Glutathione-S-transferase （GSTM1, GSTrl） and the risk of gastrointestinal cancer in a Korean population

AIM: To evaluate the association of glutathione S-transferase mu (GSTM1) and glutathione S-transferase theta (GSTT1) null genotypes with the risk of gastric cancer (GC) and colorectal cancer (CRC) in a South Korean population.METHODS: We conducted a population-based, large-scale case-control study including 2213 GCs, 1829 CRCs, and 1699 controls. Null and non-null genotypes of GSTM1 and GSTT1 were determined using real-time PCR.RESULTS: The null genotypes of GSTM1 and GSTT1 were not significantly associated with elevated risk of gastric (OR = 1.070, 95% CI = 0.935-1.224; OR = 1.101, 95% CI = 0.963-1.259, respectively) or colorectal cancer (OR = 1.065, 95% CI = 0.923-1.228; OR = 1.041, 95% CI = 0.903-1.200, respectively). The frequency of the combined null GST genotype was not different between the two cancer groups and controls. Moreover, smoking, drinking, and age did not modify the association between these genotypes and the risk of gastric or colorectal cancer.CONCLUSION: GSTM1 and GSTT1 null genotypes were not associated with increased risk of GC or CRC in Koreans.     

Glutathione-S-transferase gene polymorphisms (GSTT1, GSTM1, GSTP1) as increased risk factors for asthma

OBJECTIVES: Asthma is a complex multifactorial disease with an obvious genetic predisposition, immunological aberration, and involvement of noxious environmental factors. Polymorphisms of the glutathione-S-transferase (GST) genes are known risk factors for some environmentally-related diseases. In the present study, the hypothesis that polymorphisms in the GSTT1, GSTM1 and GSTP1 genes are associated with atopic and nonatopic asthma was examined. METHODOLOGY: The study population consisted of 103 unrelated healthy individuals and 101 patients with bronchial asthma (64 atopic, 37 nonatopic). Asthma was diagnosed according to the American Thoracic Society statement. Genotyping of polymorphisms in the GSTT1, GSTM1 and GSTP1 genes was performed using real time polymerase chain reaction with a Light Cycler instrument and hybridization probes in combination with the Light Cycler DNA master hybridization probes kit. RESULTS: Patients with atopic asthma (34.4%) had a higher prevalence of the GSTT1 null genotype than the nonatopic asthma patients (13.5%; OR = 3.83; 95% CI, 1.24-11.78). Asthma patients (63.4%) had a higher prevalence of the GSTM1 null genotype than the control group (40.8%; OR = 2.34; 95% CI, 1.31-4.20). Subjects with the GSTP1 homozygous Val/Val genotype had a 3.55-fold increased risk of having atopic asthma compared to nonatopic asthma (OR = 3.55; 95% CI, 1.10-12.56). CONCLUSIONS: These results suggest that the GSTT1 and GSTM1 null genotypes and the GSTP1 Val/Val polymorphism may play important roles in asthma pathogenesis. It is possible that intermediate electrophilic metabolites, arising in the first phase of detoxification, are not metabolized by GST enzymes in asthmatic patients and are not excreted. These intermediate metabolites may damage cells and generate oxidative stress, and so contribute to the pathogenesis of asthma.     

Polymorphism of glutathione S-transferase mu 1 and theta 1 genes and hepatocellular carcinoma in southern Guangxi, China

