Abnormal liver function associated with occupational exposure to dimethylformamide and glutathione S-transferase polymorphisms.

Dimethylformaide (DMF) is a major solvent predominately used in synthetic leather and resin production. Many human and animal studies have linked the cause of hepatoxicity to DMF. Previously, the authors demonstrated the significant dose-response relationship between abnormal liver function tests and DMF exposure and the interaction with hepatitis B virus (HBV) infection in Taiwanese workers. Because the toxic effect of various chemicals can be modified by metabolic traits, the study also investigated the influence of the glutathione S-transferases (GSTM1 and GSTT1) on the toxic effect of DMF. The average DMF exposure concentration was 23.87 ppm (range 5.2-86.6 ppm) in the high-exposure (>/=5 ppm) group and 2.41 ppm (range 0.9-4.3 ppm) in the low-exposure (<5 ppm) group. There were 13 of 44 (29.6%) abnormal liver function tests (elevations of either glutamate oxaloacetate transaminase (GOT) or glutamate pyruvate transaminase (GPT)) among the high DMF exposure workers, two of 22 (9.1%) abnormal liver function tests among the low DMF exposure workers. Chronic liver disease as determined by ultrasonography was present in seven of 44 (15.9%) high DMF exposure workers, and 0 of 22 (0%) low DMF exposure workers. There were 11 of 34 (32.4%) abnormal liver function tests among the GSTT1 null genotype workers, and four of 32 (12.5%) abnormal liver function tests among the GSTT1-positive genotype workers. Compared with the low DMF exposure workers, the adjusted odds ratio and 95% confidence intervals for abnormal liver function tests was 6.78 (0.94-48.7) for the high DMF exposure workers. Compared with the GSTT1-positive genotype workers, the adjusted odds ratio and 95% confidence intervals for abnormal liver function tests was 4.41 (1.15-16.9) for the GSTT1 null genotype workers. Compared with the low DMF group with GSTT1-positive genotype workers, the odds ratio (adjusted for HBV status) of abnormal liver function test was 12.38, 95% CI=(1.04-146.9) for the high DMF group with GSTT1 null genotype workers. This study indicates that abnormal liver function and chronic liver disease are associated with DMF exposure, and there are more than multiplicative interaction effects on abnormal liver function tests between the DMF exposure and the GSTT1 genotype.     

Null genotype of GSTT1 contributes to increased Parkinson’s disease risk in Caucasians: evidence from a meta-analysis

Conflicting results in previous case–control studies on the association between Glutathione S-transferase T1 (GSTT1) gene polymorphism and Parkinson’s disease (PD) risk have been reported, so we conducted this meta-analysis. We searched and extracted data from 3 Chinese and 3 English web-based electronic databases to evaluate the associations by odds ratio (OR) and its 95 % confidence interval (CI) under the recessive genetic comparison model (null genotype vs. present genotype). We also conducted subgroup analyses by ethnicity and adjusted status of OR, respectively. Meta-analyses and subgroup analyses of larger studies (sample size ≥300) were also reanalyzed. When 18 eligible studies (3,963 PD cases and 5,472 controls) were pooled to analyze the association, we found no statistically significant result (OR 1.24, 95 % CI 0.96–1.60). In the subgroup analyses by ethnicity, there was statistically significant association between the null genotype of GSTT1 and PD risk among Caucasians, while the associations were not found among Asians and Latinos. In the subgroup analyses by adjusted status of OR, there were no significant associations both in studies with crude OR and adjusted OR. Meta-analyses and subgroup analyses of larger studies (sample size ≥300) were also confirmed the associations mentioned above. Power analysis indicated only meta-analysis of Caucasians had enough evidence to claim the association. In conclusion, the meta-analysis suggests that the null genotype of GSTT1 contributes to PD risk in Caucasians, and no association in Asians is needed more studies to confirm.     

