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Glutathione S-Transferase Polymorphisms (GSTM1, GSTT1 and GSTP1) and Their Susceptibility to Renal Cell Carcinoma: An Evidence-Based Meta-Analysis  [PDF]
Xingliang Yang, Shuyu Long, Jianping Deng, Tianxing Deng, Zhihua Gong, Ping Hao
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0063827
Abstract: Background The association of the three Glutathione S-transferases (GSTs) polymorphisms (GSTM1, GSTT1 and GSTP1) genotypes with their individual susceptibilities to renal cell carcinoma (RCC) has not been well established. We performed a quantitative meta-analysis to assess the possible associations between the GSTM1, GSTT1 and GSTP1 genotypes and their individual susceptibilities to renal cell carcinoma. Methods We systematically searched the PubMed, CNKI and Embase databases to identify the relevant studies. Finally, 11 eligible studies were selected. The pooled odds ratios (ORs) with their 95% confidence intervals (CIs) were used to assess the association between the GSTs polymorphisms and the risk of RCC. Multiple subgroup analyses and quality assessment of the included studies were performed based on the available information. Results None of the GSTs polymorphisms had a significant association with the RCC risk. Similar results were found in the subgroup analyses, except for the GSTs polymorphisms in the situations described below. The GSTM1 and GSTT1 active genotypes in subjects exposed to pesticides (GSTM1: OR = 3.44; 95% CI, 2.04–5.80; GSTT1: OR = 2.84; 95% CI, 1.75–4.60), most of the GSTs genotypes in Asian populations (GSTT1: OR = 2.39, 95% CI = 1.63–3.51; GSTP1: Dominant model: OR = 1.50, 95% CI = 1.14–1.99; Additive model: OR = 1.39, 95% CI = 1.12–1.73; AG vs. AA: OR = 1.47, 95% CI = 1.10–1.97; GG vs. AA: OR = 1.82, 95% CI = 1.07–3.09) and the dual null genotype of GSTT1-GSTP1 (OR = 2.84, 95% CI = 1.75–4.60) showed positive associations with the RCC risk. Conclusion Our present study provides evidence that the GSTM1, GSTT1 and GSTP1 polymorphisms are not associated with the development of RCC. However, more case-control studies are needed for further confirmation.
No association between the GSTM1 and GSTT1 polymorphism and endometrial cancer risk: A meta-analysi  [PDF]
Marce-Amara Kpoghomou, Fatch W. Kalembo, Joella Eldie Soatiana
Open Journal of Obstetrics and Gynecology (OJOG) , 2013, DOI: 10.4236/ojog.2013.34072
Abstract:

Purpose: A number of case-control studies have been conducted to investigate the association of glutathione S-transferase (GST) genetic polymorphisms and endometrial carcinoma risk. However, these studies have yielded contradictory results. We therefore performed a meta-analysis to derive a more precise estimation of the association between polymorphisms on GSTM1, GSTT1 and endometrial carcinoma. Methods: Identification of relevant studies was carried out through a search in the following databases Medline, EMbase andChinaNational Knowledge International (CNKI) up to March. 2013. All case-control studies that investigated the association between GS-TM1 and GSTT1 gene polymorphisms and risk of endometrial cancer were included in the study. The pooled odds ratio (OR) was used for analyses of results and the corresponding 95% confidence intervals (CI) were estimated. Result: Six published case-control studies of association between the GSTM1 and GSTT1 polymorphism and endometrial cancer risk covering 3558 subjects were included in the metaanalysis, but the results indicated that the null genotypes of GSTM1 and GSTT1 polymorphisms were not associated with a significantly increased risk of endometrial cancer (for GSTM1: OR = 0.99; 95% CI, 0.86 - 1.4; for GSTT1: OR = 0.96; 95% CI, 0.80 - 1.14, respectively). Conclusion: This meta-analysis suggests that GSTM1 and GSTT1 polymorphism may not be associated with increased risk of endometrial cancer. To validate the association between polymorphism and endometrial cancer, further studies with larger numbers of participants worldwide are needed.

