aromatic and heterocyclic amines, derived from the chemical and transport industry, diet, and cigarette smoke are considered carcinogens for the bladder. To exert their carcinogenic effect and to initiate the carcinogenic response, the arylamines require a metabolic activation by the host enzymes to chemically reactive compounds. The aim of this article was to review the latest and basic research developments on the role of the polymorphisms in the carcinogen metabolizing enzymes N-acetyltransferase (NAT), Glutathione S-transferases (GST), and Soluble sulfotransferases (SULT), with emphasis on the susceptibility to urinary bladder cancer. A PubMed search was conducted to identify original and review articles containing information about these polymophic variants in different populations and according to their prevalence in bladder cancer patients. We noticed that some genotypes were found to be predisposing and some protective for bladder cancer development. The NAT2 slow genotype, together with GSTM1 null genotype facilitated the development of bladder cancer in almost all ethnic groups. The 213His allele of the SULT1A1 gene which is associated with lower enzyme activity and decreased mutagen activation was reported to protect from bladder cancer in almost all studies.

Bănescu C, Iancu M, Trifa AP, et al.
From Six Gene Polymorphisms of the Antioxidant System, Only GPX Pro198Leu and GSTP1 Ile105Val Modulate the Risk of Acute Myeloid Leukemia.
Oxid Med Cell Longev. 2016; 2016:2536705 [PubMed] Free Access to Full Article Related Publications
Oxidative stress might contribute to the occurrence of cancers, including the hematological ones. Various genetic polymorphisms were shown to increase the quantity of reactive oxygen species, a phenomenon that is able to induce mutations and thus promote cancers. The purpose of the study was to evaluate the association between CAT C262T, GPX1 Pro198Leu, MnSOD Ala16Val, GSTM1, GSTT1, and GSTP1 Ile105Val gene polymorphisms and acute myeloid leukemia risk, in a case-control study comprising 102 patients and 303 controls. No association was observed between AML and variant genotypes of CAT, MnSOD, GSTM1, and GSTT1 polymorphisms. Our data revealed a statistically significant difference regarding the frequencies of GPX1 Pro198Leu and GSTP1 Ile105Val variant genotypes between AML patients and controls (p < 0.001). Our results showed no association in the distribution of any of the CAT C262T, GPX1 Pro198Leu, GSTM1, GSTT1, and GSTP1 polymorphisms regarding age, gender, FAB subtype, cytogenetic risk groups, FLT3 and DNMT3 gene mutations, and overall survival. Our data suggests that the presence of variant allele and genotype of GPX1 Pro198Leu and GSTP1 Ile105Val gene polymorphisms may modulate the risk of developing AML.

Mostafavi SS, Ebrahimi A, Sadat SM, et al.
Impact of null genotypes of GSTT1 and GSTM1 with uterine leiomyoma risk in Iranian population.
J Obstet Gynaecol Res. 2016; 42(4):434-9 [PubMed] Related Publications
AIM: Few studies have investigated the role of the GSTM1 and GSTT1 genes in uterine leiomyoma. Therefore, in the current study the distribution of these genotypes in Iranian women and susceptibility to uterine leiomyoma was investigated.
METHODS: Blood samples of 50 patients with uterine leiomyoma and 50 healthy individual controls were collected in this cross-sectional study. Genomic DNA was extracted, and subsequently GSTM1 and GSTT1 null genotypes were detected by the Gap-polymerase chain reaction method.
RESULTS: A total of 42% of patients appeared to lack GSTM1 enzyme activity due to the presence of an extended deletion (GSTM1 0/0 genotype), compared with 18% in a control group (odds ratio [OR], 3.56; 95% confidence interval [CI], 1.35-9.37; P < 0.010). In addition, the prevalence of the GSTT1 null genotype in patients was higher than that in the control group (42% to 14%, P < 0.009). Also, it was shown that individuals with both null genotypes (-/-) had a 19.23-fold higher risk of developing the disease in comparison to people who showed both present genotypes (+/+). (P = 0.007; 95%CI, 2.20-167.41). Besides, it was observed that at least one null genotype increases the risk of myoma to 2.6 compared to the both present genotype (P-value < 0.03, 95%CI, 1.05-6.82).
CONCLUSION: To our knowledge, this is first significant correlation between risk of uterine leiomyoma and null GSTM1 and GSTT1 genotypes among Iranian patients. Our data support the involvement of GSTM1 and GSTT1 in uterine leiomyoma liability, and especially its role as a genetic factor in the occurrence of this disease.