Polymorphisms in glutathione S-transferases in French vinyl chloride workers

The authors have recently demonstrated a significant gene–environment interaction between vinyl chloride exposure and polymorphisms in the DNA repair protein XRCC1 on the occurrence of mutant p53 biomarkers of vinyl chloride-induced genetic damage. The aim of this study was to examine the polymorphisms in the glutathione S-transferases (GSTs) as potential modifiers of this relationship, since these enzymes may be involved in the phase II metabolism of the reactive intermediates of vinyl chloride. A cohort of 211 French vinyl chloride workers was genotyped for common polymorphisms in GSTM1, GSTT1 and GSTP1. Although no independent, statistically significant effect of these polymorphisms on the occurrence of the mutant p53 biomarker was found, the null GSTM1 and null GSTT1 polymorphisms were found to interact with the XRCC1 polymorphism to increase the occurrence of the biomarker such that, for example, workers with at least one variant XRCC1 allele who were null for both GSTM1 and GSTT1 had a significant odds ratio for the biomarker (OR=8.4, 95% CI=1.3–54.0) compared with workers who were wild-type for all alleles, controlling for potential confounders including cumulative vinyl chloride exposure.     

GSTT1 null genotype contributes to coronary heart disease risk: a meta-analysis

Many studies have investigated the association between glutathione S-transferase T1 (GSTT1) null genotype and risk of coronary heart disease (CHD), but the impact of GSTT1 null genotype on CHD is still unclear owing to the obvious inconsistence among those studies. This study aims to quantify the strength of association between GSTT1 null genotype and risk of CHD. We searched the PubMed, Embase and Wangfang databases for studies relating the association between GSTT1 null genotype and risk of CHD. We estimated summary odds ratio (OR) with their 95 % confidence interval (95 % CI) to assess the association. 24 case-control studies with 13, 884 CHD cases and 30, 719 controls were included into this meta-analysis. Meta-analysis of total 24 studies showed GSTT1 null genotype was not associated risk of CHD (random-effects OR = 1.17, 95 % CI 0.97-1.42, P = 0.101). After adjustment for heterogeneity, meta-analysis showed GSTT1 null genotype was associated increased risk of CHD both in total population and Caucasians (for total population, fixed-effects OR = 1.12, 95 % CI 1.05-1.21, P = 0.001; for Caucasians, fixed-effects OR = 1.10, 95 % CI 1.02-1.19, P = 0.010). There was no significant association in the other populations. No evidence of publication bias was observed. Meta-analyses of available data suggest the GSTT1 null genotype contributes to increased risk of CHD in Caucasians.     

Glutathione S-transferase M1 and T1 gene polymorphism and COPD risk in smokers: an updated analysis

We evaluated the association between GSTM1 and GSTT1 gene polymorphisms and susceptibility to chronic obstructive pulmonary disease (COPD) in smokers. A meta-analysis of the published case–control studies was performed. Published literature was retrieved from PubMed, EMBASE, and China National Knowledge Infrastructure (CNKI), with last update in February, 2011. Data were extracted and a fixed- or random-effects model was used to calculate pooled odds ratios with 95% confidence intervals depending on statistical heterogeneity. Fourteen eligible studies, comprising 1,665 COPD cases and 1,614 controls, were included in the meta-analysis. The combined analyses showed that there was a significant difference in GSTM1 genotype distribution between COPD cases and controls among Caucasians, but not among Asians. The combined GSTM1/GSTT1 null genotype conferred a 1.36-fold greater risk for COPD in Asian smokers. The GSTT1 null genotype alone was not associated with enhanced risk for COPD. The GSTM1 null genotype is significantly associated with an increasing susceptibility to COPD in Caucasian smokers, but not in Asian smokers. The GSTM1/GSTT1 null genotype is a significant risk factor for developing COPD in Asian smokers. The GSTT1 null genotype, however, was not associated with COPD.     

A meta-analysis of the relationship between glutathione S-transferases gene polymorphism and hepatocellular carcinoma in Asian population

The results from the published studies on the association between glutathione S-transferases (GST) gene polymorphism and hepatocellular carcinoma (HCC) in Asian population are still conflicting. GSTM1, GSTT1 and GSTP1 are the mainly mutant sites reported at present. This meta-analysis was performed to evaluate the relationship between GST gene polymorphism and HCC risk in Asians. Association studies were identified from the databases of PubMed, Embase, Cochrane Library and CBM-disc (China Biological Medicine Database) on February 1, 2012, and eligible investigations were synthesized using meta-analysis method. Results were expressed with odds ratios (OR) for dichotomous data, and 95?% confidence intervals (CI) were also calculated. Twenty-five investigations were identified for the analysis of association between polymorphic deletion of GSTM1 and HCC, consisting of 3,547 patients with HCC and 6,132 controls. There was a marked association between GSTM1 null genotype and HCC susceptibility (OR 1.48, 95?% CI 1.19–1.85, P?=?0.0004). GSTM1 null genotype was associated with HCC risk in Chinese. Furthermore, null genotype of GSTT1 was associated with HCC susceptibility in Asians. For the GSTM1–GSTT1 interaction analysis, the dual null genotype of GSTM1/GSTT1 was significantly associated with HCC susceptibility in Asian population. However, GSTP1 ile105?val gene polymorphism was not associated with HCC risk in Asian population. In conclusion, GSTM1/GSTT1 null genotype is associated with the HCC susceptibility. However, GSTP1 gene polymorphism is not associated with HCC risk.     

