Impact of glutathione S-transferase M1 and T1 gene polymorphisms on the smoking-related coronary artery disease

Glutathione S-transferase (GST) plays a key role in the detoxification of xenobiotic atherogen generated by smoking. To analyze the effect of GSTM1/T1 gene polymorphisms on the development of smoking-related coronary artery disease (CAD), 775 Korean patients who underwent coronary angiography were enrolled. The subjects were classified by luminal diameter stenosis into group A (>50%), B (20-50%), or C (<20%). GSTM1 and GSTT1 gene polymorphisms were analyzed using multiplex polymerase chain reaction (PCR) for GSTM1/T1 genes and CYP1A1 gene for internal control. Of 775 subjects, 403 patients belonged to group A. They had higher risk factors for CAD than group B (N=260) and group C (N=112). The genotype frequencies of null GSTM1 and GSTT1 showed no significant differences among 3 groups. Considering the effect of GSTM1 gene polymorphisms on the smoking-related CAD, smokers with GSTM1 null genotype had more increased risk for CAD than non-smoker with GSTM1 positive genotype (odds ratios [OR], 2.07, confidence interval [CI], 1.06-4.07). Also the effect of GSTT1 gene polymorphism on smoking-related CAD showed the same tendency as GSTM1 gene (OR, 2.00, CI, 1.05-3.84). This effect of GSTM1/T1 null genotype on smoking-related CAD was augmented when both gene polymorphisms were considered simultaneously (OR, 2.76, CI, 1.17-6.52). We concluded that GSTM1/T1 null genotype contributed to the pathogenesis of smoking-related CAD to some degree.     

Glutathione S-transferases genetic polymorphisms and human diseases: overview of epidemiological studies

Glutathione S-transferases (GST), xenobiotic-metabolising enzymes, are involved in the metabolic detoxification of various environmental carcinogens. Particular genetic polymorphisms of these enzymes have been shown to influence individual susceptibility against various pathologies including cancer, cardiovascular and respiratory diseases. The results from the meta-analysis indicate that GSTM1*0 null allele was associated with enhanced risk for lung (OR (95% IC) = 1,17 (1,07-1,27)), bladder (OR = 1,44 (1,23-1,68) and larynx cancer (OR = 1,42 (1,10-1,84)). GSTT1 null genotype was associated with increased astrocytomas (OR = 2,36 (1,41-3,94)) and meningiomas (OR = 3,57 (1,82-6,92)) cancer risk. GSTP1 allelic polymorphism influence the development of bladder cancer in smokers (OR = 2,40 (1,12-4,95)) and occupational asthma (OR = 3,5 (2,7-4,6)). Finally, GSTM1*0 null allele and GSTT1*1 functional allele were associated with increased risk for coronary heart diseases in smokers (OR = 2,30 (1,40-9,00)) and OR = 2,5 (1,30-4,80), respectively). The GSTT1*1 functional allele was also significantly associated with increased risk of lower extremity arterial disease (OR = 3,60 (1,40-9,00). These epidemiological data suggest that genetic GST polymorphisms influence the individual susceptibility to these diseases. Contrary to cardiovascular disease, no evidence of interaction between GST genotype and smoking status was found in lung cancer but it has not been studied in other cancers. Consequently, other works are necessary to study the potential interaction between GST genotype and environmental carcinogens including tobacco smoke extract.     

Interaction of passive smoking with GST (GSTM1, GSTT1, and GSTP1) genotypes in the risk of cervical cancer in India

Human papilloma virus (HPV) infection is a major cause of cervix cancer, but a number of infected women do not develop invasive lesions, suggesting that HPV infection in itself is not a sufficient factor and that other cofactors, such as smoking, play an important role in development of cervix cancer. Alongside active cigarette smoking, passive smoking is an independent risk factor for cervix cancer. Smoking maintains cervical HPV infection longer and decreases potential of clearing an oncogenic infection. Thus, it is quite possible that polymorphism at detoxifying enzyme coding loci such as GSTM1, GSTT1, and GSTP1 may determine susceptibility to cervix cancer. This study evaluates the combined effects of genetic polymorphisms of GSTM1, GSTT1, and GSTP1 on susceptibility to cervical cancer and interaction of these genes with smoking. On individual analysis of GSTM1, GSTT1, and GSTP1, it was observed that passive smokers having genotypes GSTM1 (null) (OR = 7.0, 95% CI = 2.19-22.36, P = 0.0005), GSTT1 (null) (OR = 10.2, 95% CI = 1.23-84.18, P = 0.02), and GSTP1 (ile/val) (OR = 6.4, 95% CI = 2.25-18.38, P = 0.0005) have an increased risk of developing cervix cancer. It is thus concluded that cervical cancer risk is increased in passive smokers with GSTM1 (null), GSTT1 (null), and GSTP1 (ile/val) genotypes.     

