• Title/Summary/Keyword: Glutathione S-transferase M1 gene (GSTM1)

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Association between the Polymorphism of Glutathione S-transferase Genes and Chronic Myeloid Leukemia in Asian Population: a Meta-analysis (아시아인종에서 만성골수성백혈병과 Glutathione S-transferase 유전자 다형성의 메타분석)

  • Kim, Hee Sung
    • The Journal of the Korea Contents Association
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    • v.17 no.10
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    • pp.289-299
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    • 2017
  • To verify the association between susceptibility to chronic myeloid leukemia (CML) and GSTM1, GSTT1 gene polymorphisms in Asian populations, 9 papers published until July 2017 were cited in a meta-analysis. The null present types of the GSTM1, GSTT1 gene were analyzed individually. The significant association was found between CML and GST polymorphism (GSTM1; OR=1.306, 95% CI=1.091-1.563, p=0.004, GSTT1; OR=1.987, 95% CI=1.438-2.746, p=0.000). In addition, there was association between CML and the null type of the combination GSTM1-GSTT1 polymorphisms (OR=4.191, 95% CI=2.833-6.201, p=0.000). Thus, genetic polymorphisms of the GSTM1, GSTT1 and combination GSTM1-GSTT1 polymorphism in Asian populations may be risk factors for CML.

Lack of Association of Glutathione S-transferase M3 Gene Polymorphism with the Susceptibility of Lung Cancer

  • Feng, Xu;Dong, Chun-Qiang;Shi, Jun-Jie;Zhou, Hua-Fu;He, Wei;Zheng, Bao-Shi
    • Asian Pacific Journal of Cancer Prevention
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    • v.13 no.9
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    • pp.4465-4468
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    • 2012
  • Objective: The conclusions of published reports on the relationship between the glutathione S-transferase M3 (GSTM3) A/B gene polymorphism and the risk of lung cancer are still debated. This meta-analysis was performed to evaluate the association between GSTM3 and the risk of lung cancer. Methods: Association investigations were identified from PubMed, Embase, and Cochrane Library, and eligible studies were included and synthesized using a meta-analysis method. Results: Eight reports were included into this meta-analysis for the association of GSTM3 A/B gene polymorphism and lung cancer susceptibility, covering 1,854 patients with lung cancer and 1,926 controls. No association between the GSTM3 A/B gene polymorphism and lung cancer was found in this meta-analysis (B allele: OR = 1.25, 95% CI: 0.89-1.76, P = 0.20; BB genotype: OR = 1.53, 95% CI: 0.71-3.32, P = 0.28; AA genotype: OR = 0.85, 95% CI: 0.59-1.23, P = 0.39). Conclusions: The GSTM3 A/B gene polymorphism is not associated with lung cancer susceptibility. However, more studies on the relationship between GSTM3 A/B gene polymorphism and the risk of lung cancer should be performed in the future.

Glutathione S-transferase M1 Null Genotype and Hepatocellular Carcinoma Susceptibility in China and India: Evidence from an Updated Meta-analysis

  • Liu, Hong-Zhou;Peng, Jie;Peng, Chun-Yan;Yan, Ming;Zheng, Fang
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.12
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    • pp.4851-4856
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    • 2014
  • Background: Glutathione S-transferase M1 (GSTM1) have been reported to be associated with hepatocellular carcinoma. However, the effect of the GSTMl null genotype was divergent in the literature and we therefore performed the present meta-analysis to explore the relationship in detail. Materials and Metbods: Reported studies were searched from 1990 to March 1, 2014 in PubMed and Wanfang Med Online. The total odds oatio (OR) and 95% CI were calculated and analyzed by Review Manager 5.1 and STATE 12. Results: Total OR was calculated from 26 articles with 3,769 cases and 5,517 controls and the association proved significant (OR [95%CI]=1.50 [1.25, 1.80], P<0.05) in the Chinese population. However, there was no significant association between hepatocellular carcinoma risk among subjects carrying the GSTM1 null genotype (OR [95%CI]=1.20 [0.88-1.64], P=0.24) in subgroups of publication in English and in Indian populations (OR [95%CI]=1.80 [0.80-4.20], P=0.15). Conclusions: The GSTM1 deletion polymorphism might not have a significant effect on the susceptibility of hepatocellular carcinoma overall.

