M1 Gene Polymorphisms Research Articles

Potential role of glutathione S‑transferase M1 gene polymorphism in kidney calcium oxalate stone formation.

The purpose of this study was to look into the effects of glutathione S-transferase M1 (GSTM1) gene polymorphism on the formation of kidney calcium oxalate stones. A total of 159 patients with kidney calcium oxalate stones were included in this study as a case group. One hundred and three healthy individuals were included in the control group. The age, gender, and levels of calcium (Ca), uric acid (UA), creatinine (Cr), and urinary creatinine (Ucr) are tracked. Peripheral blood samples are used to perform a polymerase chain reaction to identify the glutathione S-transferase (GST) gene polymorphism (PCR). A commercial kit was used in this study to measure the levels of malondialdehyde (MDA), nitric oxide (NO), total antioxidant capacity (T-AOC), and 8-hydroxydeoxyguanosine (8-OHdG) in peripheral blood. There was no difference in age or gender distribution between the case and control groups (P > 0.05). The Cr, Ucr, Ca, UA, 8-OHdG, MDA, NO, and T-AOC in the case group were significantly higher than those in the control group (P < 0.001). The Hardy-Weinberg genetic equilibrium test showed no difference between the case group (P = 0.23) and the control group (P = 0.09). In the case group, the 8-OHdG and NO in GSTM1 null genotype were significantly higher than those in GSTM1 genotype(P < 0.05), but there was no significant difference in MDA and T-AOC (P > 0.05). Multivariate regression analysis showed that the GSTM1 null genotype was positively correlated with 8-OHdG (P < 0.001) and NO (P < 0.001). GSTM1 gene polymorphism might be a detecting risk factor for kidney calcium oxalate stone formation. ChiCTR2100051300.

Relationship between glutathione S-transferase M1 gene polymorphism and gastric cancer

This experiment was designed to investigate the relationship between glutathione S-transferase M1 (GSTM1) gene polymorphism and gastric cancer (GC). For this purpose, from January 2013 to December 2014, 116 patients with GC diagnosed in the Department of Gastroenterology of our hospital and 120 healthy people in the physical examination center were selected as the research objects. 116 patients with GC served as the observation group and 120 healthy people in the physical examination center served as the control group. Collect and isolate the peripheral blood nucleated cells of the subjects, obtain the GSTM1 gene polymorphism by sequencing, analyze the differences of GSTM1 genotype between the two groups, compare the differences of clinicopathological characteristics of patients with different genotypes in the observation group, look for the survival relative risk factors of patients with GC, and analyze the risk factors of death risk of GC by multivariate Cox risk proportional regression. Results showed that the proportion of GSTM1 (-) in the observation group (62.07%) was raised compared with the control group (48.33%) (p<0.05). There was a correlation between GSTM1 gene polymorphism and smoking, TNM stage differentiation and GSTM1 gene polymorphism in the observation group. The specific analysis found that the proportion of non-smoking, stage I-III and low differentiation in the GSTM1 (-) group was raised compared with that in the GSTM1 (+) group (p<0.05). TNM stage, differentiation degree and GSTM1 gene polymorphism were correlated with the median survival time of patients with GC (p<0.05). Further multivariate Cox risk proportional regression analysis showed that TNM stage IV, low differentiation and GSTM1 (-) the relative risk coefficients of death in patients with GC were stage Ⅰ - Ⅲ, high/medium differentiation and GSTM1, respectively (+) patients were 1.75, 1.46, and 2.14 times higher. In conclusion, GSTM1 gene polymorphism is associated with susceptibility to GC, and the GSTM1 deletion genotype is an unfavourable factor for poor prognosis in patients with GC.

Association analysis of apoptosis-related gene caspase3, Integrin a subunit 1 and glutathione sulfur transferase M1 gene polymorphisms and susceptibility to gastric cardia carcinoma.