Genetic polymorphisms in the cytochrome P450 1A1, glutathione S-transferase M1 and T1, and susceptibility to colon cancer

Several polymorphic cytochrome P-450 and glutathione S-transferase (GST) enzymes are involved in the activation and detoxification of many potential carcinogens and may therefore be important in susceptibility to cancer induction. CYP1A1 MspI, GSTM1, and GSTT1 are polymorphic enzymes and some alleles have been correlated with an increased risk of developing some cancers. In the present study, we examined possible associations between genetic polymorphisms of CYP1A1 MspI, GSTM1, and GSTT1 and colon cancer in a United Kingdom population. An excess of CYP1A1 MspI, and GSTM1 null genotypes was observed amongst colon cancer patients, although this did not reach the level of statistical significance. We found no significant increase in the risk of colon cancer for either CYP1A1 MspI (OR = 1.39; 95%CI: 0.46-4.21) or GSTM1 null (OR = 1.41; 95%CI: 0.76-3.01) genotypes. Individuals with GSTT1 null genotype had no association with colon cancer (OR = 0.42; 95%CI: 0.09-2.02). No significant association was observed in the site of colon cancer (proximal vs. distal). This study suggests that the polymorphisms of CYP1A1 MspI, GSTM1, and GSTT1 are not associated with a significant risk of developing colon cancer in a United Kingdom population.     

Combined effect of smoking and inherited polymorphisms in arylamine N-acetyltransferase 2, glutathione S-transferases M1 and T1 on bladder cancer in a Tunisian population

Cigarette smoking is the predominant risk factor for bladder cancer in males and females. The tobacco carcinogens are metabolized by various xenobiotic metabolizing enzymes, such as the super-families of N-acetyltransferases (NAT) and glutathione S-transferases (GST). Polymorphisms in NAT and GST genes alter the ability of these enzymes to metabolize carcinogens. We have conducted this case-control study to assess the role of smoking, slow NAT2 variants, and GSTM1 and GSTT1 null genotypes in bladder cancer development in North Tunisia. In all groups of patients, we have shown that GSTM1 and GSTT1 null genotypes did not appear to be a factor affecting bladder cancer susceptibility. For the NAT2 slow acetylator genotype, the NAT2*5/*7 diplotype was found to have a 7-fold increased risk of bladder (OR=7.14; 95% CI: 1.30–51.41). Furthermore, we found that NAT2 slow acetylator individuals temporarily carrying wild-type GSTT1 or GSTM1 null genotypes have a strong increased risk of bladder cancer (OR= 26 and 22.17, respectively). This cumulative effect was estimated at 12 for smokers harboring slow or an intermediate NAT2, GSTM1 null, and wild-type GSTT1 genotypes compared to non-smokers carrying rapid NAT2, wild-type GSTM,1 and GSTT1 null genotypes (p=0.02; OR=12; CI 95% 1–323.76).     

Genetic polymorphism of the glutathione S-transferase M1 and T1 genes in three distinct Arab populations

