• The Journal of the Korea Contents Association
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• v.17 no.7
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• pp.648-663
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• 2017

To verify the association between GSTM1/GSTT1 gene polymorphisms and susceptibility to autoimmune diseases in Asian population. 18 published reports cited in EMBASE, Google, KISS, MEDLINE and PubMed up to December 2015 were collected for a meta-analysis. The GSTM1/GSTT1 polymorphism for null and present type were analysed separately. The significant association was found between the GST polymorphism and autoimmune diseases in an overall population (GSTM1, OR=1.334, 95% CI=1.137-1.567, p=0.000; GSTT1, OR=1.212, 95% CI=1.012-1.452, p=0.037). Asian population showed the significant association of GSTM1 in the autoimmune diseases, especially vitiligo and atopic dermatitis but non-significant association of GSTT1 in RA and SLE. The GSTM1 null and the GSTT1 present type showed the association with autoimmune diseases in Asian population. The null type frequency of the combination of GSTM1-GSTT1 polymorphism in autoimmune diseases in Asian population was higher than that of the control group. This result indicated that null type of GSTM1-GSTT1 combination can be a risk factor of autoimmune diseases in Asian population.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.7
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• pp.3325-3328
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• 2012

Aim: To evaluate the association of glutathione S-transferases gene polymorphisms with the risk of gastric cancer, with reference to smoking and Helicobacter pylori infection. Methods: We conducted a 1:1 matched case-control study with 410 gastric cancer cases and 410 cancer-free controls. Polymorphisms of GSTM1, GSTT1 and GSTP1 were determined using PCR-CTPP. Results: The GSTM1 and GSTT1 null genotypes were significantly associated with the risk of gastric cancer after adjusting for potential confounding factors (OR=1.68, 95% CI=1.32-2.23 for null GSTM1, OR=1.73; 95% CI=1.24-2.13 for null GSTT1). The combination of null GSTM1 and null GSTT1 conferred an elevated risk (OR=2.54, 95% CI=1.55-3.39). However, no association was found for GSTP1 polymorphism The smoking modified the association of GSTM1 and GSTT1 null genotypes with the risk of gastric cancer. Conclusion: GSTM1 and GSTT1 null genotypes are associated with increased risk of gastric cancer, and smoking modifies the association.

• 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.

• 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.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.3
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• pp.1141-1148
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• 2016

Background: A large number of studies have been published to investigate the association between the null genotype of glutathione S-transferase T1 (GSTT1) with gastric cancer. However, the results were inconsistent and conflicting. The aim of this study was to estimate the relationship between this polymorphism in the GSTT1 gene and gastric cancer risk in Asian populations by meta-analysis. Materials and Methods: A literature search was performed in PubMed, Embase, Chinese Biomedical database (CBM), Weipu database, Wanfang database, and China National Knowledge Infrastructure database (CNKI). Statistical analysis was conducted by using Review Manager 5.3. Results: Thirty-nine studies with a total of 7,737 gastric cancer cases and 10,823 controls were included in this meta-analysis. The meta-analysis of total studies showed that the null genotype in GSTT1 was associated with increased risk of gastric cancer in Asians (OR=1.19, 95% CI=1.08-1.31, p=0.0002). Subgroup analysis showed a significant relationship between GSTT1 null genotype and gastric cancer in East-Asians, as well as in subgroup analysis of hospital-based design. On subgroup analysis by smoking status, alcohol status, Helicobacter pylori infection status, and histology type, no significant association of this polymorphism with susceptibility to gastric cancer was found. Conclusions: In conclusion, the results showed that the null genotype of GSTT1 is significantly associated with an increased risk in gastric cancer in Asian populations.

• Clinical and Experimental Pediatrics
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• v.51 no.3
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• pp.262-266
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• 2008

Purpose : Glutathione S-transferase (GST) is a polymorphic supergene family of detoxification enzymes that are involved in the metabolism of numerous diseases. Several allelic variants of GSTs show impaired enzyme activity and are suspected to increase the susceptibility to diseases. Bilirubin is bound efficiently by GST members. The most commonly expressed gene in the liver is GSTM1, and GSTT1 is expressed predominantly in the liver and kidneys. To ascertain the relationship between GST and neonatal hyperbilirubinemia, the distribution of the polymorphisms of GSTT1 and GSTM1 were investigated in this study. Methods : Genomic DNA was isolated from 88 patients and 186 healthy controls. The genotypes were analyzed by polymerase chain reaction (PCR). Results : The overall frequency of the GSTM1 null was lower in patients compared to controls (P=0.0187, Odds ratio (OR) =0.52, 95% confidence interval (CI), 0.31-0.88). Also, the GSTT1 null was lower in patients compared to controls (P=0.0014, OR=0.41, 95% CI=0.24-0.70). Moreover, the frequency of the null type of both, in the combination of GSTM1 and GSTT1, was significantly reduced in jaundiced patients (P=0.0008, OR=0.31, 95% CI=0.17-0.61). Conclusion : We hypothesized that GSTM1 and GSTT1 might be associated with neonatal hyperbilirubinemia. However, the GSTT1 and GSTM1 null type was reduced in patients. Therefore the null GSTT1, null GSTM1, and null type of both in the combination of GSTM1 and GSTT1 may be not a risk factor of neonatal jaundice.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.10
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• pp.4967-4971
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• 2012