To explore the association of polymorphisms of apoptosis-linked genes caspase3 (CASP3), integrin a subunit 1 (ITGA1), glutathione sulfur transferase M1 (GSTM1) with susceptibility to gastric cardia carcinoma (GCC). From February 2016 to March 2018, selection of 113 GCC patients was as the gastric cancer (GC), and selection of 75 patients without gastric disease was as the control. Detection of CASP3, ITGA1 and GSTM1 gene polymorphisms in patients' peripheral blood was to analyze their association with GC. Division of the GC was into the good prognosis and the unpleasing prognosis in the light of the survival of patients after surgery of 3 years, and the predictable value of gene polymorphisms of CASP3, ITGA1 and GSTM1 in GCC patients was analyzed. CASP3 gene rs12108497 locus, ITGA1 gene rs1862610 locus and GSTM1 genotype of the GC and the control were in accord with Hardy-Weinberg equilibrium (P > 0.05); The detection rate of CASP3 gene rs12108497 locus TC/CC type, ITGA1's gene rs1862610 locus AC/AA type and GSTM1 blank type in the GC was elevated vs. the control (P < 0.05); Logistic regression analysis manifested smoking, anxiety, helicobacter pylori infection, family history of gastrointestinal tumor, combination with chronic gastric disease, CASP3 gene and GSTM1 gene polymorphism were risk factors for GC (P < 0.05); Stratification was in the light of individual smoking status, discovering that the detection rates of CASP3 gene rs12108497 locus TC/CC type, ITGA1 gene RS1862610 locus AC/AA type and GSTM1 blank type in the smoking were crucially augmented vs. the smoking (P < 0.05); The detection rates of CASP3 gene rs12108497 locus TC/CC type, ITGA1 gene rs1862610 locus AC/AA type and GSTM1 blank type in the death were augmented vs. the survival (P < 0.05); Combined detection of CASP3, ITGA1 and GSTM1 gene polymorphisms was provided with predictive value for GCC's prognosis (P < 0.05). CASP3 and GSTM1 genes are susceptibility genes for GCC, which might be associated with the occurrence of GCC in smoking patients, and the joint detection of multiple genes is provided with predictive value for patients' prognosis.

18S rRNA gene sequencing for environmental aflatoxigenic fungi and risk of hepatic carcinoma among exposed workers

Aspergillus exposure causes an increase in aflatoxin (AF) levels among exposed workers thereby increasing their risk of developing hepatocellular carcinoma (HCC). This study attempted to determine the presence of airborne aflatoxigenic fungi in environment of waste water treatment plant (WWTP); and study the hepatic cancer risks among exposed workers, emphasizing the role of glutathione S-transferases (GST) gene polymorphism protecting against the risk of hepatic cancer development due to exposure to AFs. The study isolated and identified different Aspergillus species producing AFs in air samples from WWTP sites using 18S ribosomal ribonucleic acid (18S rRNA) gene sequencing technique. GST gene polymorphisms were genotyped using polymerase chain reaction–restriction fragment length polymorphism (PCR-RFLP). A significant increase in blood AF levels was found among WWTP exposed workers. The occurrence of GSTT1& M1 gene polymorphism in 6% of the workers was accompanied by significant decrease in the levels of AFs and alpha fetoprotein (AFP). In conclusion, Aspergillus-producing AFs were found in air of WWTP. Continuous exposure to AF-producing fungi caused elevated AF-levels in exposed workers. However only workers with heterozygous GSTT1& M1 genotypes can detoxify AFs, thereby decreasing the risk of HCC development among exposed workers.

Glutathione S-Transferase T1 and M1 Gene Polymorphisms among Breast Cancer Susceptible Ghanaians

Background: Glutathione S-transferase (GST) gene polymorphism has been associated with breast cancer; however, there are conflicting results. Little or no information exists in the Ghanaian population. Aim: To determine the association between GST polymorphic genes (GSTM1 and GSTT1) and susceptibility to breast cancer in Ghanaian population. Method: 112 whole blood samples were retrieved from -80oC freezer. Samples comprised 56 female breast cancer patients. Demographic and clinical data were retrieved from records. Patients were age matched with 56 controls. Genomic DNA was extracted; GSTTI and GSTM1 genes amplified using multiplex PCR with appropriate primers and the resultant amplicons separated by agarose gel electrophoresis. Results: The prevalence of GSTT1 null in patients was 42.9% and with greater association with breast cancer (OR=2.84, 95% CI=1.52–5.29, p=0.001). The heterozygous GSTT1 null/GSTM1 genotype was strongly associated with breast cancer (OR=3.02, 95% CI=1.61–5.66, p 0.05). However, the presence of both genes was not a risk factor of breast cancer in the patients (OR=0.53, 95% CI=0.28–1.09, p=0.030). Conclusion: The GSTT1 null and GSTT1 null / GSTM1 genotypes may be potential risk factors for breast cancer susceptibility.