Deletion polymorphisms for the glutathione S-transferase (GST) gene are associated with increased risk of cancer, and are implicated in detoxifying mutagenic electrophilic compounds. GST Polymorphic variants were reported for different populations. The aim of this study was to investigate the frequencies of GSTM1 and GSTT1 null genotypes among Bahraini, Lebanese and Tunisian Arabs. GST genotyping was done by multiplex PCR-based methods. Study subjects comprised 167 Bahrainis, 141 Lebanese and 186 Tunisians unrelated healthy individuals. GSTM1 deletion homozygosity of 49.7%, 52.5% and 63.4% were recorded for Bahraini, Lebanese and Tunisians, respectively. Among Bahrainis, the prevalence of GSTT1 null homozygotes was 28.7%, while in higher rates were seen in Lebanese (37.6%) and Tunisians (37.1%). Our results indicate that there are no major differences in allelic distribution of GSTM1 and GSTT1 genes between the three Arab populations investigated except between Bahrainis and Tunisians regarding the allelic distribution of GSTM1 gene (P=0.013). Combined analysis of both genes revealed that 14.4% of Bahrainis, 16.3% of Lebanese and 21.0% of Tunisians harbor the deleted genotype of both genes. This is the first study that addresses GST gene polymorphism in Bahraini and Lebanese Arabs, and will help genetic studies on the association of GSTM1 and GSTT1 polymorphisms with disease risks and drug effects in Arab populations.     

Interaction of glutathione-s-transferase genotypes with environmental risk factors in determining susceptibility to head and neck cancer and treatment response and survival outcome

The present case-control study aimed to investigate the role of interaction of glutathione-s-transferase (GST) genotypes with environmental risk factors in determining susceptibility to head and neck squamous cell carcinoma (HNSCC) involving 1,250 cases and equal number of healthy controls. An increase in the risk of HNSCC and its subsites (larynx, pharynx, and oral cavity) was observed among the cases with null genotypes of GSTM1 (odds ratio [OR] = 1.87) or GSTT1 (OR = 1.39) while reduced risk (OR = 0.81) was observed the cases with variant genotype of GSTP1. Tobacco use in the form of smoking or chewing interacted multiplicatively with GSTM1 or GSTT1 to increase the risk several folds (3–10 folds) in HNSCC and its subsites. Alcohol use also increased the risk (2–3 folds) to HNSCC and its subsites in cases with null or variant genotypes of GSTs, though this risk was of lesser magnitude when compared to the tobacco users. A synergistic effect of both, tobacco smoking and alcohol drinking, led to several folds (25-folds) increased risk to HNSCC among the cases with null genotype of GSTM1 and GSTT1 when compared to nonsmokers and nondrinkers with wild genotype of GSTM1 and GSTT1 in controls. Furthermore, cases with variant genotypes of GSTP1 (Val/Val) showed superior treatment response with improved survival rate and lower risk of death when compared to the patients with wild type genotype (Ile/Ile). The data suggest that though polymorphism in GSTs may be a modest risk factor for determining HNSCC risk, gene-environment interactions significantly modify the susceptibility to HNSCC by several folds.     

Association between glutathione S-transferase gene M1 and T1 polymorphisms and chronic obstructive pulmonary disease risk: A meta-analysis

Chronic obstructive pulmonary disease (COPD) is a severe lung disease characterized by long-term breathing problems. A series of studies have indicated that the glutathione S-transferase genes M1 and T1 are associated with COPD susceptibility; however, the result still remains inconclusive. This meta-analysis was performed to estimate the effect of GSTM1 and GSTT1 polymorphisms in COPD risk. Eligible case-control studies published between January 2000 and December 2017 was searched and retrieved. A total of 37 articles were screened out, including 4674 COPD patients and 5006 controls. Overall, our results found that GSTM1 and GSTT1 null genotypes significantly increased the risk of COPD (GSTM1: odds ratio [OR] = 1.52, 95% confidence interval [CI] = 1.31-1.77, P <.00001; GSTT1: OR = 1.28, 95% CI = 1.09-1.50, P = .003). Subgroup analysis by ethnicity suggested that there was a close association between GSTM1 null polymorphism and COPD susceptibility in each studied ethnicity, while GSTT1 null polymorphism only showed association with Asian COPD patients. Moreover, we also found that joint GSTM1/GSTT1 null genotypes showed a high association with increased COPD susceptibility (OR = 1.42, 95% CI = 1.21-1.66, P < .0001). In conclusion, our results indicated that GSTM1 null, GSTT1 null, and the combined GSTM1/GSTT1 null genotypes might be risk factors in the development of COPD. However, future case-control studies with large-scale participants are still required to further estimate these associations.     