Role of GSTM1 Copy Number Variant in the Prognosis of Thai Colorectal Cancer Patients Treated with 5-FU-based Chemotherapy

  • Pongtheerat, Tanett;Saelee, Pensri
    • Asian Pacific Journal of Cancer Prevention
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    • v.17 no.10
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    • pp.4719-4722
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    • 2016
  • Background: Glutathione S-transferase M1 (GSTM1) is involved in the detoxification of carcinogenic agents. DNA copy number variants of GSTM1 may be associated with cancer progression and may result in reduced survival time of various cancers. Determination of DNA copy number variants was here used to assess the association between GSTM1 copy number variant and pathological status and survival time of colorectal-cancer patients treated with 5-fluorouracil-based chemotherapy. Methods: One hundred thirteen Thai colorectal-cancer patients were investigated for GSTM1 copy number variant by real-time PCR. Relationships between gene copy number variants and clinico-pathological parameters were determined. Result: Associations were evident between GSTM1 copy number and stage of tumor (P = 0.026) and metastasis at diagnosis (P = 0.049), with odds ratio values of 0.2 and 0.3 respectively. Conclusions: GSTM1 copy number variant was here not related with reduced overall survival for the colorectal-cancer patients receiving 5-FU-based chemotherapy.

Genetic Polymorphisms of Glutathione S-transferase M1 and Prostate Cancer Risk in Asians: A Meta-analysis of 18 Studies

  • Hu, Zheng-Hui;Lin, Yi-Wei;Xu, Xin;Chen, Hong;Mao, Ye-Qing;Wu, Jian;Zhu, Yi;Xu, Xiang-Lai;Xie, Li-Ping
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.1
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    • pp.393-398
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    • 2013
  • Background: Many studies have investigated associations between the glutathione S-transferase M1 (GSTM1) null polymorphism and risk of prostate cancer, but the impact of GSTM1 in people who live in Asian countries is still unclear owing to inconsistencies across results. Methods: We searched the PubMed, Web of Science, Scopus, Ovid and CNKI databases for studies of associations between the GSTM1 null genotype and risk of prostate cancer in people who live in Asian countries, and estimated summary odds ratios (ORs) with 95% confidence intervals (95% CIs). Results: A total of 18 case-control studies with 2,172 cases and 3,258 controls were included in this meta-analysis, which showed the GSTM1 null genotype to be significantly associated with increased risk of prostate cancer in people who live in Asian countries (random-effects OR=1.74, 95% CI1.44-2.09, P<0.001). Similar results were found in East Asians (OR=1.41; 95% CI: 1.12-1.78; P=0.004) and Caucasians in Asia (OR=2.19; 95% CI: 1.85-2.60; P<0.001). No evidence of publication bias was observed. Conclusions: This meta-analysis of available data suggested that the GSTM1 null genotype does contribute to increased risk of prostate cancer in people who live in Asian countries.

Null Glutathione S-transferase T1 and M1 Genotypes and Oral Cancer Susceptibility in China and India - a Meta-analysis

  • Peng, Jie;Liu, Hong-Zhou;Zhu, You-Jia
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.1
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    • pp.287-290
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    • 2014
  • Objective: Genetic variation is considered to strongly impact on detoxification of carcinogens and therefore is related to cancer risk. However, findings for the null genotypes of GSTT1 and GSTM1 have not always been consistent. Therefore the present meta-analysis was conducted. Methods: We accessed the reported study at different research areas and used various databases, including PubMed and Wanfang Med Onlion from 1990 to May 1st 2013. We calculated the odds ratio (OR), 95% confidence interval (CI) and P value for oral cancer by using Review Manager 5.1 and STATE 12. Results: We found that there was no increased oral cancer risk among subjects carrying GSTM1 and GSTT1 null genotype (OR=1.35, 95%CI=0.68-2.68, P=0.39) and (OR=1.41, 95%CI=0.72-2.77, P=0.31) in the Chinese population. In contrast, in studies in India a significant correlation between GSTM1 null genotype and oral cancer was observed (OR=1.59, 95%CI=1.20-2.11, P=0.001), but not in GSTT1 (OR=1.21, 95% CI=0.84-1.74, P=0.31). Conclusion: We discovered that GSTM1 deletion polymorphism had a significant effect on the susceptibility of oral cancer in the Indian population.

