• Asian Pacific Journal of Cancer Prevention
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• v.13 no.7
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• pp.3109-3112
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• 2012

Background: Many studies have focused on possible associations between the glutathione S-transferase M 1 (GSTM1) null genotype and risk of renal cell carcinoma (RCC), but the impact remains unclear owing to obvious inconsistencies among the findings. The present study aimed to quantify the strength of any association in a meta-analysis. Methods: We searched the PubMed, Embase and CBM databases for studies concerning the association between the GSTM1 null genotype and risk of RCC. We estimated the summary odds ratio (OR) with its 95% confidence intervals (95% CI) to assess the association. Results: The meta-analysis showed the GSTM1 null genotype was not associated with risk of RCC overall (OR = 1.04, 95% CI 0.92-1.18, P = 0.501). For Caucasians, the GSTM1 null genotype was also not associated with risk of RCC (OR=1.02, 95% CI 0.90-1.16, P = 0.761). The cumulative meta-analyses showed a trend of no obvious association between GSTM1 null genotype and risk of RCC as information accumulated. Sensitivity analyses by omitting those studies also did not materially alter the overall combined ORs. No evidence of publication bias was observed. Conclusion: Meta-analyses of available data show that the GSTM1 null genotype is not significantly associated with risk of renal cell carcinoma.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.1
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• pp.355-361
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• 2015

Background: Deletion types of genetic variants of glutathione S-transferase (GST) M1 and T1, the GSTM1 null and GSTT1 null which are risk factors for certain cancers, have been ubiquitously found in human populations but their worldwide distribution pattern is unclear. Materials and Methods: To perform a meta-analysis, a systematic search for the literature on GSTM1 and GSTT1 null genotypes was done to identify 63 reports for 81 human populations. Relationships between the GSTM1 and GSTT1 null genotype frequencies and the absolute latitude of 81 populations were tested by Spearman's rank correlation coefficient. Results: A significant positive correlation was detected between the GSTM1 null genotype frequency and the absolute latitude (r=0.28, p-value <0.05), whereas the GSTT1 null genotype frequency and absolute latitude showed a significant negative correlation (r= -0.41 p-value <0.01). There was no correlation between the frequencies of GSTM1 and GSTT1 null genotype in each population (r= -0.029, p-value=0.80). Conclusions: Latitudinal clines of the distribution of the GSTM1 and GSTT1 null genotypes may be attributed to the result of gene-environmental adaptation. No functional compensation between GSTM1 and GSTT1 was suggested by the lack of correlation between the null frequencies for GSTM1 and GSTT1.

• 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.

• Nutrition Research and Practice
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• v.11 no.3
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• pp.214-222
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• 2017

BACKGROUND/OBJECTIVES: Glutathione S-transferase (GST) forms a multigene family of phase II detoxification enzymes which are involved in the detoxification of xenobiotics by conjugating substances with glutathione. The aim of this study is to assess the antioxidative status and the degree of DNA damage in the subclinical hypertensive patients in Korea using glutathione S-transferase polymorphisms. SUBJECTS/METHODS: We examined whether DNA damage and antioxidative status show a difference between GSTM1 or GSTT1 genotype in 227 newly diagnosed, untreated (systolic blood pressure $(BP){\geq}130mmHg$ or diastolic $BP{\geq}85mmHg$) subclinical hypertensive patients and 130 normotensive subjects (systolic BP < 120 mmHg and diastolic BP < 80 mmHg). From the blood of the subjects, the degree of the DNA damage in lymphocyte, the activities of erythrocyte superoxide dismutase, the catalase, and the glutathione peroxidase, the level of glutathione, plasma total radical-trapping antioxidant potential (TRAP), anti-oxidative vitamins, as well as plasma lipid profiles and conjugated diene (CD) were analyzed. RESULTS: Of the 227 subjects studied, 68.3% were GSTM1 null genotype and 66.5% were GSTT1 null genotype. GSTM1 null genotype had an increased risk of hypertension (OR: 2.104, CI: 1.38-3.35), but no significant association in GSTT1 null genotype (OR 0.982, CI: 0.62-1.55). No difference in erythrocyte activities of superoxide dismutase, catalase, or glutathione peroxidase, and plasma TRAP, CD, lipid profiles, and GSH levels were observed between GSTM1 or GSTT1 genotype. Plasma levels of ${\alpha}-tocopherol$ increased significantly in GSTT1 wild genotype (P < 0.05); however, plasma level of ${\beta}-carotene$ increased significantly in GSTT1 null genotype (P < 0.01). DNA damage assessed by the Comet assay was significantly higher in GSTM1 null genotype than wild genotype (P < 0.05). CONCLUSIONS: These results confirm the association between GSTM1 null genotype and risk of hypertension as they suggest that GSTM1 null genotype leads to an increased oxidative stress compared with wild genotype.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.3
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• pp.815-819
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• 2012