Polymorphism of GSTM1 and GSTT1 genes in prostate cancer: A study from North India  [cached]
Mittal Rama Devi,Srivastava D,Mandhani A,Kumar A
Indian Journal of Cancer , 2004,
Abstract: BACKGROUND : Glutathione-S-transferases (GSTs) are active in the detoxification of wide variety of endogenous or exogenous carcinogens. The genetic polymorphisms of GSTM1 and GSTT1 genes have been studied earlier to evaluate the relative risk of various cancers. AIM, SETTING AND DESIGN : In the present study, we examined the association of the GSTM1 and GSTT1 gene polymorphisms with sporadic prostate cancer patients in north Indian population. MATERIAL AND METHODS : This case control study was undertaken over a period of 24 months and included 103 prostate cancer patients and 117 controls; both patients and controls originated from northern part of India. The GSTT1 and GSTM1 genotypes were identified by multiplex PCR in peripheral blood DNA samples. STATISTICAL ANALYSIS : Difference in genotype prevalence and association between case and control group were assessed by the Chi square and Fisher Exact tests. RESULTS : Frequencies of null genotypes in GSTT1 and GSTM1, was 11% (13/117) and 30% (35/117) respectively in control individuals. The frequencies of GSTT1 and GSTM1 null genotypes in prostate cancer patients were 34% (35/103) and 53% (55/103) respectively. CONCLUSION : Our study demonstrates that the null genotypes of GSTT1 and GSTM1 are substantially at higher risk for prostate carcinoma as compared to the normal healthy controls. The GSTT1 and GSTM1 null genotypes did not show significant association with tobacco usage in prostate cancer patients. However, the null genotypes were significantly stratified in 50-60 year-old patients when incidence of prostate cancer is high.
Maternal Smoking,GSTM1 and GSTT1 Polymorphism and Susceptibility to Adverse Pregnancy Outcomes  [PDF]
Regina Grazuleviciene,Asta Danileviciute,Ruta Nadisauskiene,Jone Vencloviene
International Journal of Environmental Research and Public Health , 2009, DOI: 10.3390/ijerph6031282
Abstract: The objective of the study was to investigate the association between maternal smoking, GSTM1, GSTT1 polymorphism, low birth weight (LBW, < 2,500 g) and intra-uterine growth restriction (IUGR, < 2,500 g and gestation ≥ 37 weeks) risk. Within a prospective cohort study in Kaunas (Lithuania), a nested case-control study on LBW and IUGR occurrence among 646women with genotyping of GSTT1 and GSTM1 polymorphisms who delivered live singletons was conducted. Multivariate logistic regression analysis was used to study the association of maternal smoking and polymorphism in two genes metabolizing xenobiotics. Without consideration of genotype, light-smoking (mean 4.8 cigarettes/day) during pregnancy was associated with a small increase in LBW risk, adjusted OR 1.21; 95% CI 0.44 – 3.31. The corresponding odds for IUGR risk was 1.57; 95% CI 0.45 – 5.55. The findings suggested the greater LBW risk among light-smoking mothers with the GSTM1-null genotype (OR 1.91; 95% CI 0.43 – 8.47) compared to those with GSTM1-present genotype (OR 1.11; 95% CI 0.26 – 4.47). When both GSTM1 and GSTT1 genotypes were considered, the synergistic effect was found among smoking mothers: GSTT1-present and GSTM1-null genotype OR for LBW was 3.31; 95% CI 0.60-18.4 and that for IUGR was 2.47; 95% CI 0.31 – 13.1. However there was no statistically significant interaction between maternal smoking, GSTT1- present and GSTM1-null genotypes for LBW (OR 1.45; 95% CI 0.22 – 10.1, p = 0.66) and for IUGR (OR 1.10; 95% CI 0.10 – 12.6, p = 0.93).The results of this study suggested that smoking, even at a low-level, ought to be considered a potential risk factor for adverse birth outcomes and that genetic polymorphism may contribute to individual variation in tobacco smoke response.
Genetic Polymorphisms of Glutathione S-Transferase Genes GSTM1, GSTT1 and Risk of Hepatocellular Carcinoma  [PDF]
Kang Song, Jiayong Yi, Xizhong Shen, Yu Cai
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0048924
Abstract: Background A number of case-control studies were conducted to investigate the association of glutathione S-transferase (GST) genetic polymorphisms and hepatocellular carcinoma (HCC) risk. However, these studies have yielded contradictory results. We therefore performed a meta-analysis to derive a more precise estimation of the association between polymorphisms on GSTM1, GSTT1 and HCC. Methodology/Prinicpal Findings PubMed, EMBASE, ISI web of science and the CNKI databases were systematically searched to identify relevant studies. Data were abstracted independently by two reviewers. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were used to assess the strength of association. Potential sources of heterogeneity were also assessed by subgroup analysis and meta-regression. Funnel plots and Egger’s linear regression were used to test publication bias among the articles. A total of 34 studies including 4,463 cases and 6,857 controls were included in this meta-analysis. In a combined analysis, significantly increased HCC risks were found for null genotype of GSTM1 (OR = 1.29, 95% CI: 1.06–1.58; P = 0.01) and GSTT1 (OR = 1.43, 95% CI: 1.22–1.68; P<10?5). Potential sources of heterogeneity were explored by subgroup analysis and meta-regression. Significant results were found in East Asians and Indians when stratified by ethnicity; whereas no significant associations were found among Caucasians and African populations. By pooling data from 12 studies that considered combinations of GSTT1 and GSTM1 null genotypes, a statistically significant increased risk for HCC (OR = 1.88, 95% CI: 1.41–2.50; P<10?4) was detected for individuals with combined deletion mutations in both genes compared with positive genotypes. Conclusions/Significance This meta-analysis suggests that the GSTM1 and GSTT1 null genotype may slightly increase the risk of HCC and that interaction between unfavourable GSTs genotypes may exist.