Xie YQ, Chen JM, Liu Y
Interaction of the CYP1A1 gene polymorphism and smoking in non-small cell lung cancer susceptibility.
Genet Mol Res. 2016; 14(4):19411-7 [PubMed] Related Publications
Many studies have shown that genetic factors, environmental factors, and bad living habits, especially smoking, are risk factors for lung cancer. However, not all smokers develop lung cancer, which may be related to different genetic backgrounds. Currently, most research has investigated the GSTM1, XRCC1, XRCC3, CYP2D6, and C188T genes. Little research has been done on the cytochrome P450 (CYP) 1A1 gene, and results have varied. In addition, no results have been reported on the interactive effects of smoking and the CYP1A1 gene on lung cancer development. We used polymerase chain reaction restriction fragment length polymorphism to detect the CYP1A1 genotype, and investigate the effects of the CYP1A1 gene deletion and smoking alone, and in combination, on non-small cell lung cancer susceptibility. We enrolled 150 non-small cell lung cancer patients and 150 healthy control subjects. Subjects' smoking habits and CYP1A1 gene polymorphism were analyzed to investigate their role in the occurrence of lung cancer. The CYP1A1 gene deletion was found in 73.3% of non-small cell lung cancer patients and 20.0% of healthy subjects. The OR value was 2.28 (P < 0.05). Among smoking subjects, 77.8% exhibited non-small cell lung cancer, significantly higher than the 27.3% in non-smokers (P < 0.05). The OR value for the interaction of smoking and CYP1A1 gene deletion was 5.60, larger than the product of their individual OR values. The CYP1A1 gene deletion is a lung cancer risk factor, and interacts with smoking in non-small cell lung cancer development.

Zeng M, Lv Y, Wang HF, et al.
Correlation of CYP1A1 and GSTM1 gene polymorphisms and environmental factors to familial aggregation of esophageal cancer among the Kazakh ethnic group in Xinjiang.
Genet Mol Res. 2015; 14(4):19102-9 [PubMed] Related Publications
This study aimed to investigate the correlation of CYP1A1 and GSTM1 gene polymorphisms and environmental factors to familial aggregation of esophageal cancer (EC) among the Kazakh ethnic group in Xinjiang. CYP1A1 and GSTM1 gene polymorphisms were detected using peripheral blood from 86 subjects belonging to families with EC and 82 control subjects. Additionally, a questionnaire survey was conducted to ascertain environmental risk factors. Combined effects of CYP1A1 and GSTM1 gene polymorphisms and environmental factors in familial aggregation of EC were evaluated. Distribution frequencies of CYP1A1 MspI and GSTM1 genotypes between EC and control families showed significant differences (P = 0.002, P = 0.001). Contribution of interaction between CYP1A1 MspI mutant and GSTM1 deletion polymorphisms to familial aggregation of EC was significant, with OR = 3.571 (95%CI = 1.738-3.346). Logistic multivariate analysis indicated that familial aggregation of EC is correlated with 3 factors: drinking water, intake of fresh vegetables and fruits, and CYP1A1 MspI polymorphism (P = 0.005, P = 0.013, and P = 0.001). Sufficient intake of fresh vegetables and fruits (OR = 0.278, 95%CI = 0.137-0.551) protected against familial aggregation of EC, while drinking water (OR = 3.468, 95%CI = 1.562-6.551) and CYP1A1 MspI polymorphism (OR = 2.732, 95%CI = 1.741-3.886) were the risk factors. In conclusion, CYP1A1 and GSTM1 gene polymorphisms affect familial aggregation of EC among the Kazakh ethnic group in Xinjiang. River water intake and CYP1A1 MspI polymorphism were risk factors that likely contributed to high incidence of EC among families.

Rodrigues DA, Costa IR, Martins JV, et al.
Polymorphisms of GSTM1, GSTT1, and p53 in Goiânia, Goiás.
Genet Mol Res. 2015; 14(4):17358-65 [PubMed] Related Publications
Genetic polymorphisms are defined as changes within the DNA sequences of genes that have frequencies in the population higher than 1%. The glutathione S-transferases play an important role in the cellular detoxification systems involved in oxidative stress that can lead to accumulation of reactive oxygen species. Epidemiological studies have suggested that individuals with homozygous deletion of glutathione S-transferase mu 1 (GSTM1) and glutathione S-transferase theta 1 (GSTT1) are at higher risk of developing several types of neoplasias. The p53 protein is highly expressed in tumors and transformed cells, and the p53 is a classical tumor suppressor gene involved in regulating cell growth and development. In this study, we investigated the prevalence of polymorphisms in the p53, GSTM1, and GSTT1 genes in a population from Goiânia. We evaluated the polymorphisms of these genes in peripheral blood samples. The null or present polymorphism of GSTM1 and GSTT1 genes and Arg/Pro of the p53 gene were analyzed. Our results revealed a higher frequency of the GSTM1-null polymorphism (72.4%) than the GSTM1-present genotype (27.6%). For GSTT1, we observed higher frequency for the null genotype (65.5%) compared to the present genotype (34.5%). Analysis of p53 gene polymorphisms showed a higher frequency for the genotype Arg/Pro (66%) and a lower frequency for the Arg/Arg (23%) and Pro/Pro (11%) genotypes. It is essential to understand polymorphism frequencies in different populations and to evaluate the role of genetic polymorphisms and their effects on health.