AIM: Glutathione S-transferase mu 1 (GSTM1) and theta 1 (GSTT1) genes are involved in the metabolism of a wide range of carcinogens, but deletions of the genes are commonly found in the population. The present study was undertaken to evaluate the association between GSTM1 and GSTT1 gene polymorphisms and hepatocellular carcinoma (HCC) risk. METHODS: The genetic polymorphisms were studied at an aflatoxin highly contaminated region in Guangxi, China. Pdymerase chain reaction (PCR) technique was used to detect the presence or absence of the GSTM1 and GSTT1 genes in blood samples. The case group was composed of 181 patients of HCC identified by the pathologists and the control group was composed of 360 adults without any tumor. RESULTS: The frequencies of GSTM1 and GSTT1 null genotypes in the control were 47.8% and 42.7%, while those in the HCC group were 64.6% and 59.7%, respectively. The differences between HCC group and control group were very significant (P<0.01). GSTM1 and GSTT1 combined null genotypes in HCC group and control group were 38.2% and 18.5% respectively, and the difference was significant (P<0.05). CONCLUSION: The GSTM1 and GSTT1 null genotypes are associated with an increased risk of HCC in a special geographic environment. Combination of the two null genotypes in an individual is substantially increased twice the risk of HCC.     

Effect of dietary vitamin C on gastric cancer risk in the Korean population

AIM: To investigate the effects of dietary vitamin C and foods containing vitamin C on gastric cancer risk.METHODS: Our study included 830 control subjects and 415 patients. Data regarding demographics, medical history, and lifestyle, including dietary and nutrient intake, were collected using reliable selfadministered questionnaires. Dietary intake information was collected from the participants using a food frequency questionnaire that has been previously reported as reliable and valid. A rapid urease test and a histological evaluation were used to determine the presence of Helicobacter pylori(H. pylori) infection. Twenty-three vitamin C-contributing foods were selected, representing over 80% of the cumulative vitamin C contribution. RESULTS: In analyses adjusted for first-degree family history of gastric cancer, education level, job, household income, smoking status, and regular exercise, an inverseassociation between vitamin C intake and gastric cancer risk was observed for the highest(≥ 120.67 mg/d) vs the lowest( 80.14 mg/d) intake category [OR(95%CI): 0.64(0.46-0.88)], with a significant trend across the three intake categories(P = 0.007). No protective effect of vitamin C was detected after stratification by gender. No effect of vitamin C intake on the gastric cancer incidence was found in either men or women infected with H. pylori. Vitamin C-contributing foods, including cabbage [0.45(0.32-0.63), 0.50(0.34-0.75), 0.45(0.25-0.81)], strawberries [0.56(0.40-0.78), 0.49(0.32-0.74), 0.52(0.29-0.93)], and bananas [0.40(0.29-0.57), 0.41(0.27-0.62), 0.34(0.19-0.63)], were protective factors against the risk of gastric cancer based on the results of the overall adjusted analyses and the results for men and women, respectively.CONCLUSION: A protective effect of vitamin C and vitamin C-contributing foods against gastric cancer was observed. Further studies using larger sample sizes are required to replicate our results.     

新疆哈萨克族人群谷胱甘肽S转移酶M1、T1基因多态性

目的 探讨谷胱甘肽S转移酶M1、T1基因多态性在新疆哈萨克族人群中分布的特点.方法通过多重聚合酶链反应对新疆哈萨克族264例个体 GSTM1、GSTT1基因型进行检测.结果 GSTM1、GSTT1基因缺失型在新疆哈萨克族人群中频率分别为47%及36.4%,同时为GSTM1、GSTT1基因缺失型的频率为20.5%.结论 新疆哈萨克族人群GSTM1、GSTT1基因多态性与汉族及其他少数民族存在一定差异.     

GSTM1基因多态性与中国汉族人群肺癌易感性的Meta分析

目的 探索谷胱甘肽硫转移酶M1(GSTM1)基因多态性与中国汉族人群肺癌发生的相关性.方法 检索2011年8月之前GSTM1基因多态性与肺癌相关性的相关文献,根据纳入、排除标准选择符合要求的文献,整理GSTM1功能型基因型、缺失型基因型频数或频率,采用Mantel-Haenszel固定效应模型分析合并OR值,并用漏斗图和Egger线性回归分析评估文献的发表偏倚.结果 GSTM1(-)基因型携带者发生肺癌的风险是GSTM1(+)基因型携带者的1.64倍(95％CI:1.43～1.87),有统计学意义(Z=7.19,P＜0.01);发表偏倚的漏斗图对称,Egger线性回归分析回归截距为-0.422(95％CI:-3.011～2.167),无发表偏倚(P=0.734).结论 GSTM1基因是肺癌发生的易感基因,其中GSTM1缺失型基因型是中国汉族人群发生肺癌的风险因子.     