A meta-analysis of association between glutathione S-transferase M1 gene polymorphism and Parkinson's disease susceptibility.

The aim of this meta-analysis was to evaluate whether there was an association between glutathione S-transferase M1(GSTM1)gene polymorphism and Parkinson’s disease (PD) susceptibility by pooling published data.We performed comprehensive electronic database search for articles published between February12,2015 and April30 2016. The published case-control or cohort studies related to GSTM1 gene polymorphism and Parkinson’s disease susceptibility were screened, reviewed, and included in this meta-analysis. The correlation between GSTM1 gene polymorphism and PD susceptibility was expressed by odds ratio (OR) and its corresponding 95% confidence interval (95%CI). Publication bias was evaluated by Begg’s funnel plot and Egger’s line regression test. All analysis was done by stata11.0 software.After searching the PubMed, EMBASE, and CNKI databases, seventeen case-control studies with 3,538 PD and 5,180 controls were included in the final meta-analysis. The data was pooled by a fixed-effect model for lack of statistical heterogeneity across the studies; the results showed GSTM1 null expression can significant increase the susceptibility of PD (OR=1.11, 95% CI:1.01-1.21, P<0.05). Subgroup analysis indicated GSTM1 gene polymorphism was associated with PD susceptibility in the Caucasian ethnic group (OR=1.15, 95% CI:1.05-1.27, P<0.05) but not in the Asian ethnic group (OR=0.89, 95% CI:0.70-1.12, P>0.05). Begg’s funnel plot and Egger’s line regression test showed no significant publication bias.Based on the present evidence, GSTM1 null expression can significant increase the susceptibility of PD in persons of Caucasian ethnicity.

Glutathione S‐Transferase M1 Gene Polymorphism Is Associated with Susceptibility to Impaired Long‐term Allograft Outcomes in Renal Transplant Recipients

Despite improved post-transplantation care, progress in long-term kidney allograft survival of diabetic renal transplant recipients (pre-DM RTR) is worse than that of non-diabetic recipients (non-DM). We hypothesized that there are other potential risk factors, that predispose RTR to adverse renal allograft outcomes. A total of 323 transplant recipients who underwent renal transplantation between March 2000 and January 2008 were recruited. The composite end-point consisted of serum creatinine (SCr) doubling, graft failure, and death. Baseline clinical data were recorded, and polymerase chain reaction-restriction fragment length polymorphism measurements of interleukin (IL)-4, IL-10, IL-23, glutathione S-transferase (GST)A1, GSTM1, and GSTP1 polymorphisms were determined. The risk factors for developing the primary outcome were analyzed among these clinical and genetic factors. Within a mean follow-up of 71.1 ± 24 months, there were 43 (13.3 %) patients with the primary outcome. Stepwise multivariate Cox regression analysis was used to determine the risk factors for the primary outcome of RTR. Renal transplant recipients who possessed the GSTM1 null genotype had a 2.2-fold risk (95 % CI: 1.10-4.40; P = 0.026) of developing the primary outcome. Additionally, RTR that had DM before transplantation (aHR: 3.31; 95 % CI: 1.77-6.20; P = 0.0002) or changes in SCr 6 to 12 months after transplantation (aHR: 2.83; 95 % CI: 1.29-6.19; P = 0.0095) had an increased risk of developing the primary outcome. In addition to the adverse role played by DM, the GSTM1 null genotype also has an unfavorable influence on the long-term allograft outcome of RTR.

The association between glutathione S-transferase T1 and M1 gene polymorphisms and cardiovascular autonomic neuropathy in Slovak adolescents with type 1 diabetes mellitus