Association Study of Glutathione-S-Transferase M1/T1 Gene Polymorphism with Deficiency-Excess Differentiation-syndrome in Korean Bronchial Asthmatics (한국인 기관지 천식 환자에서 허설변증과 Glutathione-S-Transferase 유전자의 다형성 연구)

  • Yu, Seung-Ryeol;Jeong, Seung-Yeon;Jung, Ju-Ho;Kim, Jin-Ju;Jung, Sung-Ki
    • The Journal of Internal Korean Medicine
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    • v.28 no.3
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    • pp.453-463
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    • 2007
  • Backgrounds : Glutathione-s-transferase (GST) is a kind of phase II metabolism enzyme and plays an important role in the detoxification of various toxic chemicals. It was reported that the genetic polymorphism of GSTM1 and GSTT1 genes may be responsible for asthma development and susceptibility to allergy. Traditional oriental medicine uses a unique diagnostic technique. differentiation-syndrome. to analyze signs and symptoms of patients synthetically. Through differentiation-syndrome. asthma patients can be divided into two groups: the deficiency syndrome group (DSG) and the excess syndrome group (ESG). Objectives : The purpose of this study was to investigate the possible association of GST gene polymorphism with clinical phenotype by differentiation-syndrome of bronchial asthma patients. Materials and Methods : One hundred and ten participants were evaluated by pulmonary function test. Patients with 53 DSG and 31 ESG by differentiation-syndrome were assessed for genetic analysis. GSTM1 and GSTT1 deletion polymorphism was performed by polymerase chain reaction (PCR). Results : GSTM1 gene deletion was detected in 43.4% of individuals in the DSG and in 38.71 % in the ESG. The distribution of GSTM1 polymorphism between DSG and ESG was not significantly different [$x^2$=0.1767, p=0.6742; OR(95% CI)=1.2139(0.4915-2.9979)]. The proportion of GSTT1 null genotypes was 41.51% in the DGS and 45.16% in the ESG. The distribution of GSTT1 polymorphism between DSG and ESG was also not significantly different [$x^2$=0.1065, p=0.7442; OR(95% CI)=0.8618(0.3525-2.1065)]. In the combined analysis of GSTM1 and GSTT1 genes, the frequency of both null type of GSTM1/GSTT1 genes was not significantly different from both positive type of GSTM1/GSTT1 genes[$x^2$=0.0768, p=0.7817; OR(95% CI)=1.2000(0.3303-4.3602)] Conclusions : These results indicate that polymorphism of the GST gene might not be associated with the symptomatic classification of DSG and ESG by differentiation-syndrome in Korean asthmatics.

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Association Between GSTM1 Polymorphism and Nasopharyngeal Cancer Susceptibility: a Meta-analysis

  • Sun, Zhen-Feng;Zhang, Jia;Xu, Hong-Ming;Wang, Guo-Liang;Dong, Pin
    • Asian Pacific Journal of Cancer Prevention
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    • v.13 no.11
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    • pp.5817-5821
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    • 2012
  • Background/Aims: Glutathione S-transferase M1 (GSTM1) is a multifunctional enzyme that plays a critical role in the detoxification of varieties of carcinogenic metabolites. Many studies have been conducted to investigate the association between GSTM1 polymorphism and nasopharyngeal cancer (NPC) risk, but the findings among those studies are inconsistent. To assess this relationship more precisely, we performed a meta-analysis of all available studies on the subject. Methods: Case-control studies were identified by searching Pubmed, Embase, ISI Web of Science, and Wanfang databases through September 6, 2012. We used the pooled odds ratio (OR) with its corresponding 95% confidence interval (95%CI) to evaluate the association of GSTM1 polymorphism with NPC susceptibility. Subgroup analyses by pathological types, sex and smoking status were performed to further identify the association. Results: Overall, 11 published studies with 1,513 cases and 2,802 controls were finally included into this meta-analysis according to the inclusion criteria. Meta-analysis of total studies showed that the null genotype of GSTM1 was significantly associated with increased risk of NPC, when comparing with the non-null genotype (OR=1.51, 95%CI=1.33-1.72, POR<0.001). The association was still statistically significant in subgroup analysis of patients with nasopharyngeal squamous cell carcinoma (OR=1.73, 95%CI=1.24-2.42, POR=0.001). Males with the null genotype of GSTM1 were more likely to subject to NPC than females. In addition, the association between the null genotype of GSTM1 and NPC risk was strongest in individuals with exposure to smoking. Sensitivity analysis by sequential omission of any individual studies one at a time further demonstrated the significant association. Conclusions: The findings suggest that the null genotype of GSTM1 is a risk factor for NPC, and there is a gene-smoking interaction in this association.