Polymorphisms of the glutathione S-transferases mu-1 (GSTM1) and theta-1 (GSTT1) and the risk of advanced alcoholic liver disease

Objective. The aim of this study was to determine whether null genotypes for glutathione transferase mu-1 (GSTM1) and theta-1 (GSTT1) influence the risk of development of advanced alcoholic liver disease. Material and methods. GSTM1 and GSTT1 genotypes were identified on DNA through multiple analysis with polymerase chain reaction in 153 subjects diagnosed with advanced alcoholic liver disease and in 241 healthy controls. Results. The frequency of the GSTM1 null genotype was not different between patients and controls (36.6% versus 41.1%, non-significant). The GSTT1 null genotype was more frequently found in patients than in controls (32% versus 22%, odds ratio 1.67, 95% CI 1.03–2.71, p=0.027). Moreover, patients were more likely to be simultaneous carriers of both GSTM1 and GSTT1 null genotypes (odds ratio 4.30, 95% CI 1.89–9.97, p=0.0003). Conclusions. The GSTT1 null genotype is more frequent among patients with advanced alcoholic liver disease than in controls. The coincidence of this genotype with the GSTM1 null genotype is four times more likely in patients. We suggest that polymorphisms affecting the activity of the glutathione S-transferase isoforms M1 and T1 may be associated with the risk of developing chronic severe ethanol liver damage.     

Family history of gastric cancer is associated with the risk of colorectal neoplasia in Korean population

BackgroundFamily history of cancers at different sites except for colorectum has not been evaluated as a risk factor for colorectal neoplasia (CRN).AimsTo investigate CRN risk according to family history of cancers at 12 different sites, including stomach and colorectum.MethodsA cross-sectional study was performed on 139,497 asymptomatic Koreans who underwent colonoscopy as part of a health check-up.ResultsThe mean age of the study population was 41.6 and the prevalence of CRN was 16.3%. Multivariate analyses revealed that family histories of CRC (adjusted odds ratio; confidence interval, 1.26; 1.17–1.35) and gastric cancer (1.07; 1.01–1.13) were independent risk factors for CRN. Notably, the risk of CRN increased even more for participants with family histories of both CRC and gastric cancer (1.38; 1.12–1.70). Family history of CRC was associated with risk of CRN in participants aged both <50 and ≥50 years, whereas family history of gastric cancer was associated with risk of CRN in participants aged <50 years (1.22; 1.14–1.30), but not in participants aged ≥50 years (1.08; 0.99–1.18).ConclusionsFamily history of gastric cancer was an independent risk factor for CRN, especially in those aged <50 years. Persons with family histories of gastric cancer and CRC, especially those with family histories of both, may need to begin colonoscopy earlier.     

Vegetable／fruit, smoking, glutathione S-transferase polymorphisms and risk for colorectal cancer in Taiwan