Relationship between glutathione S-transferase gene polymorphisms and enzyme activity in Hong Kong Chinese asthmatics

BACKGROUND: Asthma is a disease associated with oxidative stress. The glutathione S-transferases (GST) are a group of enzymes that protect cells from oxidative stress. Functional genetic polymorphisms of GST genes (GSTT1, GSTM1 and GSTP1) have previously been reported. OBJECTIVE: To investigate the association of GST gene polymorphisms and its enzyme activity with the risk of asthma in Hong Kong Chinese adults. METHODS: An age- and smoking status-matched case-control study was carried out on 315 patients with asthma and 315 healthy controls. Genotyping was carried out on genomic DNA using the PCR and/or restriction fragment length polymorphism (PCR-RFLP). Plasma GST activity was measured by fluorometric assay. RESULTS: The distribution of various genotypes or alleles of the GSTT1, GSTM1 and GSTP1 was not significantly different between patients with asthma and healthy controls. The GSTM1 null genotype was found to be protective from the development of asthma in atopic subjects (odds ratios 0.55, 95% confidence interval 0.34-0.90; P=0.017). However, there was no association between GSTT1 and GSTM1 null genotypes and enzyme activity. GSTP1 codon 105 Val variants led to reduced plasma GST activity in healthy controls. Asthma patients had elevated plasma GST activity compared with healthy controls irrespective of their genotypes (P<0.001). CONCLUSION: Our data suggest that among atopic subjects, the GSTM1 null genotype is associated with a decreased risk for asthma despite increased level of plasma GST activity in asthma, but it could not distinguish whether this increase is a potentially protective compensatory effect or a pathogenic factor.     

The role of glutathione transferases M1 and T1 in individual susceptibility to bladder cancer in a Tunisian population

BACKGROUND: Susceptibility to bladder cancer is thought to depend on interplay between genetic factors and environmental chemical carcinogens. AIM: This study seeks to determine the role of the glutathione transferases M1 and T1 null genotypes (GSTM1*0 and GSTT1*0) in individual susceptibility to bladder cancer in a Tunisian population. METHOD: Sixty-two patients with transitional cell carcinoma of the bladder cancer and 79 controls were examined with respect to the frequency of GSTM1 and GSTT1 null genotypes. RESULTS: The frequencies of the GSTT1 null in the total group of bladder cancer cases vs. controls did not differ statistically. The proportion of GSTM1 null genotype in patients was 63% compared to 45% in controls group (OR = 2.03; 95% CI 0.97-4.24; p = 0.04). A significantly higher incidence of GSTM1 deletion genotype was found in smokers with bladder cancer compared to the controls (65.38% vs. 45.5%). Smokers lacking the GSTM1 gene are at an approximately 2.2-fold higher risk of bladder cancer (OR= 2.23, 95% CI 1-5.15; p = 0.03). CONCLUSION: This study suggests that in Tunisian subjects the GSTM1 null genotype may be associated with an increased risk of bladder cancer. This association appears to depend upon smoking status.     

谷胱甘肽硫转移酶M1和T1基因多态性与肺癌易感性关系的研究

目的和方法:采用病例-对照研究方法和多重PCR技术检测肺癌病例组161人和健康对照组165人的GSTM1(glutathioneS-transferaseM1)和GSTT1(glutathioneS-transferaseT1)基因缺陷型的频率,以多因素Logistic回归模型评价GSTM1和GSTT1基因型之间以及基因型与吸烟之间的交互作用。以探讨谷胱甘肽硫转移酶M1和T1的基因多态性与肺癌发病的关系。结果:GSTM1基因缺陷型和GSTT1基因缺陷型的频率在病例组和对照组之间均无显著的差异。在不吸烟(SI=0)的人群中,GSTM1基因缺陷型携带者患肺癌的危险性显著增加。此外,该基因型还可显著增加年龄≥60岁者患肺腺癌的危险性。多因素Logistic回归分析显示吸烟和GSTM1基因缺陷型是肺癌的危险因素,吸烟与GSTM1和GSTT1基因型不存在交互作用。分层分析表明GSTT1基因功能型与GSTM1基因缺陷型存在明显的交互作用,在年龄≥60岁的人群及不吸烟的人群中,GSTT1基因功能型可以使得GSTM1基因缺陷型携带者患肺腺癌的危险度分别降低48.5%和45.3%。结论:GSTM1基因缺陷型是非吸烟者和年龄≥60岁者患肺癌,尤其是患肺腺癌的危险因素,GSTT1基因功能型可以降低不吸烟或年龄≥60岁的GSTM1基因缺陷型携带者患肺腺癌的危险度。在肺癌的发生过程中GSTM1和GSTT1基因缺陷型与吸烟不存在交互作用。     