Ghosh S, Ghosh S, Bankura B, et al.
Association of DNA repair and xenobiotic pathway gene polymorphisms with genetic susceptibility to gastric cancer patients in West Bengal, India.
Tumour Biol. 2016; 37(7):9139-49 [PubMed] Related Publications
Gastric cancer is one of the most common malignancies in India. DNA repair gene or xenobiotic pathway gene polymorphisms have recently been shown to affect individual susceptibility to gastric cancer. Here, the possible interaction between common polymorphisms in X-ray repair cross complementing group I (XRCC1) gene and glutathione S-transferase (GST) genes (GSTM1, GSTT1 and GSTP1), smoking and alcohol consumption and overall survival in gastric cancer patients were evaluated. In this population-based case control study, 70 gastric cancer patients and 82 healthy controls were enrolled. The epidemiological data were collected by a standard questionnaire, and blood samples were collected from each individual. XRCC1 Arg194Trp, Arg280His and Arg399Gln polymorphisms were determined by polymerase chain reaction and direct DNA sequencing. GSTM1 and GSTT1 null polymorphisms and GSTP1 Ile105Val polymorphism were identified by multiplex polymerase chain reaction and restriction fragment length polymorphism (RFLP), respectively. The risk of gastric cancer was significantly elevated in individuals with XRCC1 Arg/Gln +Gln/Gln (p = 0.031; odds ratio = 2.32; 95 % confidence interval (CI) 1.07-5.06) and GSTP1 Val/Val genotype (p = 0.009; odds ratio = 8.64; 95 % CI 1.84-40.55). An elevated risk for GC was observed in smokers and alcohol consumers carrying GSTP1 Ile/Val +Val/Val genotype (p = 0.041; odds ratio = 3.71; 95 % CI 0.98-14.12; p = 0.002; odds ratio = 12.31; 95 % CI 1.71-88.59). These findings suggest that XRCC1 rs25487 and GSTP1 rs1695 can be considered as a risk factor associated with gastric cancer and might be used as a molecular marker for evaluating the susceptibility of the disease.

Wu G, Jiang B, Liu X, et al.
Association of GSTs gene polymorphisms with treatment outcome of advanced non-small cell lung cancer patients with cisplatin-based chemotherapy.
Int J Clin Exp Pathol. 2015; 8(10):13346-52 [PubMed] Free Access to Full Article Related Publications
We evaluated the association of GSTM1 null/present, GSTT1 null/present, and GSTP1 IIe105Val polymorphisms with the clinical response to chemotherapy and treatment outcome of NSCLC. Between October 2009 and October 2012, a total of 282 patients with advanced NSCLC were enrolled into our study, and they were followed up until October 2014. The genotypes of GSTM1, GSTT1, and GSTP1 IIe105Val were performed by polymerase chain reaction (PCR) coupled with restriction fragment length polymorphism (RFLP). By logistic regression analysis, our study found that the Val/Val genotype of GSTP1 IIe105Val was associated with more CR+PR response to chemotherapy when compared with the IIe/IIe genotype, and the OR (95% CI) was 2.18 (1.16-4.12). By multivariate Cox proportional hazards regression analysis, we found the Val/Val genotype of GSTP1 was correlated with lower risk of death in advanced NSCLC (HR, 0.48; 95% CI, 0.25-0.93). However, no association was found between GSTT1 and GSTM1 polymorphisms and response to chemotherapy and overall survival of advanced NSCLC. Moreover, the IIe/Val + Val/Val genotypes of GSTP1 were associated with lower risk of death in never smokers, and the adjusted HR (95% CI) was 0.34 (0.12-0.93). In conclusion, we found that the GSTP1 polymorphism was correlated with better response to chemotherapy and lower risk of death in advanced NSCLC patients.