Glutathione S-transferase (GST), as antioxidant enzyme, protects tissue from oxidative damage typical for many pathologic conditions as type 1 diabetes (T1D) and its chronic complications. The aim of the study was to compare the prevalence of GST T1/M1 gene polymorphisms between diabetic adolescents with (CAN+) and without (CAN−) cardiovascular autonomic neuropathy. Forty-six subjects with T1D at the age 15–19years were enrolled. CAN was diagnosed in 19 patients (41.3%) based on standard cardiovascular tests. GST M1 null genotype was more prevalent in CAN+subjects but this was not statistically significant (OR=1.889, 0.61–6.55, p>0.05). GST T1 wild genotype nearly 5-fold increased the risk of CAN (OR=4.952, 1.13–21.739, p<0.05). Regarding genotype combination, GST T1/M1 wild/null genotype was significantly more frequent in CAN+compared to the CAN− subjects (OR=3.96, 1.024–15.302, p<0.05). No significant difference was found in any biochemical parameters between CAN+and CAN− subgroups. Multivariable logistic regression showed that none of the biochemical parameters estimated was considered a risk factor for CAN, however GST T1 wild and GST T1/M1 wild/null represented a risk factor for CAN development (OR=2.227, 1.079–4.587, p<0.05 and OR=1.990, 1.026–3.859, p<0.05, respectively). GST T1 wild allele and GST T1/M1 wild/null genotype can be considered as risk factors for CAN in Slovak adolescents with T1D.

Association of glutathione S-transferase T1 and M1 gene polymorphisms with ischemic stroke risk in the Chinese Han population.

Atherosclerosis plays an important role in ischemic stroke, and oxidative stress participates in the entire process of atherosclerosis. Glutathione S-transferase (GST) acting with other antioxidant enzymes can eliminate reactive oxygen species and protect cells against oxidative damage. To assess the association of glutathione S-transferase (GSTT1 and GSTM1) gene polymorphisms with ischemic stroke in the Chinese Han population, the present study selected 315 patients with ischemic stroke and 210 healthy controls for comparison. GSTT1 and GSTM1 genotypes were determined using polymerase chain reactions, electrophoresis and imaging analysis. No obvious evidence of GSTT1-null, GSTM1-null and GSTT1/GSTM1-double null genotype distribution differences was found between case and control groups or between genders. Subgroup analysis showed that the risk of stroke was increased when hypertension was accompanied by GSTT1-null (odds ratio (OR) = 2.996, P < 0.001) and GSTM1-null (OR = 3.680, P < 0.001) genotypes; diabetes mellitus was accompanied by GSTT1-null (OR = 1.860, P = 0.031) and GSTM1-null (OR = 2.444, P = 0.002) genotypes, and smokers showed a GSTT1-null genotype (OR = 2.276, P = 0.003). GSTT1- and GSTM1-null genotypes may interact synergistically with hypertension, diabetes mellitus and smoking to increase the incidence risk of ischemic stroke.

Association between methylene tetrahydrofolate reductase and glutathione S-transferase M1 gene polymorphisms and chronic myeloid leukemia in a Brazilian population

Chronic myeloid leukemia is a hematopoietic stem cell disorder that causes uncontrolled proliferation of white blood cells. Although the clinical and biological aspects are well documented, little is known about individual susceptibility to this disease. We conducted a case-control study analyzing the prevalence of the polymorphisms MTHFR C677T, MTHFR A1298C, del{GSTM1}, del{GSTT1}, and haptoglobin in 105 patients with chronic myeloid leukemia (CML) and 273 healthy controls, using PCR-based methods. A significant association with risk of developing CML was found for MTHFR 1298AA (odds ratio (OR) = 1.794; 95% confidence interval (CI) = 1.14-2.83) and GSTM1 non-null (OR = 1.649; 95%CI = 1.05-2.6) genotypes, while MTHFR 1298AC (OR = 0.630; 95%CI = 0.40-0.99) and GSTM1 null (OR = 0.606; 95%CI = 0.21-0.77) genotypes significantly decreased this risk. There appeared to be selection for heterozygosity at the MTHFR 1298 locus. The considerable range of variation in this and other human populations may be a consequence of distinctive processes of natural selection and adaptation to variable environmental conditions. The Brazilian population is very mixed and heterogeneous; we found these two loci to be associated with CML in this population.