GSTT1 Gene Deletion Is Associated with Lung Cancer in Mexican Patients

Glutathione S-transferase (GST) is a dimeric detoxifying isoenzyme, involved in the deactivation of carcinogens, several tobacco-derived carcinogens, and xenobiotics. It catalyzes the reduction of glutathione to its thioester; thus, deficiency in GST activity due to homozygous deletion of the GSTT1 gene (null genotype) may play a role in the induction of lung cancer by smoking.We studied the distribution of GSTT1 gene deletion in peripheral blood DNA samples from 178 healthy controls (41 nonsmokers, 63 passive smokers and 74 smokers) and 52 lung cancer patients. Comparisons between groups showed that there was an increased lung cancer risk for individuals with the GSTT1 null genotype. Cancer patients showed significant differences when compared with controls: nonsmokers, passive smokers, and smokers. Twenty-one percent of lung cancer patients carried the deletion versus 2% among nonsmokers not exposed to passive smoking, 6% among passive smokers, and 5% among smokers. Thus, there is a significant association between this genotype and the possibility to risk of developing lung cancer.     

GSTT1 gene deletion is associated with lung cancer in Mexican patients

Glutathione S-transferase (GST) is a dimeric detoxifying isoenzyme, involved in the deactivation of carcinogens, several tobacco-derived carcinogens, and xenobiotics. It catalyzes the reduction of glutathione to its thioester; thus, deficiency in GST activity due to homozygous deletion of the GSTT1 gene (null genotype) may play a role in the induction of lung cancer by smoking. We studied the distribution of GSTT1 gene deletion in peripheral blood DNA samples from 178 healthy controls (41 nonsmokers, 63 passive smokers and 74 smokers) and 52 lung cancer patients. Comparisons between groups showed that there was an increased lung cancer risk for individuals with the GSTT1 null genotype. Cancer patients showed significant differences when compared with controls: nonsmokers, passive smokers, and smokers. Twenty-one percent of lung cancer patients carried the deletion versus 2% among nonsmokers not exposed to passive smoking, 6% among passive smokers, and 5% among smokers. Thus, there is a significant association between this genotype and the possibility to risk of developing lung cancer.     

Glutathione S-transferase Mu null genotype affords protection against alcohol induced chronic pancreatitis

Glutathione S-transferases (GSTs) play critical roles in providing protection against electrophiles and products of oxidative stress, by catalysing the formation of glutathione conjugates and by eliminating peroxides. Most extensively studied are four main families of human cytosolic GST: GSTAlpha(A), GSTMu(M), GSTPi(P) and GSTTheta(T). Absence of GSTM1 or GSTT1 can be attributed to absence of the GSTM1 or GSTT1 gene products (null genotype) in approximately 50% and 20% of the Caucasian population, respectively. We investigated whether polymorphisms in the GSTM1, GSTT1 and GSTP1 genes modified the risk for chronic pancreatitis (CP). DNA samples were obtained from 142 adult CP patients with alcoholic (n = 79), hereditary (n = 21) or idiopathic (n = 42) origin. DNA from 204 healthy controls and from 57 alcoholic controls was analysed for comparison. Patients and controls were all of Caucasian origin. Genetic polymorphisms in GSTs were determined by PCR, eventually followed by restriction-fragment-length-polymorphism analyses in all subjects. The rates of GSTT1 and GSTP1 genotypes did not differ between CP patients and healthy controls. However, GSTM1 null genotypes were significantly less common in alcoholic CP patients (OR = 0.56, 95% CI: 0.33-0.95) as compared to healthy controls and to alcoholic controls (OR = 0.52, 95% CI: 0.26-1.04). Age- and sex-adjustment bolstered our finding (adjusted OR = 0.48, 95% CI: 0.26-0.89). The frequency of the GSTM1 null genotype is significantly lower in alcoholic CP patients, especially young female. This suggests that GSTM1 null alcohol users, particularly young female, are less susceptible to CP.     