Análise dos genes GSTM1 e GSTT1 em pacientes com cancer de cabe?a e pesco?o
Leme, Cássia Veridiana Dourado;Raposo, Luis Sérgio;Ruiz, Mariangela Torreglosa;Biselli, Joice Matos;Galbiatti, Ana Lívia Silva;Maniglia, José Victor;Pavarino-Bertelli, érika Cristina;Goloni-Bertollo, Eny Maria;
Revista da Associa??o Médica Brasileira , 2010, DOI: 10.1590/S0104-42302010000300013
Abstract: objective: to establish the clinical and demographic profile and identify risk factors among patients with head and neck cancer and relate them to the polymorphism of gstt1 and gstm1. methods: one hundred patients with head and neck cancer and 100 control group individuals without history of neoplasm were analyzed. . the molecular analysis were made by multiplex polymerase chain reaction. for statistical analysis, data were tabulated and compared by the fishera€?s exact test, the chi-square test and multiple logistic regression were also used. results: there was prevalence of smokers (or = 5.32, ci 95% ci = 2.04-13.86 p = 0.0006), alcohol drinkers (or = 5.04, ci 95% = 2.19-11.59 p = 0.0001) in head and neck cancer patients . the gstt1 null genotype was found in 47% of the patient and 41% of the control group (or = 0.67; ci 95%= 0.34-1.35; p = 0.2648). likewise , the gstm1 null genotype was found in 66% of the patient and 75% of the control group (or = 2.25; ci 95%= 1.05 - 4.84; p = 0.0368). the combined gstt1 and gstm1 gene null genotype shown association between gstm1*0/gstt1 and occurrence of head and neck carcinoma (or = 7.64; ci 95%= 1.72-34.04; p = 0.0076). analysis of clinical-pathological features showed association between gstt1 null genotype and larynx, the inverse relation between this genotype and pharynx. conclusion: in our study it was possible to establish association between gstm1 null genotypes and head and neck cancer.
CYP1A1, GSTM1 and GSTT1 Genetic Polymorphism in Egyptian Chronic Myeloid Leukemia Patients
Shereen Mahmoud,Dalia A. Labib,Rania H. Khalifa,Reham E. Abu Khalil
Research Journal of Immunology , 2010,
Abstract: The genetic polymorphism of xenobiotic metabolizing enzymes: phase I enzymes; cytochrome P450 (CYP1A1) and phase II enzymes; glutathione S-transferase (GSTM1 and GSTT1), were analyzed in 30 chronic myeloid leukemia patients (CML) (19 females, 11 males; age (Mean±SD) 41.7±9.5 years) and 20 age and sex matched healthy controls. The frequency of CYP1A1 alleles and of GSTT1 and GSTM1 homozygous deletions was examined by PCR- RFLP and PCR methods, respectively, using blood samples. The relationship between these genotypes and risk of CML was assessed by means of Odds Ratio (OR) with 95% confidence limits. Present results showed that the frequency of the mutant allele CYP1A1*2A was found to be 3.3% in CML patients and 45% in controls (OR = 0.042, 95% CI: 0.005-0.373; p<0.001), suggesting that this polymorphic variant may be a protective factor against CML. The frequency of individuals carrying the GSTT1 null genotype was higher among CML patients (60%) compared to controls (15%) (OR = 8.5, 95% CI: 2.038-35.458; p = 0.002). Therefore, GSTT1 null genotype may be a risk factor for CML. Although, GSTM1 null genotype frequency was slightly higher in the patient group (46.7%) than in the controls (40%), this difference was not statistically significant (OR = 1.313, 95% CI: 0.417-4.131; p = 0.642). In conclusion this data suggests that polymorphic CYP1A1 and GSTT1 genes appear to affect susceptibility to CML.