Glutathione S-transferase M1 Gene Polymorphism and Gastric Cancer Risk: An Updated Analysis

Studies investigating the association between glutathione S-transferase M1 (GSTM1) gene polymorphism and gastric cancer (GC) risk have reported conflicting results. In order to clarify the effect of GSTM1 genotype on the GC risk, we performed an updated meta-analysis of published case-control and cohort studies to better compare results between studies. Published literature from PubMed, EMBASE, and China National Knowledge Infrastructure (CNKI) were retrieved, and the literature search was updated on June 15, 2010. 49 studies with 7746 cases of GC and 13,230 controls were selected. A fixed- or random-effects model was used to calculate pooled effect estimates depending on statistical heterogeneity. The combined analyses showed that there was a significant difference in genotype distribution between GC cases and controls among Asians, but not among Caucasians. Stratified analyses according to control sources also showed the positive association between GSTM1 null genotype and increased risk of GC. However, smoking and Helicobacter pylori infection did not modify the association between this polymorphism and GC susceptibility (p = 0.56 and 0.31, respectively). When stratifying by the location, Lauren's classification, and histological differentiation of GC, we observed no statistically significant differences in genotype distribution. A strong correlation between increased GC risk and the combined GSTM1 and GSTT1 null genotype was observed. This meta-analysis demonstrated that the GSTM1 gene polymorphism might be a risk factor for GC among Asians (especially, in some Eastern countries). Smoking, Helicobacter pylori infection status did not modify the association between GSTM1 null genotype and GC risk.

GST M1 Polymorphism Associates with DNA Oxidative Damage and Mortality among Hemodialysis Patients

Leukocyte 8-hydroxy-2'-deoxyguanosine (8-OHdG) is a surrogate marker of oxidant-induced DNA damage in patients undergoing maintenance hemodialysis (MHD). Glutathione S-transferase M1 (GST M1) is a member of the GST family of proteins, which protect cellular DNA against oxidative damage. This study tested the association of a common GST M1 gene polymorphism [GST M1(-)], known to produce a dysfunctional enzyme, with levels of 8-OHdG in peripheral blood leukocytes and all-cause mortality among MHD patients. Among 488 MHD patients and 372 gender-matched healthy subjects, the frequency of the GST M1(-) genotype was 63.1 and 60.2%, respectively. The GST M1(-) genotype was associated with significantly higher levels of leukocyte 8-OHdG compared with the GST M1(+) genotype, even after adjustment for potential confounders (P < 0.001). Moreover, GST M1(-) patients who also had a common polymorphism in the DNA repair enzyme 8-oxoguanine DNA glycosylase 1 or who underwent dialysis with a bioincompatible cellulose membrane had the highest median levels of leukocyte 8-OHdG. Multivariate Cox regression revealed that among MHD patients, GST M1(-) genotype approximately doubled the risk for all-cause mortality (hazard ratio 2.24; 95% confidence interval 1.30 to 4.51) during the mean follow-up of 34 mo. In conclusion, patients without GST M1 activity are more vulnerable to oxidative stress and are at greater risk for death compared with those who possess GST M1 activity.

Comparison of early enteral feeding versus parenteral nutrition after resection of esophageal cancer

expression of the human glutathione transferase active on trans-stilbene oxide are due to gene deletion. Proc Natl acad Sci U S A 1988;85:7293-7. [15] Zhong S, Wyllie AH, Barnes D, et al. Relationship between the GSTM1 genetic polymorphism and susceptibility to bladder, breast, and colon cancer. Carcinogenesis 1993;14:1821-4. [16] Fujita H, Narita T, Meguro H, et al. No association of glutathione S-transferase M1 gene polymorphism with diabetic nephropathy in Japanese type 2 diabetic patients. Nephrology 2000;22:479-86. [17] Lulufer T, Bahadir E, Ahmet C, et al. Glutathione S-transferase gene polymorphism as a susceptibility factor in smoking related coronary artery disease. Science 2004;99:223-9.

Glutathione‐S‐transferase T1 and M1 gene polymorphisms in Greek patients with multiple sclerosis: a pilot study

Oxidative stress has been implicated in the pathogenesis of multiple sclerosis (MS). Glutathione-S-transferases (GSTs) are detoxification enzymes, evolved to protect cells against reactive oxygen metabolites. Both GSTT1 and GSTM1 genes exhibit a homozygous deletion polymorphism (null genotype) leading to abolished enzyme activity. We studied the impact of the GSTT1 and GSTM1 polymorphisms on MS susceptibility in a case-control study of 47 Greek patients and 165 controls. Correlations between genotype, gender and disability status were also investigated. The incidence of both GSTT1 and GSTM1 genotypes did not differ significantly between controls and patients. A significantly increased frequency of GSTM1 null genotype was found amongst female patients (65.5%) as compared with males (33.3%, P =0.04). The results suggest that GSTT1 and GSTM1 have no major pathogenetic role on the MS occurrence, nor any strong modifying effect on the disability status. The higher incidence of GSTM1 null genotype observed in female patients, suggests a possible role of the GSTM1 detoxification pathway in a gender-dependent manner.