AIM: To investigate the colorectal cancer risk associated with polymorphic GSTM1, GSTT1 and GSTP1 and the effect of diet and smoking. METHODS: With consents, genotypes of the genes were determined using PCR methods for 727 cases and 736 sex and age-matched healthy controls recruited at a medical center in the Northern Taiwan. Nurses who were blind to the study hypothesis conducted interviews with study participants for the information of socio-demographic variables, diet and smoking. RESULTS: There was no significant association between GSTM1 genotypes and the disease. Men, not women, with GSTT1 null genotype were at significant risk of colorectal cancer, but limited to rectal tumor, and in men aged 60 years and less. The corresponding association with the GSTP1 with G allele compared to GSTP1 A/A genotype was at borderline significance. Compared to men with GSTT1 present and GSTP1 A/A combined, men with both GSTT1 null and GSTP1 with G allele genotypes were at significant risk (odds ratio (OR) = 1.91, 95% confidence interval (CI) = 1.21-3.02), also limited to the rectal tumor and younger men. The beneficial effects of vegetable/fruit intake on colorectal cancer were much higher for men with GSTT1 present (OR = 0.32, 95%CI = 0.20-0.50) or GSTP1 A/A genotypes (OR = 0.40, 95%CI = 0.25-0.64). These effects remained significant for women. But, the greatest protective effect from vegetable/fruit intake for women was observed in those with GSTT1 null or GSTP1 with G allele genotypes. In addition, non-smoking men benefitted significantly from combined effect of higher vegetable/fruit intake and GSTT1 present or GSTP1 A/A genotypes with OR=0.17 and 0.21 respectively. CONCLUSION: This study suggests that the GSTT1 gene can modulate the colorectal cancer risk and vegetable/ fruit-related colorectal cancer risk, particularly in men of no smoking history.     

Relation between glutathione S-transferase genes (GSTM1, GSTT1, and GSTP1) polymorphisms and clinical manifestations of sickle cell disease in Egyptian patients

Abstract

Objectives

Clinical manifestations of sickle cell disease (SCD) result from sickling of Hb S due to oxidation, which is augmented by accumulation of oxygen-free radicals. Deficiencies in normal antioxidant protective mechanism might lead to clinical manifestations of SCD like vaso-occlusive crisis (VOC) and acute chest syndrome (ACS). The glutathione system plays an important role in the removal of endogenous products of peroxidation of lipids, thus protecting cells and tissue against damage from oxidative stress. Impairment of the glutathione system due to genetic polymorphisms of glutathione S-transferase (GST) genes is expected to increase the severity of SCD manifestations. This report describes a case control study aimed at studying the ethnic-dependent variation in the frequency of GST gene polymorphisms among participants selected from the Egyptian population and to find out the association between GST gene polymorphisms and the severity of SCD manifestations.

Methods

We measured the frequency distribution of the three GSTs gene polymorphisms in 100 Egyptian adult SCD patients and 80 corresponding controls. GSTM1 and GSTT1 genotypes were determined by multiplex polymerase chain reaction (PCR). GSTP1 genotyping was conducted with a PCR-restriction fragment length polymorphism assay.

Results

The GSTM1 null genotype was significantly associated with ACS and VOC (P = 0.03 and 0.01, respectively). The GSTT1 null genotype was associated with significantly increased requirement of blood transfusion (P = 0.01). Absence of both GSTM1 and GSTT1 genes was significantly associated with pulmonary hypertension (P = 0.04). The non-wild-type GSTP1 polymorphism was not associated with clinical manifestations of SCD.

Discussion

Some GST gene polymorphisms were significantly associated with the worsening of the clinical manifestations of SCD.     

Increased risk for acute myeloid leukaemia in individuals with glutathione S-transferase mu 1 (GSTM1) and theta 1 (GSTT1) gene defects