Significant association between GSTT1 null genotype and susceptibility to pancreatic cancer

Many studies have investigated the association between glutathione S-transferase T1 (GSTT1) polymorphism and risk for pancreatic cancer, but those studies have yielded contradictory findings on the association. We performed a comprehensive search in the PubMed, EMBASE, and the Chinese National Knowledge Infrastructure databases to identify relevant studies. A meta-analysis was performed to examine the association between GSTT1 polymorphism and susceptibility to pancreatic cancer by calculating the pooled odds ratios (ORs) and corresponding 95 % confidence intervals (95 % CIs). Eight studies involving a total of 4,437 individuals were included. Overall, significantly increased pancreatic cancer risk was associated with GSTT1 null genotype when all studies were pooled into the meta-analysis (random effects OR = 1.61, 95 % CI 1.06–2.44; P = 0.025). Significantly increased risk of pancreatic cancer was also found for GSTT1 null genotype in Asians when stratified by ethnicity (fixed effects OR = 2.67, 95 % CI 1.74–4.09; P < 0.001). The findings demonstrate that GSTT1 null genotype have a modest effect on the genetic susceptibility to pancreatic cancer, and GSTT1 null genotype is associated with increased risk of pancreatic cancer.     

Polymorphisms in glutathione S-transferases in French vinyl chloride workers.

The authors have recently demonstrated a significant gene-environment interaction between vinyl chloride exposure and polymorphisms in the DNA repair protein XRCC1 on the occurrence of mutant p53 biomarkers of vinyl chloride-induced genetic damage. The aim of this study was to examine the polymorphisms in the glutathione S-transferases (GSTs) as potential modifiers of this relationship, since these enzymes may be involved in the phase II metabolism of the reactive intermediates of vinyl chloride. A cohort of 211 French vinyl chloride workers was genotyped for common polymorphisms in GSTM1, GSTT1 and GSTP1. Although no independent, statistically significant effect of these polymorphisms on the occurrence of the mutant p53 biomarker was found, the null GSTM1 and null GSTT1 polymorphisms were found to interact with the XRCC 1 polymorphism to increase the occurrence of the biomarker such that, for example, workers with at least one variant XRCC1 allele who were null for both GSTM1 and GSTT1 had a significant odds ratio for the biomarker (OR =8.4, 95% CI = 1.3 54.0) compared with workers who were wild-type for all alleles, controlling for potential confounders including cumulative vinyl chloride exposure.     

Genetic polymorphism of glutathione S-transferase T1 and the risk of colorectal cancer: A meta-analysis

Background: Studies investigating the association between genetic polymorphism of glutathione S-transferase T1 (GSTT1) and risk of colorectal cancer have reported conflicting results. In order to clarify the effect of GSTT1 polymorphism on the risk of developing colorectal cancer, we carried out a meta-analysis using published data to obtain more precise estimates of risk. Methods: Electronic searches of PubMed and EMBASE were conducted to select studies for this meta-analysis. Papers were included if they were observational studies investigating the association between GSTT1 polymorphism and colorectal cancer risk. The principal outcome measure was the odds ratio (OR) with 95% confidence interval (CI) for the risk of colorectal cancer associated with GSTT1 null genotype. Results: We identified 30 eligible studies, which included 7635 cases and 12,911 controls. The combined results based on all studies showed that there was a statistically significant link between GSTT1 null genotype and colorectal cancer risk (OR = 1.20, 95% CI = 1.03–1.40). In the analysis of ethnic groups, we observed distinct differences associated with GSTT1 null genotype, the pooled odds ratios for the GSTT1 polymorphism were 1.32 in Caucasians (95% CI = 1.09–1.58) and 1.03 in Asians (95% CI = 0.81–1.32). As far as concerned the interaction between GSTT1 genotype and colorectal cancer risk in relation to smoking history, there was no increase in risk for smokers or nonsmokers with the GSTT1 null genotype (smokers: OR = 1.13, 95% CI = 0.80–1.60, nonsmokers: OR = 0.99, 95% CI = 0.71–1.38). When stratifying by the location of colorectal cancer, we found that there was a statistically significant link in rectal cancer (OR = 1.50, 95% CI = 1.09–2.07), but not in colon cancer (OR = 1.33, 95% CI = 0.94–1.88). No associations could be detected between null GSTT1 polymorphism and age, sex, tumor stage and differentiation. Conclusion: Our current study demonstrates that GSTT1 null genotype is associated with an increased risk of colorectal cancer, specifically, among Caucasians.     