Different susceptibility to peroxisome proliferator‐induced hepatocarcinogenesis in rats with polymorphic glutathione transferase genes

Although peroxisomal bifunctional enzyme (enoyl-CoA hydratase/L-3-hydroxyacyl-CoA dehydrogenase; BE) is a positive marker for peroxisome proliferation, it is completely absent or expressed very weakly in rat hepatic preneoplastic and neoplastic lesions induced by peroxisome proliferators (PP). After administration of PP for 8-15 weeks, some rats exhibit BE-negative preneoplastic foci but other rats do not. In the present study, to investigate the involvement of glutathione S-transferase (GST) M1 gene polymorphism in interindividual differences in susceptibility to PP, we developed a method to determine the genotypes of rats. We then examined whether rats with one type encoding 198Asn-199Cys (NC-type) or another encoding 198Lys-199Ser (KS-type) exhibit differences in clofibrate (CF) susceptibility. After administration of 0.3% CF for 6 weeks or more, BE-negative foci were found immunohistochemically in KS/KS-type rats, but not in NC/NC-type rats. The number of BE-negative foci in KS/KS rats was 15.3 +/- 9.0 foci/cm2 of liver section after 6 weeks of CF administration, and the values did not alter thereafter. The mean areas of BE-negative foci in KS/KS rat livers increased during the period from 6 to 60 weeks. At weeks 30 and 60, almost all BE-negative foci exhibited a clear cell phenotype, a type of preneoplastic hepatic lesion. BE-negative foci were devoid of peroxisome proliferator-activated receptor alpha, whereas surrounding tissues were positive for the receptor. These results indicate that rats that are polymorphic for the GST M1 gene exhibit different susceptibilities to CF in vivo.

Glutathione S-Transferase M1 Gene Polymorphisms are Associated with Cardiac Iron Deposition in Patients with β-Thalassemia Major

Patients with β-thalassemia (thal) major are subject to peroxidative tissue injury by iron overload. Glutathione S-transferases work as antioxidants, and their activity is determined genetically. In this study, we used multiplex polymerase chain reaction (m-PCR) to analyze polymorphisms of two endogenous antioxidant agents, glutathione S-transferase M1 (GSTM1) and glutathione S-transferase T1 (GSTT1), and to determine their roles in 41 patients with β-thal major. Our results showed that the GSTM1 and GSTT1 null genotypes were not associated with any incidence of endocrine dysfunction (including diabetes mellitus, hypogonadism, hypothyroidism, and growth hormone deficiency), liver function, or impaired left ventricular ejection fraction (LVEF). The GSTM1 null genotype, but not the GSTT1 null genotype, was associated with a decreased signal intensity ratio on cardiac magnetic resonance imaging (MRI). Our results suggest that genetic variations of the GSTM1 enzyme are associated with cardiac iron deposition in patients with β-thal major.

Glutathione S-transferase M1 gene polymorphism is related to COPD in patients with non-small-cell lung cancer.

Oxidative stress contributes to the development of both lung cancer and chronic obstructive pulmonary disease (COPD). Antioxidative enzymes may protect against such damage. We hypothesized that genetic variations in glutathione S-transferase M1 and/or T1 genes (GSTM1 and GSTT1, respectively) may influence susceptibility to COPD in patients with non-small-cell lung cancer. The polymorphisms in GSTM1 and GSTT1 genes were examined in 110 patients (age: 63+/-1 years) with newly diagnosed non-small-cell lung cancer using the polymerase chain reaction. Respiratory function was assessed by bodyplethysmography. In the GSTM1 null (-/-) genotype, both FEV1 and FEV1/FVC were significantly lower than in the GSTM1 plus genotype (GSTM1 -/+ or +/+) (75.8+/-2.5 versus 86.6+/-3.6%, p<0.02; 69.1+/-1.6 versus 77.0+/-2.4, p<0.01, respectively). Among the patients with GSTM1 null genotype, 49% suffered from COPD as opposed to 21% of patients with GSTM1 plus genotype. In contrast, no differences were seen in FEV1 or FEV1/FVC when comparing patients with GSTT1 null genotype and GSTT1 plus genotype (81.4+/-4.9 versus 79.3+/-2.3, p=NS; 71.1+/-2.9 versus 72.2+/-1.6, p=NS). Multiple stepwise regression analysis identified the GSTM1 genotype (p<0.02) as a significant independent predictor of FEV1 in this group of patients. The present study suggests that in patients with non-small-cell lung cancer the presence of at least one active allele in GSTM1 has a protective effect against the development of COPD.