OBJECTIVES: Glutathione S-transferases (GST) modulate the effects of exposure to various cytotoxic and genotoxic agents, including those associated with increased risks of the myelodysplastic syndrome (MDS), acute myeloid leukaemia (AML) and aplastic anemia (AA). Both the GST mu 1 (GSTM1) and GST theta 1 (GSTT1) genes have a null variant allele in which the entire gene is absent. In this study, we tested whether null genotypes for the GSTM1 and GSTT1 genes altered the risks for MDS, AML and AA. METHODS: Genomic DNA from 49 MDS, 38 AML and 37 AA patients and 276 controls was analysed using the polymerase chain reaction (PCR). RESULTS: The frequencies of GSTM1 (73.6%) and GSTT1 (34.2%) null genotypes were significantly higher in AML patients than in the controls (36.9 and 18.1%, respectively). A higher frequency of the combined null genotype for both genes was also observed in patients with AML (26.3% compared with 5.0% in the controls). In contrast, no differences in the frequencies of the null genotypes were found among MDS patients, AA patients and the controls. CONCLUSION: Our observation of a 4.7-fold (95% CI: 2.1-11.0) and 2.3-fold (95% CI: 1.0-5.2) increased risk associated with the GSTM1 and GSTT1 null genotypes, respectively, and a 6.6-fold (95% CI: 2.4-7.9) increased risk associated with the combined null genotype presents preliminary evidence that the inherited absence of this carcinogen detoxification pathway may be an important determinant of AML.     

Impact of SNP-SNP interactions of DNA repair gene ERCC5 and metabolic gene GSTP1 on gastric cancer/atrophic gastritis risk in a Chinese population

AIM To investigate the interactions of the DNA repair gene excision repair cross complementing group 5(ERCC5) and the metabolic gene glutathione S-transferase pi 1(GSTP1) and their effects on atrophic gastritis(AG) and gastric cancer(GC) risk.METHODS Seven ERCC5 single nucleotide polymorphisms(SNPs)(rs1047768, rs2094258, rs2228959, rs4150291, rs4150383, rs751402, and rs873601) and GSTP1 SNP rs1695 were detected using the Sequenom MassA RRAY platform in 450 GC patients, 634 AG cases, and 621 healthy control subjects in a Chinese population.RESULTS Two pairwise combinations(ERCC5 rs2094258 and rs873601 with GSTP1 rs1695) influenced AG risk(P_(interaction) = 0.008 and 0.043, respectively), and the ERCC5 rs2094258-GSTP1 rs1695 SNP pair demonstrated an antagonistic effect, while ERCC5 rs873601-GSTP1 rs1695 showed a synergistic effect on AG risk OR = 0.51 and 1.79, respectively). No pairwise combinations were observed in relation to GC risk. There were no cumulative effects among the pairwise interactions(ERCC5 rs2094258 and rs873601 with GSTP1 rs1695) on AG susceptibility(P_(trend) 0.05). When the modification effect of Helicobacter pylori(H. pylori) infection was evaluated, the cumulative effect of one of the aforementioned pairwise interactions(ERCC5 rs873601-GSTP1 rs1695) was associated with an increased AG risk in the case of negative H. pylori status(P_(trend)= 0.043).CONCLUSION There is a multifarious interaction between the DNA repair gene ERCC5 SNPs(rs2094258 and rs873601) and the metabolic gene GSTP1 rs1695, which may form the basis for various inter-individual susceptibilities to AG.     

ITGA1 polymorphisms and haplotypes are associated with gastric cancer risk in a Korean population

AIM:To evaluate the association between the geneticpolymorphisms and haplotypes of the ITGA1 gene and the risk of gastric cancer.METHODS:The study subjects were 477 age-and sex-matched case-control pairs.Genotyping was performed for 15 single nucleotide polymorphisms(SNPs)in ITGA1.The associations between gastric cancer and these SNPs and haplotypes were analyzed with multivariate conditional logistic regression models.Multiple testing corrections were carried out following methodology for controlling the false discovery rate.Gene-based association tests were performed using the versatile gene-based association study(VEGAS)method.RESULTS:In the codominant model,the ORs for SNPs rs2432143(1.517;95%CI:1.144-2.011)and rs2447867(1.258;95%CI:1.051-1.505)were statistically significant.In the dominant model,polymorphisms of rs1862610 and rs2447867 were found to be significant risk factors,with ORs of 1.337(95%CI:1.029-1.737)and 1.412(95%CI:1.061-1.881),respectively.In the recessive model,only the rs2432143 polymorphism was significant(OR=1.559,95%CI:1.150-2.114).The C-C type of ITGA1 haplotype block 2 was a significant protective factor against gastric cancer in the both codominant model(OR=0.602,95%CI:0.212-0.709,P=0.021)and the dominant model(OR=0.653,95%CI:0.483-0.884).The ITGA1 gene showed a significant gene-based association with gastric cancer in the VEGAS test.In the dominant model,the A-T type of ITGA1 haplotype block 2 was a significant risk factor(OR=1.341,95%CI:1.034-1.741).SNP rs2447867 might be related to the severity of gastric epithelial injury due to inflammation and,thus,to the risk of developing gastric cancer.CONCLUSION:ITGA1 gene SNPs rs1862610,rs2432143,and rs2447867 and the ITGA1 haplotype block that includes SNPs rs1862610 and rs2432143 were significantly associated with gastric cancer.     