Effects of lymphocyte DNA damage levels in Korean plant food groups and Korean diet regarding to glutathione S-transferase M1 and T1 polymorphisms (건강한 성인의 glutathione S-transferase M1과 T1 유전자 다형성에 따른 한식에서의 식물성 식품군과 한식의 DNA 손상 감소 효과)

  • Kim, Hyun-A;Lee, Min-Young;Kang, Myung-Hee
    • Journal of Nutrition and Health
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    • v.50 no.1
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    • pp.10-24
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    • 2017
  • Purpose: GST (glutathione S-transferase) M1 and T1 gene polymorphisms are known to affect antioxidant levels. This study was carried out to evaluate genetic susceptibility by measuring the effect of DNA damage reduction in the Korean diet by vegetable food according to GST gene polymorphisms using the ex vivo method with human lymphocytes. Methods: Vegetable foods in the Korean diet based the results of the KNHANES V-2 (2011) were classified into 10 food groups. A total of 84 foods, which constituted more than 1% of the total intake in each food group, were finally designated as a vegetable food in the Korean diet. The Korean diet applied in this study is the standard one-week meals for Koreans (2,000 Kcal/day) suggested by the 2010 Dietary Reference Intakes for Koreans. Ex vivo DNA damage in human lymphocytes was assessed using comet assay. Results: In the Korean food group, the DNA damage protective effect of GSTM1 and GSTT1 was found to be greater in mutant type and wild-type, respectively. and the DNA damage protective effect according to the combined genotype of GSTM1 and GSTT1 was different depending on the food group. On the other hand, in Korean Diet, the DNA damage protective effect appeared to be larger in GSTM1 wild-type than in mutant type and was found to not be affected by GSTT1 genotype. Conclusion: These results can be used as basic data to demonstrate the superiority of the antioxidant function of Korean dietary patterns and food groups. Furthermore, it may be a starting point to begin research on customized antioxidant nutrition according to individual genes.

Lymphocyte DNA Damage and Anti-Oxidative Parameters are Affected by the Glutathione S-Transferase (GST) M1 and T1 Polymorphism and Smoking Status in Korean Young Adults (흡연 여부에 따른 Glutathione S-transferase (GST) M1 및 T1 유전자 다형성이 우리나라 젊은 성인의 임파구 DNA 손상과 항산화 영양상태 지표들 간의 관련성에 미치는 영향)

  • Han, Jeong-Hwa;Lee, Hye-Jin;Kang, Myung-Hee
    • Journal of Nutrition and Health
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    • v.44 no.5
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    • pp.366-377
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    • 2011
  • Glutathione S-transferase (GST) is a multigene family of phase II detoxifying enzymes that metabolize a wide range of exogenous and endogenous electrophilic compounds. GSTM1 and GSTT1 gene polymorphisms may account for inter-individual variability in coping with oxidative stress. We investigated the relationships between the level of lymphocyte DNA and antioxidative parameters and the effect on GST genotypes. GSTM1 and GSTT1 were characterized in 301 young healthy Korean adults and compared with oxidative stress parameters such as the level of lymphocyte DNA, plasma antioxidant vitamins, and erythrocyte antioxidant enzymes in smokers and non smokers. GST genotype, degree of DNA damage in lymphocytes, erythrocyte activities of superoxide dismutase, catalase, and glutathione peroxidase (GSH-Px), and plasma concentrations of total radical-trapping antioxidant potential (TRAP), vitamin C, ${\alpha}$- and ${\gamma}$-tocopherol, ${\alpha}$- and ${\beta}$-carotene, and cryptoxanthin were analyzed. Lymphocyte DNA damage assessed by the comet assay was higher in smokers than that in non-smokers, but the levels of plasma vitamin C, ${\beta}$-carotene, TRAP, erythrocyte catalase, and GSH-Px were lower than those of non-smokers (p < 0.05). Lymphocyte DNA damage was higher in subjects with the GSTM1- or GSTT1-present genotype than those with the GSTM1-present or GSTT1- genotype. No difference in erythrocyte antioxidant enzyme activities, plasma TRAP, or vitamin levels was observed in subjects with the GSTM1 or GSTT1 genotypes, except ${\beta}$-carotene. Significant negative correlations were observed between lymphocyte DNA damage and plasma levels of TRAP and erythrocyte activities of catalase and GSH-Px after adjusting for smoking pack-years. Negative correlations were observed between plasma vitamin C and lymphocyte DNA damage only in individuals with the GSTM1-present or GSTT1- genotype. The interesting finding was the significant positive correlations between lymphocyte DNA damage and plasma levels of ${\alpha}$-carotene, ${\beta}$-carotene, and cryptoxanthin. In conclusion, the GSTM1- and GSTT1-present genotypes as well as smoking aggravated antioxidant status through lymphocyte DNA damage. This finding confirms that GST polymorphisms could be important determinants of antioxidant status in young smoking and non-smoking adults. Consequently, the protective effect of supplemental antioxidants on DNA damage in individuals carrying the GSTM1- or GSTT1-present genotypes might show significantly higher values than expected.