Zmorzyński S, Świderska-Kołacz G, Koczkodaj D, Filip AA
Significance of Polymorphisms and Expression of Enzyme-Encoding Genes Related to Glutathione in Hematopoietic Cancers and Solid Tumors.
Biomed Res Int. 2015; 2015:853573 [PubMed] Free Access to Full Article Related Publications
Antioxidant compounds such as glutathione and its enzymes have become the focus of attention of medical sciences. Glutathione, a specific tripeptide, is involved in many intercellular processes. The glutathione concentration is determined by the number of GAG repeats in gamma-glutamylcysteine synthetase. GAG polymorphisms are associated with an increased risk of schizophrenia, berylliosis, diabetes, lung cancer, and nasopharyngeal tumors. Cancer cells with high glutathione concentration are resistant to chemotherapy treatment. The oxidized form of glutathione is formed by glutathione peroxidases (GPXs). The changes in activity of GPX1, GPX2, and GPX3 isoforms may be associated with the development of cancers, for example, prostate cancer or even colon cancer. Detoxification of glutathione conjugates is possible due to activity of glutathione S-transferases (GSTs). Polymorphisms in GSTM1, GSTP1, and GSTO1 enzymes increase the risk of developing breast cancer and hepatocellular carcinoma. Gamma-glutamyl transpeptidases (GGTs) are responsible for glutathione degradation. Increased activity of GGT correlates with adverse prognosis in patients with breast cancer. Studies on genes encoding glutathione enzymes are continued in order to determine the correlation between DNA polymorphisms in cancer patients.

Li L, Li JG, Liu CY, Ding YJ
Effect of CYP1A1 and GSTM1 genetic polymorphisms on bone tumor susceptibility.
Genet Mol Res. 2015; 14(4):16600-7 [PubMed] Related Publications
Tumor gene polymorphisms are often associated with individual susceptibility to genetic diseases. Cytochrome P4501A1 (CYP1A1) and glutathione S-transferase mu 1 (GSTM1) gene polymorphisms are closely related to the susceptibility of the body to chemical carcinogens in the environment. Therefore, we explored the relationship between CYP1A1 and GSTM1 gene polymorphisms and susceptibility to bone tumors. Multiplex-polymerase chain reaction (PCR), allelic-specific PCR, and PCR-restriction fragment length polymorphism techniques were used to analyze CYP1A1 and GSTM1 gene polymorphisms in 52 bone tumor patients and 100 healthy subjects. The allelic variation frequency of the CYP1A1 gene at exon 7 (Ile 462 Val) in bone tumor patients was 0.462, which was significantly higher than that in the normal controls (0.223). The frequency of the absence of the GSTM1 homozygous genotype in the patients (0.65) was also markedly higher than that in the control group (0.41). Subjects with CYP1A1 Val/Val homozygous mutations and absence of the GSTM1 homozygous genotype were at markedly increased risk of developing bone tumors [ORs 4.15 (95%CI: 1.268-13.30) and 2.35 (95%CI: 1.15-4.85), respectively]. The OR for the combined effect of the CYP1A1 and GSTM1 gene polymorphisms was 8.55 (95%CI: 1.75-41.50). CYP1A1 and GSTM1 polymorphisms are genetic risk factors in patients with bone tumors, and the allelic variation of these genes increases the risk of bone tumor occurrence.

Huang W, Shi H, Hou Q, et al.
GSTM1 and GSTT1 polymorphisms contribute to renal cell carcinoma risk: evidence from an updated meta-analysis.
Sci Rep. 2015; 5:17971 [PubMed] Free Access to Full Article Related Publications
Emerging evidences suggest that GSTM1 and GSTT1 are involved in the detoxification of carcinogens, and polymorphisms in this gene that result in a loss of enzyme activity may increase the risk of renal cell carcinoma (RCC). Thus, to evaluate the association of GSTM1 and GSTT1 polymorphisms and RCC, we performed an updated meta-analysis of 10 case-control studies by RevMan 5.2, and the publication bias was tested using STATA 11.0. The meta-analysis showed that the single locus GSTM1 and GSTT1 polymorphisms were not significantly associated with a risk of RCC in a recessive model. However, that wild-type genotype versus the dual null genotype of GSTM1-GSTT1 showed a positive association with RCC risk (OR = 0.70; 95% CI = 0.51-0.98; P = 0.04). In another analysis of subjects exposed to pesticides, we found that the GSTM1 wild-type genotype was associated with increased RCC risk in Europeans (OR = 2.72; 95% CI = 1.54-4.82; P = 0.0006). We also identified an association between the GSTT1 wild-type and lower RCC TNM staging (I + II versus III + IV: OR = 1.88; 95% CI = 1.09-3.26; P = 0.02). This meta-analysis suggests that there may be a relationship between the GSTM1 and GSTT1 wild-type genotype and RCC.