Significant association of glutathione S-transferase T1 null genotype with esophageal cancer risk: a meta-analysis

Recent studies on the association between glutathione S-transferase T1 (GSTT1) polymorphism and risk of esophageal cancer showed inconclusive results. To clarify this possible association, we conducted a meta-analysis of published studies. Data were collected from the following electronic databases: Pubmed, Embase, and Chinese Biomedical Database (CBM). The odds ratio (OR) and its 95 % confidence interval (95 % CI) was used to assess the strength of this association. We summarized the data on the association between GSTT1 null genotype and risk of esophageal cancer in the overall population, and performed subgroup analyses by ethnicity. Finally, a total of 24 independent studies including a total of 7,801 subjects (2,965 cases and 4,836 controls) were eligible for meta-analysis. In the overall analysis, there was no significant association between GSTT1 null genotype and esophageal cancer risk (OR = 1.15, 95 % CI 0.99–1.33, P = 0.067). However, meta-analysis of adjusted ORs showed a significant association between GSTT1 null genotype and increased risk of esophageal cancer (OR = 1.30, 95 % CI 1.08–1.56, P = 0.005). Subgroup analyses by ethnicity showed there was an obvious association between GSTT1 null genotype and increased risk of esophageal cancer in East Asians (OR = 1.24, 95 % CI 1.10–1.39, P < 0.001), but not in Caucasians (OR = 0.89, 95 % CI 0.71–1.11, P = 0.300). There was no obvious risk of publication bias in this meta-analysis (Egger’s test, P = 0.784). This meta-analysis demonstrates that GSTT1 null genotype is independently associated with increased risk of esophageal cancer, and a race-specific effect may exist in this association.     

Glutathione S-transferase T1 gene deletion polymorphism and lung cancer risk in Chinese population: A meta-analysis

Genetic variations in metabolic genes are considered to modulate metabolic process of carcinogens and are suggested to be related to cancer risk. However, epidemiological results are not always consistent. In this meta-analysis, we evaluated reported studies of association between polymorphism of glutathione S-transferase T1 gene (GSTT1) and the risk of lung cancer in Chinese population. We found an increased lung cancer risk among subjects carrying GSTT1 null genotype [odds ratio (OR) = 1.36, 95 percent confidence interval (95% CI): 1.09–1.69], using 1625 cases and 2188 controls from 11 studies. We also observed an increased risk of lung cancer among null genotype carriers in squamous cell carcinoma and andenocarcinoma, and on the basis of population control in stratified analyses. The meta-analysis suggests that GSTT1 deletion polymorphisms may have an effect on the susceptibility of lung cancer in Chinese population, and a study with the larger sample size is needed to further evaluate gene–gene and gene–environment interaction on GSTT1 deletion polymorphisms and lung cancer risk in Chinese population.     

Glutathione S-transferase T1 polymorphism contributes to bladder cancer risk: a meta-analysis involving 50 studies

Glutathione S-transferase T1 (GSTT1) is implicated in the inactivation of procarcinogens that contribute to cancer progression. However, studies investigating the association between GSTT1 polymorphism and bladder cancer (BC) risk have reported conflicting results; therefore, a meta-analysis was conducted. Fifty studies with 10,805 cases and 13,332 controls were recruited. The overall odds ratio for the GSTT1 null genotype was 1.1502 (95% CI=1.0384-1.2741). When stratified by ethnicity, significantly increased risk was only found for Caucasians. In Asians subgroup, interestingly, decreased BC risks were found in the Korean and Japanese populations but not in the Chinese population. When stratified by control sources, a slightly elevated risk was found in population-based but not in hospital-based studies. Besides, smoking was not found to modify the association between the GSTT1 null genotype and BC risk. When combined with the GSTM1 null genotype, a remarkably increased risk was found for BC. In general, our results suggest that the GSTT1 null genotype is associated with an increased risk of BC. Smoking did not modify the association between the GSTT1 null genotype and BC risk. Furthermore, a strong association was observed between the combination of GSTT1 null and GSTM1 null genotype and risk of BC. Further epidemiological studies will be needed to confirm our findings.     