Aim: We conducted a meta-analysis to analyze the influence of GSTM1 and GSTT1 gene polymorphisms on cervical cancer risk, and explore gene-environment interactions. Methods: Identification of relevant studies was carried out through a search of Medline and the EMbase up to Oct. 2011. All case-control studies that investigated the association between GSTM1 and GSTT1 gene polymorphisms and risk of cervical cancer were included. The pooled odds ratio (OR) was used for analyses of results and the corresponding 95% confidence intervals (CI) were estimated. Results: A total of 21 case-control studies were included in the meta-analysis of GSTM1 (2,378 cases and 2,639 controls) and GSTT1 (1,229 cases and 1,223 controls) genotypes. The overall results showed that the GSTM1 null was related to an increased risk of cervical cancer (OR=1.50, 95% CI=1.21-1.85). Subgroup analysis were performed based on smoking and ethnicity. Our results showed that smokers with null GSTM1 genotype had a moderate increased risk of cervical cancer (OR=1.85, 95% CI=1.07-3.20). For the ethnicity stratification, moderate significantly increased risk of null GSTM1 genotype was found in Chinese (OR=2.12, 95% CI=1.43-3.15) and Indian populations (OR=2.07, 95% CI=1.49-2.88), but no increased risk was noted in others. Conclusion: This meta-analysis provided strong evidence that the GSTM1 genotype is associated with the development of cervical cancer, especially in smokers, and Chinese and Indian populations. However, no association was found for GSTT1 null genotype carriers.

• Korean Journal of Head & Neck Oncology
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• v.18 no.2
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• pp.150-156
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• 2002

Objectives: Most of human cancers may result from exposure to environmental carcinogens, and individual effectiveness in the detoxification of these chemicals will influence susceptibility to malignant disease. Glutathione S-Transferases(GSTs) enzymes are involved in the detoxification of active metabolites of many carcinogens from tobacco smoke and may be important in modulating susceptibility to smoke-related cancer. The purpose of this study is to determine the polymorphism of GSTM1, GSTT1, and GSTP1 in control group and head and neck squamous cell carcinoma group of Korean, and to investigate the effect of GSTs polymorphism on the risk of head and neck cancer. Materials and Methods: A hospital-based case-control study was performed with a group of 133 control individual and 136 head and neck squamous cell carcinoma patients. The polymorphisms of GSTs were analysed using polymerase chain reaction in GSTM1 and GSTTl, and polymerase chain reaction-restriction fragment length polymorphism in GSTP1. Results: The relative risk (odds ratio) of GSTM(-) genotype was 1.14(95% CI, 0.70-1.85) compared to GSTM1(+). The odds ratio of GSTTl(-) genotype was 0.91(95% CI, 0.55-1.50). In old age($65$) group, the odds ratio of GSTT1(-) genotype was 5.2(95% CI, 1.53-17.89). The GSTP1 Val/Val genotype conferred a 1.7-fold risk(95% CI, 0.40-7.34) of head and neck cancer compared with GSTP1 Ile/Ile genotype. Among the combined genotypes of GSTs, GSTM1(-)/GSTT1(+)/GSTP1 Val/Val and GSTM1(-)/GSTTl(-)/GSTP1 Ile/Val genotypes conferred a 2.6-fold and 1.3-fold risk(95% CI, 0.24-14.15 and 0.43-3.14) compared with the GSTM1(+)/GSTTl(+)/GSTP1 Ile/Ile genotype, respectively. Conclusion: Polymorphism of GSTs might modulate susceptibility to head and neck cancer in Korean population. The genotype of GSTP1 Val/Val and combined genotypes of GSTM1(-)/GSTT1(+)/GSTP1 Val/Val, and GSTM1(-)/GSTT1(-)/GSTP1 Ile/Val might be important risk factors to determine the individual susceptibility to head and neck squamous cell carcinoma.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.7
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• pp.3247-3252
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• 2012