Lacombe L, Fradet V, Lévesque É, et al.
Phase II Drug-Metabolizing Polymorphisms and Smoking Predict Recurrence of Non-Muscle-Invasive Bladder Cancer: A Gene-Smoking Interaction.
Cancer Prev Res (Phila). 2016; 9(2):189-95 [PubMed] Related Publications
Cigarette smoking is the most important known risk factor for urinary bladder cancer. Selected arylamines in cigarette smoke are recognized human bladder carcinogens and undergo biotransformation through several detoxification pathways, such as the glutathione S-transferases (GST), and uridine-diphospho-glucuronosyltransferases (UGT) pathways. GSTM1 deletion status and UGT1A1*28 rs8175347 genotypes were assessed in 189 non-muscle-invasive bladder cancers (NMIBC) patients with pTa (77.2%) and pT1 (22.8%) tumors and a mean follow-up of 5.6 years, to investigate whether two common functional polymorphisms in GSTM1 and UGT1A1 genes and smoking history are associated with recurrence-free survival of patients with NMIBC. Most patients were current (48.7%) or previous (35.4%) cigarette smokers and 15.9% never smoked. Tumor recurrence occurred in 65.1% of patients, at a median time of 12.9 months. Upon multivariate analysis, previous and current smokers approximately tripled their risk of recurrences [HR = 2.76; 95% confidence interval (CI), 1.03-7.40 and HR = 2.93; 95% CI, 1.08-7.94, respectively]. When adjusted for age, smoking status, stage, grade, gender, and presence of carcinoma in situ, carriers of GSTM1 (+/- and -/-) and UGT1A1*28/*28 alleles were significantly at risk of NMIBC recurrence (HR = 10.05; 95% CI, 1.35-75.1 and HR = 1.91; 95% CI, 1.01-3.62, respectively). Compared with nonsmokers with UGT1A1*1/*1 and *1/*28 genotypes, previous and current smokers homozygous for the UGT1A1*28 allele demonstrated a risk of recurrence of 4.95 (95% CI, 1.02-24.0) and 5.32 (95% CI, 2.07-13.7), respectively. This study establishes a connection between GSTM1, UGT1A1, and tobacco exposure as prognostic markers of NMIBC recurrence in bladder cancer patients. These findings warrant validation in larger cohorts.

Abbas M, Kushwaha VS, Srivastava K, Banerjee M
Glutathione S-Transferase Gene Polymorphisms and Treatment Outcome in Cervical Cancer Patients under Concomitant Chemoradiation.
PLoS One. 2015; 10(11):e0142501 [PubMed] Free Access to Full Article Related Publications
PURPOSE: Cisplatin based concomitant chemoradiation (CRT) is the standard treatment for locally advanced cervical cancer (CC). Glutathione S-transferase (GST), a phase II antioxidant enzyme is induced by oxidative stress generated by drugs and reactive oxidants. The present study was undertaken to evaluate the association of GSTM1, T1 and P1 polymorphisms with the outcome of CRT treatment in CC patients.
METHODS: A total of 227 cervical cancer patients with stages IIB-IIIB treated with the same chemoradiotherapy regimen were enrolled and genotyped for GSTM1, T1 and P1 gene polymorphisms by multiplex polymerase chain reaction (mPCR) and PCR-restriction fragment length polymorphism (PCR-RFLP). Overall survival was evaluated using Kaplan-Meier survival function and Cox proportional hazards model. All data were analyzed using SPSS (version 21.0).
RESULTS: Stratified analysis showed that GSTM1 null (M1-) genotype was associated with a significantly better survival among patients with stage IIB cervical cancer (log-rank P = 0.004) than cases with stage IIIA/IIIB. Death and recurrence were significantly higher in patients with GSTM1 present genotype (M1+) (P = 0.037 and P = 0.003 respectively) and those with M1- showed reduced hazard of death with an adjusted hazard ratio 'HR' of 0.47 (95% CI, 0.269-0.802, P = 0.006). Women with M1- genotype as well as in combination with GSTT1 null (T1-), GSTP1 (AG+GG) and GSTT1 null/GSTP1 (AG+GG) showed better survival and also reduced risk of death (HR = 0.31, P = 0.016; HR = 0.45, P = 0.013; HR = 0.31, P = 0.02 respectively).
CONCLUSIONS: To the best of our knowledge, this is the first study to correlate the association of GSTM1, T1 and P1 gene polymorphisms with treatment outcome of CRT treated CC patients. Our results suggested that individuals with GSTM1 null genotype and in combination with GSTT1 null and GSTP1 (AG+GG) had a survival advantage. Such genetic studies may provide prognostic information in CRT treated CC patients.