Bisphosphonate use and gastrointestinal tract cancer risk: Meta-analysis of observational studies

AIM: To perform a meta-analysis of observational studies to further elucidate the relationship between oral bisphosphonate use and gastrointestinal cancer risk.METHODS: Systematic literature search was conducted in MEDLINE, EMBASE, and the Cochrane Library to identify studies through January 2011. Search terms were “bisphosphonates” or trade names of the drugs, and “observational studies” or “cohort studies” or “case-control studies”. Two evaluators reviewed and selected articles on the basis of predetermined selection criteria as followed: (1) observational studies (case-control or cohort studies) on bisphosphonate use; (2) with at least 2 years of follow-up; and (3) reported data on the incidence of cancer diagnosis. The DerSimonian and Laird random effects model were used to calculate the pooled relative risk (RR) with 95% confidence interval (CI). Two-by-two contingency table was used to calculate the outcomes not suitable for meta-analysis. Subgroup meta-analyses were conducted for the type of cancer (esophageal, gastric and colorectal cancers). Sensitivity analyses were performed to examine the effect sizes when only studies with long-term follow-up (mean 5 years; subgroup 3 years) were included.RESULTS: Of 740 screened articles, 3 cohort studies and 3 case-control studies were included in the analyses. At first, 4 cohort studies and 3 case-control studies were selected for the analyses but one cohort study was excluded because the cancer outcomes were not categorized by type of gastrointestinal cancer. More than 124 686 subjects participated in the 3 cohort studies. The mean follow-up time in all of the cohort studies combined was approximately 3.88 years. The 3 case-control studies reported 3070 esophageal cancer cases and 15 417 controls, 2018 gastric cancer cases and 10 007 controls, and 11 574 colorectal cancer cases and 53 955 controls. The percentage of study participants who used bisphosphonate was 2.8% among the cases and 2.9% among the controls. The meta-analysis of all the studies found no significant association between bisphosphonate use and gastrointestinal cancer. Also no statistically significant association was found in a meta-analysis of long-term follow-up studies. There was no negative association between bisphosphonate use and the incidence of esophageal cancer in the overall analysis (RR 0.96, 95% CI: 0.65-1.42, I² = 52.8%, P = 0.076) and no statistically significant association with long-term follow-up (RR 1.74, 95% CI: 0.97-3.10, I² = 58.8%, P = 0.119). No negative association was found in the studies reporting the risk of gastric cancer (RR 0.89, 95% CI: 0.71-1.13, I² = 0.0%, P = 0.472). In case of colorectal cancer, there was no association between colorectal cancer and bisphosphonate use (RR 0.62, 95% CI: 0.30-1.29, I² = 88.0%, P = 0.004) and also in the analysis with long-term follow-up (RR 0.61, 95% CI: 0.28-1.35, I² = 84.6%, P = 0.011).CONCLUSION: Oral bisphosphonate use had no significant effect on gastrointestinal cancer risk. However, this finding should be validated in randomized controlled trials with long-term follow-up.     