Glutathione S-transferase M1 gene polymorphism in bladder cancer patients: a marker for invasive bladder cancer?

The glutathione S-transferase M1 ( GSTM1) gene is polymorphic in humans, and the deficiency in enzyme activity of GSTM1 is caused by the inherited homozygous absence of the GSTM1 gene, or the “null” genotype ( GSTM1, 0/0). The increased risk of bladder cancer has been shown to correspond with this gene defect. No reports, however, have been found in the literature regarding GSTM1 gene deficiency with superficial and invasive bladder cancer. In this study, we examined the association of the GSTM1-null genotype with superficial and invasive bladder cancer. Using a polymerase chain reaction (PCR)-based method, we examined the frequency of the GSTM1 gene defect in Turkish patients with superficial bladder cancer ( N = 61), invasive bladder cancer ( N = 42), and control subjects ( N = 202) who had no history of cancer. The GSTM1 null genotype was observed in 34.7% of the control subjects and in 54.3% of total bladder cancer patients (OR: 2.246; 95% CI: 1.384–3.645, P: 0.00094). In other words, the presence of the GSTM1-null genotype significantly increased the risk of bladder cancer development. Among invasive bladder cancers, the frequency of the GSTM1-null genotype was 64.3% (OR: 0.294, 95% CI: 0.147–0.590, P: 0.0003). This was also significantly higher than control subjects, indicating that patients carrying this genotype were at increased risk for developing invasive bladder cancer. This relationship was not statistically significant in the superficial bladder cancer group (OR: 0.585, 95% CI: 0.327–1.045, P: 0.06). Our results indicate that GSTM1 gene polymorphism should be considered as an important risk modifier in the development of bladder cancer and might be used as a predictive marker for invasive bladder cancer.

RELATIONSHIP BETWEEN GLUTATHIONE S-TRANSFERASE M1 DEFICIENCY AND UROTHELIAL CANCER IN DYE WORKERS EXPOSED TO AROMATIC AMINES

Purpose It is speculated that the susceptibility to urothelial cancer in dye workers who are exposed to aromatic amines is affected not only by occupational environmental factors but by host specific factors. We evaluated the interaction between glutathione S-transferase M1 gene deficiency and the occupational environmental factors associated with urothelial cancer. Materials and Methods The study included 137 workers who had prior exposure to dyestuff intermediates, of whom 36 had urothelial cancer. The prevalence of a glutathione S-transferase M1 gene polymorphism was investigated using polymerase chain reaction. The relationship between the glutathione S-transferase M1 0/0 gene and occupational environmental factors in the onset of urothelial cancer was examined by multivariate analysis. Results The prevalence of glutathione S-transferase M1 gene deficiency did not differ significantly between the urothelial cancer (21 cases, 58.3%) group and the cancer-free (47, 46.3%) group. It was estimated that 29.6% of the urothelial cancers in these dye workers was attributable to the glutathione S-transferase M1 0/0 gene. Analysis using multiple logistic models showed low predictive ability for urothelial cancer due to glutathione S-transferase M1 gene deficiency (p = 0.084, odds ratio 2.260, 95% confidence interval [CI] 0.904 to 5.652). A history of working in small factories (p = 0.000, odds ratio 7.404, 95% CI 2.854 to 19.206) and a long period of exposure (p = 0.016, odds ratio 5.051, 95% CI 1.371 to 18.612) significantly predicted cancer. Conclusions We demonstrated a strong trend using the multiple logistic analysis of the contribution of glutathione S-transferase M1 gene polymorphism and occupational environmental factors. Therefore, the glutathione S-transferase M1 enzyme might have an important role in the detoxification of aromatic amine derived carcinogens. Occupational environmental factors, however, might contribute more than a glutathione S-transferase M1 gene deficiency to the occurrence of urothelial cancer among individuals exposed to aromatic amines, because of the extremely potent carcinogenecity of some occupational environmental factors.