Soto-Quintana O, Zúñiga-González GM, Ramírez-Patiño R, et al.
Association of the GSTM1 null polymorphism with breast cancer in a Mexican population.
Genet Mol Res. 2015; 14(4):13066-75 [PubMed] Related Publications
The glutathione S transferase (GST) family plays an important role in the processing of carcinogens. Data on the null GSTM1 genotype has revealed associations with cancer, and has been suggested to affect carcinogen metabolism and to contribute to tumor promotion in the mammary gland. We examined the role of the null GSTM1 genotype by comparing the genotypes of 276 healthy Mexican women with those of 558 Mexican women with breast cancer (BC). The genotype frequencies observed in the controls and patients with BC were 38 and 45% for the null GSTM1 genotype, respectively. The obtained odds ratio (OR) was 1.36, with a 95% confidence interval (95%CI) of 1.02-1.8, P = 0.04. The protective association was also evident upon analysis of the distributions of the null GSTM1 genotype in patients with positive chemotherapy response who had high plasma levels of glucose (OR 0.56, 95%CI = 0.33-0.94, P = 0.03). This study suggested that the null GSTM1 genotype is associated with BC susceptibility in the Mexican population analyzed.

Sharma N, Singh A, Singh N, et al.
Genetic polymorphisms in GSTM1, GSTT1 and GSTP1 genes and risk of lung cancer in a North Indian population.
Cancer Epidemiol. 2015; 39(6):947-55 [PubMed] Related Publications
BACKGROUND: A number of studies done so far in different populations have shown that polymorphisms within the GST genes play an important role in determining individual susceptibility to lung cancer; however, data obtained so far have been contradictory within the same or different populations. Few studies have focused on the combinatorial effect of the GST genes on susceptibility to lung cancer and also for different histological subtypes. Our aim is to investigate the roles of GSTM1, GSTT1, and GSTP1 polymorphisms as genetic modifiers of risk for lung cancer and histological subtypes using a larger sample size in a North Indian population.
METHODS: In total 540 subjects (270 lung cancer cases and 270 controls) were evaluated for the GST polymorphism. Genotyping for the GSTM1, GSTT1 and GSTP1 gene was done by using a multiplex PCR and PCR-RFLP method.
RESULTS: GSTM1 null genotype was found to be associated with lung cancer (OR=1.65, 95%CI: 116-2.3, P=0.005) and this risk was higher in cases of adenocarcinoma (ADCC). GSTT1 and GSTP1 did not show any significant association with lung cancer; however, when stratified for histological subtypes a significant association was observed for ADCC and small-cell lung cancer (SCLC) for both GSTT1 null and variant GSTP1 genotypes. The combined 'at risk' genotypes of null GSTM1 and GSTT1 genes were found to be associated with lung cancer risk, and this risk was higher in cases of ADCC (OR=4.09, 95%CI: 110-10.2, P=0.002). There is a twofold increased risk for lung cancer with the null GSTM1 and wild-type GSTP1 genotypes (P=0.0004); similarly, a fourfold increased risk was observed with the null GSTT1 and wild-type GSTP1 genotypes (P=0.0001).
CONCLUSIONS: The deficient GST genotypes seem thus to be important risk modifiers for lung cancer and related histological subtypes, especially in combination.

Li XM, Yu XW, Yuan Y, et al.
Glutathione S-transferase P1, gene-gene interaction, and lung cancer susceptibility in the Chinese population: An updated meta-analysis and review.
J Cancer Res Ther. 2015 Jul-Sep; 11(3):565-70 [PubMed] Related Publications
AIM OF STUDY: To assess the impact of glutathione S-transferase P1 (GSTP1) Ile105Val polymorphism on the risk of lung cancer in the Chinese population, an updated meta-analysis and review was performed.
MATERIALS AND METHODS: Relevant studies were identified from PubMed, Springer Link, Ovid, Chinese Wanfang Data Knowledge Service Platform, Chinese National Knowledge Infrastructure, and Chinese Biology Medicine published through January 22, 2015. The odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to estimate the strength of the associations.
RESULTS: A total of 13 case-control studies, including 2026 lung cancer cases and 2451 controls, were included in this meta-analysis. Overall, significantly increased lung cancer risk was associated with the variant genotypes of GSTP1 polymorphism in the Chinese population (GG vs. AA: OR=1.36, 95% CI=1.01-1.84). In subgroup analyses stratified by geographic area and source of controls, the significant results were found in population-based studies (GG vs. AA: OR=1.62, 95% CI: 1.13-2.31; GG vs. AG: OR=1.49, 95% CI: 1.03-2.16; GG vs. AA+AG: OR=1.55, 95% CI: 1.12-2.26). A gene-gene interaction analysis showed that there was an interaction for individuals with combination of GSTM1 (or GSTT1) null genotype and GSTP1 (AG+GG) mutant genotype for lung cancer risk in Chinese.
CONCLUSION: This meta-analysis suggests that GSTP1 Ile105Val polymorphism may increase the risk of lung cancer in the Chinese population.