Combined effect of prenatal solvent exposure and GSTT1 or GSTM1 polymorphisms in the risk of birth defects

Exposure to solvents during pregnancy has long been suspected to increase the risk of congenital malformations. Glutathione S-transferases (GSTs) are enzymes essential for the detoxification of various chemicals. Our objective here was to assess whether GST polymorphisms might modify the association between maternal solvent exposure and the risk of birth defects. A prospective cohort included 3421 pregnant women in Brittany, France (2002-2006). Occupational exposure to solvents was assessed from a job-exposure matrix. Congenital malformations were diagnosed among livebirths, stillbirths, and medical pregnancy terminations. Using a nested case-control design, 32 babies with major birth defects were compared to 348 normal births for babies' cord blood genotypes (at GSTT1 and GSTM1) and maternal occupational solvent exposure. Logistic models were used to adjust for potential confounders. The risk of major defects increased significantly in women with solvent exposure (20% of controls and 34% of cases). Frequencies of the null genotype of both the GSTT1 and GSTM1 genes were similar among controls and cases. There was a significantly increased risk of birth defects in GSTM1 not-null cord-blood genotype in pregnancies exposed to solvents (odds ratio [OR], 1.0 for not-null, not-exposed; OR, 4.0 for not-null, exposed; 95% confidence interval [CI], 1.4-11.2; OR, 1.6 for null, not-exposed; 95% CI, 0.6-3.9; OR, 1.0 for null, exposed; 95% CI, 0.2-4.7; p = 0.05). This nested case-control study suggests that the child's GSTM1 genotype modifies the risk of major birth defects among offspring of solvent-exposed women. Replication and additional investigations are necessary to confirm and elucidate these findings.     

Lung cancer risk in north Indian population: role of genetic polymorphisms and smoking

Lung cancer (LC) is the leading cause of cancer-related mortality in developing as well as developed countries. Life style choices, particularly tobacco smoking, have been implicated as the main cause in the development of the LC. Despite the fact that majority cases of the LC occur among smokers, only 1–15% of smokers develop LC. In the present study, we have explored the role of genetic polymorphism, smoking habit and their association to LC in a cohort of north Indian population. The polymorphic genes explored were CYP1A1, GSTM1, GSTP1 and GSTT1 using techniques of Polymerase chain reaction (PCR), Restriction Fragment Length Polymorphism (RFLP), Real Time PCR (RT PCR), and gene sequencing. Genetic polymorphism was analysed in 253 normal participants (control) and 93 LC patients originating from Lucknow, India. Data were compared using odds ratio and Fisher Exact Test. We found that smoking increases the susceptibility to LC threefold (OR = 2.9; 95% CI: 0.9–2.8). The most significant risk for LC (OR = 3.2; 95% CI: 0.7–3.8) was found in the association of the homozygous variant of CYP1A1 gene at A2455G base change at Exon 7 (Val/Val) genotype. There was a marginally significant association between LC and GSTT1 null genotype (OR = 1.3; 95% CI: 1.0–1.7) while no significant risk association was found between GSTP1 polymorphism and LC. The present study demonstrates that the presence of null genotype of GSTM1/GSTT1 taken together with CYP1A1 (Val/Val) genotype increases the susceptibility to LC eightfold in comparison to CYP1A1 (Ile/Ile) and GSTM1/ GSTT1 genotype.     