GSTT1及GSTM1与急性髓系白血病疗效及预后的研究

目的探讨谷胱甘肽硫转移酶(GSTs)家族中GSTT1和GSTM1基因多态性与急性髓系白血病(AML)疗效,药物不良反应与预后的关系。方法AML患者180例,用多重PCR方法检测GSTT1和GSTM1基因型,比较不同基因型患者的诱导治疗完全缓解(CR)率,药物不良反应发生率,总体生存期,无复发生存期和复发率。结果(1)GSTT1和GSTM1基因双非缺失型(double-present型)患者一疗程CR率高于GSTT1,GSTM1任一基因缺失型(null型),二者差异有统计学意义(P=0.013),GSTT1/GSTM1的null基因型患者发生不CR的危险度是double-present型患者的8.736倍(95%CI1.146~66.574)。GSTT1present型一疗程CR率高于GSTT1null型,二者比较亦有统计学意义(P=0.021,OR=2.572,95%CI1.136~5.826);(2)GSTT1和GSTM1基因型分布与诱导治疗后中性粒细胞<0.5×109/L及PLT<20×109/L持续时间差异无统计学意义,GSTM1null型患者发生AST异常的危险度是GSTM1present型的2.593倍(P=0.016,95%CI1.176~5.717);(3)double-present型总体和无复发生存期较GSTT1/GSTM1的null型患者长(平均总体生存期为68.4、38.5个月,P=0.028;平均无复发生存期为73.5、34.9个月,P=0.014),GSTT1null型患者无复发生存期短于GSTT1present型患者(平均无复发生存期为26.7、64.3个月,P=0.038),但二者总体生存期无统计学意义(P=0.653)。double-present型患者复发率显著低于GSTT1/GSTM1的null型患者(13.3%、35.6%,P=0.019)。结论GSTT1,GSTM1基因型与AML患者治疗CR率、复发率、化疗的不良反应及预后均有显著相关性,GSTT1和GSTM1基因型有助于指导AML患者个体化治疗方案的制定。     

Association of genetic polymorphism of GSTT1, GSTM1 and GSTM3 in COPD patients in a north Indian population

Environmental exposures and genetic susceptibility can contribute to lung function decline in chronic obstructive pulmonary disease (COPD). Cigarette smoking is the main etiological factor for decline in lung function in COPD. However, only 10-20% chronic smokers develop symptomatic COPD. Genetic susceptibility to COPD might depend upon the variation of enzyme activities that detoxify cigarette smoke components. We performed a case control study to assess the association of Glutathione- S-transferase T1(GSTT1),Glutathione- S-transferase M1 (GSTM1), and Glutathione-S-transferase M3(GSTM3) common polymorphisms with the susceptibility to COPD patient in a north India population. In the present study, the genotypes of 412 subjects, (204 COPD patients and 208 healthy controls) were analyzed. Statistical analysis revealed that the frequency of homozygous GSTM1 null genotype was found to be significant higher in COPD patients as compared with healthy controls (OR, 2.58; 95% CI, 1.73-3.84; P = 0.001), but there were no significant differences in the distribution of homozygous null GSTT1 and 3-bp deletion polymorphism (rs1799735) in intron 6 variant allele in GSTM3 between COPD patients and healthy controls. Our study results suggest that GSTM1 null polymorphism is associated with genetic susceptibility to COPD. Moreover, we also found association between this polymorphism with pulmonary function test in smokers as well as nonsmokers.     