Polymorphisms of the genes encoding the GSTM1, GSTT1 and GSTP1 in Korean women: no association with endometriosis

Endometriosis, one of the most common gynaecologic disorders, shows significantly elevated prevalence in industrial areas and there is also a possible genetic predisposition. Glutathione-S-transferases (GSTs) are enzymes involved in the metabolism of many disease-causing carcinogens and mutagens that are present in human environments. An association between the incidence of endometriosis and the GST genotypes of patients has been suggested. The objective of the present study was to investigate whether the polymorphisms of GSTM1, GSTT1 and GSTP1 are related to endometriosis. Blood samples were available from 259 controls and 194 patients with advanced endometriosis diagnosed by both pathology and laparoscopic findings. The proportion of the GSTM1, GSTT1 and GSTP1 genotypes of the control group were comparable to other populations. There was no significant evidence that the distribution of the GSTM1 and GSTT1 genotype differed between the patients and the controls, with an allelic odds ratio (OR)=1.074 [95% confidence interval (CI)=0.737-1.564] and 1.239 (95% CI = 0.853-1.799), respectively. Also, there was no significant difference in the proportion of GSTP1 genotypes between the women with endometriosis and the control group with the OR = 0.823 (95% CI = 0.536-1.264). The higher risk alleles were contended as GSTM1, GSTT1 null mutation and GSTP1 Ile105Ile polymorphism. There was no significant increase in the risk of endometriosis as the number of higher risk alleles of the GST family increased. In conclusion, our findings suggest that the GSTM1, GSTT1 and GSTP1 genetic polymorphisms are not associated with the development of endometriosis in Korean women.     

Genetic polymorphisms of GSTs and their association with primary brain tumor incidence

Glutathione S-transferases GSTM1, GSTT1, and GSTP1 are phase II biotransformation enzymes that function on detoxification of a wide range of exogenous agents including carcinogens. It has been shown that genetic variations in these genes play an important role in determining the response of an individual to environmental carcinogens. Some studies revealed a statistically significant association between the polymorphisms in the genes encoding GST enzymes and some cancers, although contrary reports exist. In this study, the association between polymorphisms in these genes and primary brain tumor incidence was investigated in 228 Turkish individuals (75 patients with primary brain tumor and 153 controls). The prevalence of GSTM1 null genotype in the case group was 43%, compared to 24% in the control group, giving an odds ratio (OR) of 2.33 (95% confidence interval CI=1.24-4.39). No association was observed between the GSTT1 or GSTP1 Ile105Val polymorphism and brain tumor incidence. Polymorphisms in GSTM1, GSTT1, and GSTP1 did not show association with histopathologic type of brain tumor (glioma or meningioma). Analysis of the polymorphisms in the studied genes and smoking status of the brain tumor patients revealed no statistically significant association. The presented data clearly suggest a relation between brain tumor incidence with GSTM1 null genotype but not with GSTT1 or GSTP1 gene variants.     

The role of glutathione transferases M1 and T1 in individual susceptibility to bladder cancer in a Tunisian population

Background: Susceptibility to bladder cancer is thought to depend on interplay between genetic factors and environmental chemical carcinogens.

Aim: This study seeks to determine the role of the glutathione transferases M1 and T1 null genotypes (GSTM1*0 and GSTT1*0) in individual susceptibility to bladder cancer in a Tunisian population.

Method: Sixty-two patients with transitional cell carcinoma of the bladder cancer and 79 controls were examined with respect to the frequency of GSTM1 and GSTT1 null genotypes.

Results: The frequencies of the GSTT1 null in the total group of bladder cancer cases vs. controls did not differ statistically. The proportion of GSTM1 null genotype in patients was 63% compared to 45% in controls group (OR?=?2.03; 95% CI 0.97–4.24; p?=?0.04). A significantly higher incidence of GSTM1 deletion genotype was found in smokers with bladder cancer compared to the controls (65.38% vs. 45.5%). Smokers lacking the GSTM1 gene are at an approximately 2.2-fold higher risk of bladder cancer (OR?=?2.23, 95% CI 1–5.15; p?=?0.03).

Conclusion: This study suggests that in Tunisian subjects the GSTM1 null genotype may be associated with an increased risk of bladder cancer. This association appears to depend upon smoking status.     