Influence of glutathione S-transferase polymorphisms (GSTT1, GSTM1, GSTP1) on type-2 diabetes mellitus (T2D) risk in an endogamous population from north India

Glutathione S-transferases (GSTs) belong to a group of multigene and multifunctional detoxification enzymes, which defend cells against a wide variety of toxic insults and oxidative stress. Oxidative stress leads to cellular dysfunction which contributes to the pathophysiology of diseases such as cancer, atherosclerosis, and diabetes mellitus. It is important to assess whether the glutathione S-Transferase (GSTT1, GSTM1 and GSTP1) genotypes are associated with type 2 diabetes mellitus as deletion polymorphisms have an impaired capability to counteract the oxidative stress which is a feature of diabetes. GSTT1, GSTM1 and GSTP1 gene polymorphisms were analysed in 321 patients and 309 healthy controls from an endogamous population from north India. An association analysis was carried out at two levels (a) individual genes and (b) their double and triple combinations. The proportion of GSTT1 and GSTM1 null genotypes was higher in diabetics compared to controls (GSTT1 30.8 vs. 21.0 %; GSTM1 49.5 vs. 27.2 %). The frequency of the null genotype at both loci was higher in diabetics (19.6 vs. 7.8 %) leading to an odds ratio of 2.90 (CI 1.76–4.78, P < 0.0001). At GSTP1locus, patients had a higher frequency of the V/V genotype (15.6 vs. 7.5 %) and significant susceptible odds ratio (2.56, CI 1.47–4.48, P < 0.001). A combination of null genotypes at GSTT1 and GSTM1 loci and V/V genotype of GSTP1 locus showed highest odds ratio (9.64, CI 1.53–60.63, P < 0.01). Overall this study highlights that GST genes may play an important role in the pathogenesis of type 2 diabetes. The risk is higher in individuals carrying more than one susceptible genotype at these loci. The potential role of GST polymorphisms as markers of susceptibility to type 2 diabetes needs further investigations in a larger number of patients and populations.     

Significant association between GSTT1 null genotype and risk of asthma during childhood in Caucasians

Asthma is a complex multifactorial disorder and its management requires a better understanding of its various pathogenesis and mechanisms. Previous studies assessing the association between glutathione S-transferase T1 (GSTT1) null genotype and asthma risk during childhood reported conflicting results. To get a more precise estimation of the association between GSTT1 null genotype and risk of asthma during childhood, we performed a meta-analysis of 16 studies with a total of 18,558 subjects. Subgroup analyses were performed by ethnicity. The pooled odds ratio (OR) with corresponding 95 % confidence interval (95 %CI) was used to assess the association. Overall, there was a significant association between GSTT1 null genotype and increased risk of children asthma (OR = 1.25, 95 % CI, 1.02–1.54; P = 0.032). Subgroup analyses showed GSTT1 null genotype was associated with increased risk of children asthma in Caucasians (OR = 1.46, 95 % CI, 1.04–2.03; P = 0.027), but not in Asians (OR = 1.03, 95 % CI, 0.55–1.94; P = 0.928) and Africans (OR = 1.33, 95 % CI, 0.92–1.91; P = 0.127). There was no evidence of publication bias in the subgroup analysis of Caucasians. In conclusion, there is a significant association between GSTT1 null genotype and risk of asthma during childhood in Caucasians. More well-designed epidemiological studies are needed to further assess this association in Asians and Africans.     

Germline polymorphisms of glutathione-S-transferase GSTM1, GSTT1 and p53 codon 72 in cervical carcinogenesis

The clinical significance of glutathione-S-transferase GSTM1, GSTT1 and p53 codon 72 polymorphisms in cervical carcinogenesis was investigated. Germline polymorphisms of GSTM1, GSTT1 and p53 codon 72 together with human papillomavirus (HPV) types were examined in a total of 457 blood and cervical smear samples from normal healthy women and the patients with premalignant and malignant cervical lesions. The 167 patients with low-grade squamous intraepithelial lesion (LSIL), 49 with high-grade SIL (HSIL) and 83 with squamous cell carcinoma (SCC) had significantly higher frequency of high-risk HPV than 158 controls. The 49 patients with HSIL and 83 with SCC had statistically higher frequency of null GSTT1 genotype than 158 controls. There was an increased odds ratio for null GSTT1 genotype in HSIL and SCC cases compared with controls among 191 patients with high-risk HPV. The 67 cases with HPV types 16 and/or 18 had higher frequency of the GSTT1 null genotype than 186 with other types of HPV. There was no statistical difference in the polymorphic frequency of GSTM1 and p53 codon 72 genotypes between SILs and controls with or without high-risk HPV. These results suggest that GSTT1 null genotype may increase the risk of cervical cancer particularly in the cases with high-risk HPV types in a Japanese population.     