Background/Aims: Glutathione S-transferase T1 (GSTT1), a phase-II enzyme, plays an important role in detoxification of carcinogen electrophiles. Many studies have investigated the association between GSTT1 polymorphism and esophageal cancer risk in Asian populations, but its actual impact is not clear owing to apparent inconsistencies among those studies. Thus, a meta-analysis was performed to explore the effect of GSTT1 polymorphism on the risk of developing esophageal cancer. Methods: A literature search of PubMed, Embase, and Wanfang databases up to August 2012 was conducted and 15 eligible papers were finally selected, involving a total of 1,626 esophageal cancer cases and 2,216 controls. We used the pooled odds ratio (OR) with its corresponding 95% confidence interval (95%CI) to estimate the association of GSTT1 polymorphism with esophageal cancer risk. Subgroup analyses and sensitivity analyses were performed to further identify the association. Results: Meta-analysis of total studies showed the null genotype of GSTT1 was significantly associated with an increased risk of esophageal cancer in Asians (OR=1.26, 95%CI=1.05-1.52, $P_{OR}=0.015$, $I^2=42.7%$). Subgroup analyses by sample size and countries also identified a significant association. Sensitivity analysis further demonstrated a relationship of GSTT1 polymorphism to esophageal cancer risk in Asians. Conclusions: The present meta-analysis of available data showed a significant association between the null genotype of GSTT1 and an increased risk of esophageal cancer in Asians, particularly in China.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.8
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• pp.4739-4742
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• 2013

Carboplatin, a second generation platinum drug, is widely used to treat different types of cancers. However, myelosuppression remains a major consideration in its use. Genetic polymorphisms of enzymes involved in drug disposition can influence therapeutic outcome. The homozygous null deletion of phase II metabolic gene GSTT1 that abolishes its xenobiotic- detoxifying ability may be associated with carboplatin toxicity. Further, since carboplatin generates oxidative stress, polymorphisms of oxidative stress genes that regulate the cellular level of free radicals may have important roles in generating drug- related adverse effects. We here investigated the null polymorphism of GSTT1, and the -463G>A promoter polymorphism of oxidative stress gene myeloperoxidase (MPO) for carboplatin toxicity in a population of northern India. Cancer patients who were treated with carboplatin, and developed toxicity was considered. The study group comprised of 10 patients who developed therapy- related adverse effects. Peripheral blood was taken from patients for DNA isolation. GSTT1 null genotype was determined by conducting duplex PCR and MPO-463 G>A was determined by PCR followed by RFLP. Hematologic toxicity was experienced by 5 patients, 2 of them had grade 3 and 4 toxicity and 3 others had grade 2 toxicity. They also had gastrointestinal (GI) toxicity. Remaining 5 individuals developed GI toxicity but no hematological toxicity. While GG homozygous of MPO was present in majority of patients having hematologic toxicity (in 4 out of 5 individuals), one A allele (AG genotype) was present in 4 patients who did not have any hematological toxicity. Thus variant A allele of MPO -463G>A may be related to lower hematological toxicity. These preliminary data, however, are required to be confirmed in larger studies along with other relevant polymorphisms.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.5
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• pp.3345-3349
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• 2013

Background: Susceptibility to lung cancer has been shown to be modulated by inheritance of polymorphic genes encoding cytochrome P450 1A1 (CYP1A1) and glutathione S transferases (GSTM1 and GSTT1), which are involved in the bioactivation and detoxification of environmental toxins. This might be a factor in the variation in lung cancer incidence with ethnicity. Materials and Methods: We conducted a case-control study of 218 northern Indian lung cancer patients along with 238 healthy controls, to assess any association between CYP1A1, GSTM1 and GSTT1 polymorphisms, either separately or in combination, with the likelihood of development of Lung cancer in our population. Results: We observed a significant difference in the GSTT1 null deletion frequency in this population when compared with other populations (OR=1.87, 95%CI: 1.25-2.80-0.73, P=0.002). However, GSTM1 null genotype was found associated with lung cancer in the non-smoking subgroup. (P=0.170). Conclusions: Our study showed the GSTT1 null polymorphism to be associated with smoking-induced lung cancer and the GSTM1 null polymorphism to have a link with non-smoking related lung cancer.

• 대한임상약리학회:학술대회논문집
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• 2006.11a
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• pp.87-87
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• 2006