Sharma A, Gupta S, Sodhani P, et al.
Glutathione S-transferase M1 and T1 Polymorphisms, Cigarette Smoking and HPV Infection in Precancerous and Cancerous Lesions of the Uterine Cervix.
Asian Pac J Cancer Prev. 2015; 16(15):6429-38 [PubMed] Related Publications
Glutathione S-transferases (GSTs) play an important role in detoxification of carcinogenic electrophiles. The null genotypes in GSTM1 and GSTT1 have been implicated in carcinogenesis. Present study was planned to evaluate the influence of genetic polymorphisms of GSTM1 and GSTT1 gene loci in cervical carcinogenesis. The study was conducted in Lok Nayak hospital, New Delhi. DNA from clinical scrapes of 482 women with minor gynaecologic complaints attending Gynaecology OPD and tumor biopsies of 135 cervical cancer cases attending the cancer clinic was extracted. HPV DNA was detected by standard polymerase chain reaction (PCR) using L1 consensus primer pair. Polymorphisms of GSTM1 and GSTT1 were analysed by multiplex PCR procedures. Differences in proportions were tested using Pearson's Chi-square test with Odds ratio (OR) and 95% confidence interval (CI). The risk of cervical cancer was almost three times in women with GSTM1 homozygous null genotype (OR-2.62, 95%CI, 1.77-3.88; p<0.0001). No association of GSTM1 or GSTT1 homozygous null genotypes was observed in women with normal, precancerous and cervical cancerous lesions among ≤35 or >35 years of age groups. Smokers with null GSTT1 genotype had a higher risk of cervical cancer as compared to non-smokers (OR-3.01, 95% CI, 1.10-8.23; p=0.03). The results further showed that a significant increased risk of cervical cancer was observed in HPV positive smoker women with GSTT1 (OR-4.36, 95% CI, 1.27-15.03; p=0.02) and GSTM1T1 (OR-3.87, 95% CI, 1.05-14.23; p=0.04) homozygous null genotypes as compared to HPV positive non smokers. The results demonstrate that the GST null genotypes were alone not associated with the development of cervical cancer, but interacted with smoking and HPV to exert effects in our Delhi population.

Cao DL, Ye DW, Dai B, et al.
Association of glutathione S-transferase T1 and M1 polymorphisms with prostate cancer susceptibility in populations of Asian descent: a meta-analysis.
Oncotarget. 2015; 6(34):35843-50 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: Genetic polymorphism was hypothesized to be reason of variation in prostate cancer incidence among different racial group. Based on that published data on the association of prostate cancer susceptibility with polymorphisms in genes encoding Glutathione S-transferases (GSTs) were inconclusive, the aim of this study was to more precisely address the role of GSTs polymorphisms (especially, GSTT1 and GSTM1 deletions) on prostate cancer risk in Asian descent.
METHODS: A meta-analysis including 8 articles with 711 cases and 1122 controls for GSTT1 and 1098 cases and 1588 controls for GSTM1 was performed.
RESULTS: Significantly increased prostate cancer risk was found among subjects carrying GSTM1 null genotype (odds ratio (OR) = 1.403; 95% confidence interval (CI) = 1.088 - 1.808) but not among subjects carrying GSTT1 deletion genotype (OR = 0.959; 95%CI = 0.709 - 1.297). When stratified by country, the null genotype of GSTT1 neither increased nor decreased prostate cancer risk significantly in China (OR = 1.355; 95%CI = 0.895 - 2.049), Japan (OR = 0.812; 95%CI = 0.545 - 1.211), and Korea (OR = 1.056; 95%CI = 0.727 - 1.534). While significant association of elevated prostate cancer risk with GSTM1 deletion were found in China (OR = 1.665; 95%CI = 1.324 - .094) and Korea (OR = 1.914; 95%CI = 1.311 - 2.793) but not in Japan (OR = 0.980; 95%CI = 0.726 - 1.321).
CONCLUSIONS: In summary, this meta-analysis suggested that the null genotype of GSTM1 rather than GSTT1 may be involved in the etiology of prostate cancer in Asian population.