Aim: We conducted a prospective study in an Chinese population to detect associations of GSTM, GSTT and GSTP polymorphisms with hepatocellular carcinoma (HCC), and analyze roles in determining survival outcome. Methods: A prospective follow-up study was conducted with 476 HCC patients and 481 controls collected from May 2005 to May 2007. All patients were followed up until the end of Dec. 2011. GSTM1, GSTT1 and GSTP1 genotyping were performed by PCR-CTPP methods. Results: Null GSTM1 carriers had a 1.64 fold risk of HCC compared with non-null genotype, while GSTP1 Val/Val carriers had a 93% increased risk over the GSTP1 IIe/IIe genotype. The median follow-up time for the 476 patients was 34.2 months (range: 1 to 78 months). Individuals with null GSTM1 genotype had better survival of HCC than non-null genotype carriers (HR=0.71, 95%CI=0.45-0.95). Similarly, GSTP1 Val/Val genotypes had significant better survival than the GSTP1 IIe/IIe genotype (HR=0.34, 95%CI=0.18-0.65). Individuals carrying null GSTM1 and GSTP1 Val/Val who received chemotherapy had lower risk of death from HCC than those without chemotherapy. Conclusion: This study indicated carriage of null GSTM1 and GSTP1 Val/Val genotypes to have roles in susceptibility to and survival from HCC.

• Journal of Nutrition and Health
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• v.44 no.1
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• pp.16-28
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• 2011

Oxidative stress leads to the induction of cellular oxidative damage, which may cause adverse modifications of DNA, proteins, and lipids. The production of reactive species during oxidative stress contributes to the pathogenesis of many diseases. Antioxidant defenses can neutralize reactive oxygen species and protect against oxidative damage. The aim of this study was to assess the antioxidant status and the degree of DNA damage in Korean young adults using glutathione s-transferase (GST) polymorphisms. The GSTM1 and GSTT1 genotypes were characterized in 245 healthy young adults by smoking status, and their oxidative DNA damage in lymphocytes and antioxidant status were assessed by GST genotype. General characteristics were investigated by simple questionnaire. From the blood of the subjects, GST genotypes; degree of DNA damage in lymphocytes; the erythrocyte activities of superoxide dismutase, catalase, and glutathione peroxidase; plasma concentrations of total peroxyl radical-trapping potential (TRAP), vitamin C, ${\alpha}$- and ${\gamma}$-tocopherol, ${\alpha}$- and ${\beta}$-carotene and cryptoxanthin, as well as plasma lipid profiles, conjugated diene (CD), GOT, and GPT were analyzed. Of the 245 subjects studied, 23.2% were GSTM1 wild genotypes and 33.4% were GSTT1 wild genotype. No difference in erythrocyte activities of superoxide dismutase, catalase, or glutathione peroxidase, and the plasma TRAP level, CD, GOT, and GPT levels were observed between smokers and non-smokers categorized by GSTM1 or GSTT1 genotype. Plasma levels of ${\alpha}$- and ${\gamma}$-tocopherol increased significantly in smokers with the GSTT1 wild genotype (p < 0.05); however, plasma level of ${\alpha}$-carotene decreased significantly in non-smokers with the GSTM1 wild genotype (p < 0.05). DNA damage assessed by the Comet assay was significantly higher in non-smokers with the GSTM1 genotype; whereas DNA damage was significantly lower in non-smokers with the GSTT1 genotype. Total cholesterol and LDL cholesterol levels were significantly higher in non-smokers with the GSTT1 genotype than those with the GSTT1 wild genotype (p < 0.05). In conclusion, the GSTM1 genotype or the GSTT1 wild genotype in non-smokers aggravated their antioxidant status through DNA damage of lymphocytes; however, the GSTT1 wild type in non-smokers had normal plasma total cholesterol and LDL-cholesterol levels. This finding confirms that GST polymorphisms could be an important determinant of antioxidant status and plasma lipid profiles in non-smoking young adults. Further study is necessary to clarify the antioxidant status and/or lipid profiles of smokers with the GST polymorphism and to conduct a study with significantly more subjects.

• 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.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.7
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• pp.3201-3205
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• 2014

The aim of this study was to investigate the frequencies of GSTT1 and GSTM1 deletion polymorphisms in newly-diagnosed patients with uterine cervical lesions from central Serbia. Polymorphisms of GST genes were genotyped in 97 patients with cervical lesions and 50 healthy women using a multiplex polymerase chain reaction (PCR). The GSTM1 null genotype was significantly more prominent among the patients than in controls (74.2% vs 56.0%), the risk associated with lesions being almost 2.3-fold increased (OR=2.26, 95%CI=1.10-4.65, p=0.03) and 3.17-fold higher in patients above >45 years old (95%CI=1.02-9.79, p=0.04). The analysis of the two genotypes demonstrated that GSTM1 null genotype significantly increased risk only for low grade squamous intraepithelial lesion-LSIL (OR=2.81, 95%CI=1.03-7.68, p=0.04). GSTT1 null genotype or different genotype combinations were not found to be risk factors, irrespective to lesion stages, age or smoking. We found that the risk of cervical lesions might be significantly related to the GSTM1 null genotype, especially in women aged above 45 years. Furthermore, the GSTM1 polymorphism might have greater role in development of early stage lesions.