Glutathione S-transferase T1 status and gastric cancer risk: a meta-analysis of the literature

To clarify the risk of gastric cancer associated with glutathione S-transferase T1 (GSTT1) status, a meta-analysis of published studies was performed. Eligible studies included all reports investigating an association between GSTT1 status and gastric cancer published before October 31, 2005. A qualitative scoring of papers was applied to evaluate the quality of the published data. The principal outcome measure was the odds ratio (OR) for the risk of gastric cancer associated with GSTT1 deletion status using a random effects model. Eighteen case-control studies detailing a possible association between the GSTT1 null genotype and gastric cancer were selected. Combining data from these studies, totalling 2508 cases and 4634 controls, a non-statistically significant OR for gastric cancer risk associated with GSTT1 deficiency emerged [OR = 1.09; 95% confidence interval (CI): 0.97-1.21; I(2) = 0%]. When only high-quality scored studies were considered, a statistically significant increased risk appeared (OR = 1.23; 95% CI: 1.04-1.45; I(2) = 0%), as well as considering only Caucasians (OR = 1.23; 95% CI: 1.03-1.56; I(2) = 0%). By pooling data from seven studies (319 cases and 656 controls) that considered combinations of GSTT1 and GSTM1 genotypes, a statistically significant increased risk for gastric cancer (OR = 1.95, 95% CI: 1.42-2.67; I(2) = 0%) was detected for individuals with deletion mutations in both genes compared with wild-types. In conclusion, this meta-analysis suggests that the GSTT1 null genotype may slightly increase the risk of gastric cancer and that interaction between unfavourable GST genotypes may exist. Greater attention should, therefore, be paid to the design of future studies; the investigation of interactions among multiple genotypes and environmental exposures are justified to clarify GSTT1 null status influence on gastric cancer risk.     

Glutathione S-transferase T1 (GSTT1) and M1 (GSTM1) genes polymorphism and risk of bronchial asthma in children

Oxidative stress is thought to be involved in the pathogenesis of asthma. Glutathione S-transferase (GST) enzymes play an important role in the antioxidant defence mechanism and therefore may influence asthma risk. Polymorphism of GSTT1 and GSTM1 genes has been associated with asthma in children and adults, but results are inconsistent across studies. The aim of the present study was to examine the association of GSTT1 and GSTM1 gene genotypes and the risk of asthma among 44 stable asthmatic children in comparison to 30 healthy control subjects. Genotyping was performed using the multiplex PCR technique. GSTT1 null genotype was significantly associated with an increased risk of asthma by more than 9-fold. GSTM1 polymorphism did not appear to play a major role in the development of bronchial asthma in children. Neither was associated with patients’ phenotype.     

Genetic Polymorphism of Glutathione S Transferases M1 and T1 in Indian Patients with Hepatocellular Carcinoma

Objective: Our aim was to evaluate whether the association of GSTM1/T1 gene polymorphisms modifies the risk of Hepatocellular carcinoma (HCC) and what is its correlation with other predisposing risk factors like alcohol intake, cigarette smoking and hepatitis B and C infections. Study design/setting: It was a case-control study, included 254 HCC cases compared with 525 hospital-based age and sex matched cases of chronic liver disease without HCC as controls from Indian population. The GSTM1 and GSTT1 genotypes were detected using conventional multiplex PCR method. Results: In this case-control study, we observed a positive correlation between age, HBV and HCV infection, smoking habit of > 20 packs/year, alcohol consumption of > 100 g/day and risk of liver cancer. We found significantly increased risk associated with GSTM1 null genotype (OR = 3.49; 95% CI = 2.52–4.84) as well as GSTT1 null genotype (OR = 3.12; 95% CI = 2.19–4.45), respectively. However, an increased risk of HCC was observed among heavy drinkers with GSTM1 (OR = 2.01; 95% CI = 1.11–3.66). Further, cigarette smoking showed a non-significant association with GSTT1 (OR = 1.49; CI = 0.69–3.25). Conclusion: Our results suggest that the variants in low penetrance gene such as GSTM1 and GSTT1 are associated with an increased liver cancer risk. Further, an influence of GSTM1/T1 null genotypes may contribute in the etiology of HCC in patients with higher cigarette and alcohol consumption.