Cytogenetic study of workers exposed to chromium compounds

The frequency of sister chromatid exchanges (SCEs), high SCE frequency cells (HFCs), and genetic polymorphism of genotypes glutathione S-transferase (GST) M1 and T1 were analyzed in peripheral lymphocytes of 35 workers occupationally exposed to chromium (Cr) and 35 matched control group. Results showed that workers exposed to Cr showed 6.07 SCE/cell, as compared to 4.76 SCE/cell for the control group (p<0.01). Smokers showed a statistically significant higher frequency of SCE than non-smokers in both groups. The work duration of Cr workers was an important factor. Workers exposed for more than 5 years showed a significantly higher level of SCEs (p<0.05). Workers exposed to Cr for 5 or more years had higher HFC rates (51.4%) than those exposed for less than 5 years (22.9%), with an odds ratio of 4.5 times than those exposed for less than 5 years. In HFC analysis, Cr workers who smoked showed a higher level of HFC (60%) than the control group (5.7%) and also had a higher odds ratio (60.4) compared with the control group. Among non-smokers, the odds ratio was 9.0. Another objective of this study is to investigate the relationship between SCE and genetic polymorphisms of GST M1 and T1 in Cr workers. The results showed that the incidence of GSTM1 null genotype was 60% in the control group and 77.1% in Cr workers, and percentages of GSTT1 deletion were 42.9% and 62.9% in control and exposed individuals, respectively. There was a slightly increased frequency of SCE among Cr workers with GSTM1 null genotype as opposed to non-null genotype individuals. A similar result was seen among the control group; however, there were no statistically significant differences. In conclusion, the current study found the positive induction of SCE in workers who smoked or/and were exposed to Cr. However, different GST genotypes did not influence the level of cytogenetic damage between groups. Despite slight variation in numbers, they all appear to be not different.     

Significant Association of Glutathione S-Transferase T1 Null Genotype with Prostate Cancer Risk: A Meta-Analysis of 26,393 Subjects

Background

Recent studies on the association between Glutathione S-transferase T1 (GSTT1) polymorphism and risk of prostate cancer showed inconclusive results. To clarify this possible association, we conducted a meta-analysis of published studies.

Methods

Data were collected from the following electronic databases: Pubmed, Embase, and Chinese Biomedical Database (CBM). The odds ratio (OR) and its 95% confidence interval (95%CI) was used to assess the strength of the association. We summarized the data on the association between GSTT1 null genotype and risk of prostate cancer in the overall population, and performed subgroup analyses by ethnicity, adjusted ORs, and types of controls.

Results

Ultimately, a total of 43 studies with a total of 26,393 subjects (9,934 cases and 16,459 controls) were eligible for meta-analysis. Overall, there was a significant association between GSTT1 null genotype and increased risk of prostate cancer (OR = 1.14, 95%CI 1.01–1.29, P = 0.034). Meta-analysis of adjusted ORs also showed a significant association between GSTT1 null genotype and increased risk of prostate cancer (OR = 1.34, 95%CI 1.09–1.64, P = 0.006). Similar results were found in the subgroup analyses by ethnicity and types of controls.

Conclusion

This meta-analysis demonstrates that GSTT1 null genotype is associated with prostate cancer susceptibility, and GSTT1 null genotype contributes to increased risk of prostate cancer.     

A meta-analysis of the relationship between glutathione S-transferase T1 null/presence gene polymorphism and the risk of lung cancer including 31802 subjects

The relationship between glutathione S-transferase T1 (GSTT1) null/presence gene polymorphism and the risk of lung cancer from the published reports are still conflicting. This study was conducted to evaluate the relationship between GSTT1 null/presence gene polymorphism and the risk of lung cancer using meta-analysis method. The association studies were identified from PubMed, and Cochrane Library on July 1, 2012, and eligible investigations were included and synthesized using meta-analysis method. 51 reports were recruited into this meta-analysis for the association of null genotype of GSTT1 with lung cancer susceptibility, consisting of 15,140 patients with lung cancer and 16,662 controls. There was a marked association between GSTT1 null genotype and lung cancer risk in overall populations (OR = 1.15, 95 % CI 1.04–1.27, P = 0.007). Furthermore, GSTT1 null genotype was associated with the lung cancer risk in Asians (OR = 1.47, 95 % CI 1.23–1.76, P < 0.0001). However, GSTT1 null genotype was not associated with the risk of lung cancer in Caucasians, Brazilian population and Africans. In conclusion, GSTT1 null genotype is associated with the lung cancer in overall populations and in Asians.