Kimi L, Ghatak S, Yadav RP, et al.
Relevance of GSTM1, GSTT1 and GSTP1 Gene Polymorphism to Breast Cancer Susceptibility in Mizoram Population, Northeast India.
Biochem Genet. 2016; 54(1):41-9 [PubMed] Related Publications
The enzymes encoded by glutathione S-transferase mu 1 (GSTM1) and theta 1 (GSTT1) genes are involved in the metabolism of wide range of carcinogens that are ubiquitous in the environment. Homozygous deletions of the GSTM1 and GSTT1 genes are commonly found and result in lack of enzyme activity. This study was undertaken to evaluate the association between GSTM1, GSTT1 and GSTP1 gene polymorphism and breast cancer risk in Mizoram population. Odd ratio (OR) and 95% confidence interval (CI) from conditional logistic regression model were used to estimate the association between genetic polymorphism and breast cancer risk. The GSTM1 and GSTT1 null genotypes were associated with an increased risk of breast cancer [OR = 10.80 (95% CI 1.16-100.43)]. The risk of breast cancer associated with the GSTT1 null genotype was observed to be low among postmenopausal women. When considered together, GSTM1 and GSTT1 genotypes were found to be associated with an increased risk of breast cancer. The relationship between GSTM1 and GSTT1 gene deletions and breast cancer risk was substantially altered by consumption of Smoked Meat/Vegetable. In the present study, GSTP1Ile105Val (rs1695) polymorphism was related to breast cancer susceptibility or phenotype. Our data provides evidence for substantially increased risk of breast cancer associated with GSTM1 and/or GSTT1 homozygous gene deletions in Mizoram population.

Masood N, Mubashar A, Yasmin A
Epidemiological factors related to GSTM1 and GSTT1 genes deletion in colon and rectum cancers: A case-control study.
Cancer Biomark. 2015; 15(5):583-9 [PubMed] Related Publications
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.

Figueroa JD, Koutros S, Colt JS, et al.
Modification of Occupational Exposures on Bladder Cancer Risk by Common Genetic Polymorphisms.
J Natl Cancer Inst. 2015; 107(11) [PubMed] Free Access to Full Article Related Publications
Few studies have demonstrated gene/environment interactions in cancer research. Using data on high-risk occupations for 2258 case patients and 2410 control patients from two bladder cancer studies, we observed that three of 16 known or candidate bladder cancer susceptibility variants displayed statistically significant and consistent evidence of additive interactions; specifically, the GSTM1 deletion polymorphism (P interaction ≤ .001), rs11892031 (UGT1A, P interaction = .01), and rs798766 (TMEM129-TACC3-FGFR3, P interaction = .03). There was limited evidence for multiplicative interactions. When we examined detailed data on a prevalent occupational exposure associated with increased bladder cancer risk, straight metalworking fluids, we also observed statistically significant additive interaction for rs798766 (TMEM129-TACC3-FGFR3, P interaction = .02), with the interaction more apparent in patients with tumors positive for FGFR3 expression. All statistical tests were two-sided. The interaction we observed for rs798766 (TMEM129-TACC3-FGFR3) with specific exposure to straight metalworking fluids illustrates the value of integrating germline genetic variation, environmental exposures, and tumor marker data to provide insight into the mechanisms of bladder carcinogenesis.

Liu H, Jia J, Mao X, Lin Z
Association of CYP1A1 and GSTM1 Polymorphisms With Oral Cancer Susceptibility: A Meta-Analysis.
Medicine (Baltimore). 2015; 94(27):e895 [PubMed] Free Access to Full Article Related Publications
Our meta-analysis was aimed to evaluate the association of CYP1A1 and glutathione-S-transferase M1 (GSTM1) polymorphisms with oral cancer susceptibility.The related articles were searched in PubMed, Embase, and CNKI databases. Fifty eligible studies were included in our meta-analysis. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to evaluate the relationship of CYP1A1 (rs4646903 and rs1048943) and GSTM1 polymorphisms with oral cancer risk. A random-effects model or fixed-effects model was employed depending on the heterogeneity.In overall analysis, CYP1A1 rs4646903 polymorphism was associated with the risk of oral cancer (CC vs TT: OR 1.65, 95% CI 1.33-2.05; CC vs TC+TT: OR 1.77, 95% CI 1.48-2.11; C vs T: OR 1.17, 95% CI 1.07-1.28), whereas rs1048943 showed no obvious association with oral cancer susceptibility. Moreover, subgroup analysis by ethnicity demonstrated that rs4646903 and rs1048943 both related with increased risk of oral cancer in Asians. Moreover, the analysis based on source of control suggested that rs4646903 could increase the risk for oral cancer in both population- and hospital-based populations, whereas no remarkable relationship of rs1048943 with oral cancer susceptibility was observed. For GSTM1 gene, null genotype appeared to be a risk factor for oral cancer (null vs present: OR 1.23, 95% CI 1.12-1.34), which was also proved in the subgroup analysis.The results demonstrated that CYP1A1 rs4646903 and null genotype of GSTM1 polymorphisms might serve as risk factors for oral cancer.

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