GSTT1, GSTM1 and CYP2E1 genetic polymorphisms in gastric cancer and chronic gastritis in a Brazilian population

MIM:To test the hypothesis that,in the Southeastern Brazilian population,the GSTT1,GSTM1 and CYP2E1 polymorphisms and putative risk factors are associated with an increased risk for gastric cancer.METHODS:We conducted a study on 100 cases of gastric cancer(GC),100 cases of chronic gastritis(CG),and 150 controls(C).Deletion of the GSTT1 and GSTM1 genes was assessed by multiplex PCR.CYP2E1/PsА genotyping was performed using a PCR-RFLP assay.RESULTS:No relationship between GSTT1/GSTM1 deletion and the c1/c2 genotype of CYP2E1 was observed among the three groups.However,a significant difference between CG and C was observde,due to a greater number of GSTT1/GSTM1 positive genotypes in the CG group.The GSTT1 null genotype occurred more frequently in Negroid subjicts,and the GSTM1 null genotype was observed mainly in individuals with chronic gastritis infected with H pylori.CONCLUSION:Our findings indecate that there is no obvious relationship between the GSTT1,GSTM1 and CYP2E1 polymorphisms and gastric cancer.     

Glutathione S-transferase M1 polymorphism and esophageal cancer risk: An updated meta-analysis based on 37 studies

AIM: To evaluate the relationship between glutathione S-transferase M1（GSTM1） polymorphism and susceptibility to esophageal cancer（EC）.METHODS: A comprehensive search of the United States National Library of Medicine Pub Med database and the Elsevier, Springer, and China National Knowledge Infrastructure databases for all relevant studies was conducted using combinations of the following terms: "glutathione S-transferase M1", "GSTM1", "polymorphism", and "EC"（until November 1, 2014）. The statistical analysis was performed using the SAS software（v.9.1.3; SAS Institute, Cary, NC, United States） and the Review Manager software（v.5.0; Oxford, England）; crude odds ratios（ORs） with 95% confidence intervals（CIs） were used to assess the association between the GSTM1 null genotype and the risk of EC.RESULTS: A total of 37 studies involving 2236 EC cases and 3243 controls were included in this metaanalysis. We observed that the GSTM1 null genotype was a significant risk factor for EC in most populations(OR = 1.33, 95%CI: 1.12-1.57, P_{heterogeneity} < 0.000001, and I2 = 77.0%), particularly in the Asian population(OR = 1.53, 95%CI: 1.26-1.86, P_{heterogeneity}< 0.000001, and I2 = 77.0%), but not in the Caucasian population(OR = 1.02, 95%CI: 0.87-1.19, P_{heterogeneity} = 0.97, and I2 = 0%).CONCLUSION: The GSTM1 null polymorphism may be associated with an increased risk for EC in Asian but not Caucasian populations.     

Polymorphic variants of GSTM1, GSTT1, and GSTP1 genes in childhood acute leukemias: A preliminary study in Argentina

Abstract

Background and Aim

Despite recent major advances in leukemia research, the etiopathogenesis of childhood leukemias remains far elusive. Individual predisposing factors, including polymorphisms in detoxification enzymes, have been implicated in the molecular pathogenesis and heterogeneity of the disease. Genetic polymorphisms of glutathione S-transferases (GSTs) that alter enzyme activity could be an additional factor that increases the risk of acute leukemia, but data are lacking in Argentina. We assessed the association of GST polymorphisms and the susceptibility to childhood leukemia in Argentina by conducting an exploratory case-control study and correlated patients’ genotype to clinical and biological features.

Methods

Deletion polymorphisms in GSTM1 and GSTT1 genes and the single nucleotide polymorphism in GSTP1 c.313A>G (rs1695; p.105Ile>Val) were genotyped by PCR-RFLP in 36 patients and 133 healthy individuals.

Results

GSTM1-null genotype was associated with a lower risk of developing acute leukemia (P = 0.013; OR: 0.31; CI: 0.12–0.80), while GSTP1-GG variants displayed an increased risk (P = 0.01; OR: 3.9; CI: 1.85–8.2). However, no differences were found for GSTT1 gene.

Conclusion

These preliminary results, to be validated in a larger population from Argentina, suggest that the development of pediatric leukemia may be differentially influenced by polymorphic variants in GST genes.