Polimorfismos GSTT1 e GSTM1 em indivíduos tabagistas com carcinoma espinocelular de cabe?a e pesco?o
Biselli, Joice Matos;Leal, Renata Cristina de Angelo Calsaverini;Ruiz, Mariangela Torreglosa;Goloni-Bertollo, Eny Maria;Maníglia, José Victor;Rossit, Andréa Regina Baptista;Pavarino-Bertelli, érika Cristina;
Revista Brasileira de Otorrinolaringologia , 2006, DOI: 10.1590/S0034-72992006000500012
Abstract: gene variability related to carcinogen activation and detoxification may interfere with susceptibility to head and neck cancer. aim: to investigate the relation between gstt1 and gstm1 null polymorphisms and the risk of head and neck squamous cell carcinoma in cigarette smokers. material and method: a case-control study conducted at the sao jose do rio preto medical school, brazil. gstm1 and gstt1 null genotype frequencies were evaluated by multiplex pcr in 45 cigarette smokers with head and neck squamous cell carcinomas and 45 cigarette smokers without this disease. results: the oral cavity was the most prevalent tumor site for squamous cell carcinoma. the gstt1 null genotype was found in 33.3% of the experimental group and 23.3% of the control group (p= 0.311). experimental and control groups had gstm1 null genotype frequencies of 35% and 48.3% (p=0.582). no association between alcohol consumption and gstt1 and gstmi null genotypes was found in these groups (p-values>0.05). there were more men, and alcohol consumption was prevalent in both groups. conclusion: in this study we were unable to show a correlation between gstm1 and gstt1 genotypes and the development of head and neck squamous cell carcinomas in cigarette smokers.
Protection against laryngeal and pharyngeal carcinoma: Heterozygous vs. homozygous deletions of GSTM1 and GSTT1
Masood, Nosheen;Kayani, Mahmood Akhtar;
Genetics and Molecular Biology , 2013, DOI: 10.1590/S1415-47572013005000006
Abstract: deletions in gstm1 and gstt1 genes are considered to be a risk factor for cancer development but the exact location of these deletions in the genome was unknown. three main objectives of the current study were to: (a) identify the boundaries of these deletions in the human genome, (b) screen homozygous (-/-) and heterozygous (+/-) deleted, as well as homozygous present (+/+) individuals using pcr assays, (c) detect associations of pharyngeal (pc) and laryngeal cancer (lc) with the respective genotypes. in total, 102 pc and 92 lc patients were screened and compared with 150 controls. pcr mapping and sequencing revealed a 6 kbp deletion for gstm1 and a 9 kbp deletion for the gstt1 gene. the mean age of pc cases was 48.1 (±16.7) years; for lc cases it was 48.5 (±17.4) years and for controls 46 (±17.7) years. the or (odds ratio) for the gstm1 null genotype in pc and lc cases was 10.2 and 1.0 (95% ci 5.04-20.7 and 1.1-1.7) respectively. similarly, for gstt1 the or was 4.02 with a 95% ci of 2.3-7.1 in pc cases. for lc cases the or was 0.8 with 95% ci of 0.4-1.7. a non-significant number of lc and pc patients had heterozygous deletions of gstm1 compared to controls (od 0.5, 95% ci 0.2- 1.6 and or 0.5, 95% ci 0.2- 1.5 respectively). the gstt1 gene also showed a non-significant association in pc (od 0.9, 95% ci 0.4-1.9), as well as in lc patients (od 0.7, 95% ci 0.3-1.7). the homozygous genotype was significantly associated with pc and lc, whereas the heterozygous was not so. the gstm1 (-/-) and gstt1 (-/-) genotypes are a risk factor for lc and pc, whereas the (+/-) genotypes are not.
Association between GSTM1 and GSTT1 Allelic Variants and Head and Neck Squamous Cell Cancinoma  [PDF]
Yang Zhang, Yuanyuan Ni, Hao Zhang, Yongchu Pan, Junqing Ma, Lin Wang
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0047579
Abstract: Backgrounds GSTM1 and GSTT1 are involved in the detoxification of carcinogens such as smoking by-products, and polymorphisms in these two genes with a result of loss of enzyme activity may increase risk of carcinogenesis. Although many epidemiological studies have investigated the association between GSTM1 or GSTT1 null genotype and head and neck squamous cell carcinoma (HNSCC), the results remain conflicting. To elucidate the overall association of GSTM1, GSTT1 and HNSCC, we included all available studies and performed this meta-analysis. Methodology/Principal Findings A dataset including 42 articles for GSTM1, 32 articles for GSTT1, and 15 articles for GSTM1 and GSTT1 in combination were identified by a search in PubMed. Associations beween HNSCC and polymorphisms of GSTM1 and GSTT1 alone and in combination were analysed by software RevMan 5.1. Stratification analysis on ethnicity and smoking status, sensitivity analysis, heterogeneity among studies and their publication bias were also tested. Association was found in overall analysis between HNSCC and GSTM1 and GSTT1 null genotype. Stratified by ethnicity, we found increased risks of HNSCC in carriers with GSTM1 null genotype in Asian, GSTT1 null genotype in South American, and dual null genotype in European and Asian. When stratified by smoking, a more significant association of GSTM1 null genotype with HNSCC risk was observed in smokers. Conclusions/Significance This meta-analysis presented additional evidence of the association between GSTM1 and GSTT1 polymorphisms and HNSCC risk.
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