• Title/Summary/Keyword: GSTP

Search Result 56, Processing Time 0.026 seconds

Increased Hypermethylation of Glutathione S-Transferase P1, DNA-Binding Protein Inhibitor, Death Associated Protein Kinase and Paired Box Protein-5 Genes in Triple-Negative Breast Cancer Saudi Females

  • Hafez, Mohamed M.;Al-Shabanah, Othman A.;Al-Rejaie, Salim S.;Al-Harbi, Naif O.;Hassan, Zeinab K.;Alsheikh, Abdulmalik;Theyab, Abdurrahman I. Al;Aldelemy, Meshan L.;Sayed-Ahmed, Mohamed M.
    • Asian Pacific Journal of Cancer Prevention
    • /
    • v.16 no.2
    • /
    • pp.541-549
    • /
    • 2015
  • Triple negative breast cancer (TNBC) is an aggressive subtype of breast cancer (BC) with higher metastatic rate and both local and systemic recurrence compared to non-TNBC. The generation of reactive oxygen species (ROS) secondary to oxidative stress is associated with DNA damage, chromosomal degradation and alterations of both hypermethylation and hypomethylation of DNA. This study concerns differential methylation of promoter regions in specific groups of genes in TNBC and non-TNBC Saudi females in an effort to understand whether epigenetic events might be involved in breast carcinogenesis, and whether they might be used as markers for Saudi BCs. Methylation of glutathione S-transferase P1 (GSTP1), T-cadherin (CDH13), Paired box protein 5 (PAX5), death associated protein kinase (DAPK), twist-related protein (TWIST), DNA-binding protein inhibitor (ID4), High In Normal-1 (HIN-1), cyclin-dependent kinase inhibitor 2A (p16), cyclin D2 and retinoic acid receptor-${\beta}$ ($RAR{\beta}1$) genes was analyzed by methylation specific polymerase chain reaction (MSP) in 200 archival formalin-fixed paraffin embedded BC tissues divided into 3 groups; benign breast tissues (20), TNBC (80) and non-TNBC (100). The relationships between methylation status, and clinical and pathological characteristics of patients and tumors were assessed. Higher frequencies of GSTP1, ID4, TWIST, DAPK, PAX5 and HIN-1 hypermethylation were found in TNBC than in non-TNBC. Hypermethylation of GSTP1, CDH13, ID4, DAPK, HIN-1 and PAX5 increased with tumor grade increasing. Other statistically significant correlations were identified with studied genes. Data from this study suggest that increased hypermethylation of GSTP1, ID4, TWIST, DAPK, PAX5 and HIN-1 genes in TNBC than in non-TNBC can act as useful biomarker for BCs in the Saudi population. The higher frequency of specific hypermethylated genes paralleling tumor grade, size and lymph node involvement suggests contributions to breast cancer initiation and progression.

The Relationship between the Polymorphism of CYP1A1, GSTM1, GSTT1, GSTP1 and p53 Overexpression in Head and Neck Squamous Cell Carcinoma (두경부 편평세포암종에서 CYP1A1, GSTM1, GSTT1, GSTP1 유전자 다형성 및 p53 과발현)

  • Tae Kyung;Park Hye-Kyung;Lee Seung-Hwan;Kim Kyung-Rae;Lee Hyung-Seok
    • Korean Journal of Head & Neck Oncology
    • /
    • v.19 no.2
    • /
    • pp.148-157
    • /
    • 2003
  • Background and Objectives: Individual genetic susceptibilities to chemical carcinogens have been recognized as a major important host factors in human cancers. The cytochrome P450 family (CYPs) and glutathione S-transferase(GST) have been reported to be associated with risks to the smoking-related human cancers. Inactivation of tumor suppressor genes like p53 playa key role in tumor progression. The purpose of this study is to demonstrate an association between p53 overexpression and the prevalence of the genetic polymorphisms of CYP1A1 and GSTs in Korean head and neck squamous cell carcinoma (HNSCC). Materials and Methods: The polymorphisms of CYPIA1 and GSTs were analyzed by PCR and PCR-RFLP in 98 Korean head and neck squamous cell carcinoma patients. The expression of p53 was analyzed by immunohistochemistry with anti-p53 Ab (DO7). Results: Overexpression of p53 detected in 45.9% of HNSCC. The odds ratio for p53 overexpression in GSTM1(-), GSTT1(-), GSTP1(val/val) and CYP1A1(val/val) were 1.53, 1.83, 1.17 and 1.47, respectively. Among the combined genotypes, the odds ratio of the CYP1A1 val/val, GSTM1 (-), CYP1A1 val/val, GSTT1(-), and CYP1A1 val/val, GSTT1(-) were 2.0, 2.34 and 4.68, respectively. Conclusion: Based on our results, it might be suggested that p53 overexpression is slightly increased in GSTM1(-), GSTT1(-), GSTP1 val/val, CYP1A1 val/val genotypes. The further study is needed to evaluate the relationship and mechanism between the p53 overexpression and the specific CYP1A1 and GSTs genotypes.

Risk Effects of GST Gene Polymorphisms in Patients with Acute Myeloid Leukemia: A Prospective Study

  • Zhou, Lei;Zhu, Yan-Yun;Zhang, Xiao-Dong;Li, Yang;Liu, Zhuo-Gang
    • Asian Pacific Journal of Cancer Prevention
    • /
    • v.14 no.6
    • /
    • pp.3861-3864
    • /
    • 2013
  • Glutathione S-transferase (GST) enzyme levels are associated with risk of many cancers, including hematologic tumours. We here aimed to investigate the relationships between GSTM1, GSTT1 and GSTP1 polymorphisms and the risk of AML. Genotyping of GSTs was based upon duplex polymerase-chain-reactions with the confronting-two-pair primer (PCR-CTPP) method in 163 cases and 204 controls. Individuals carrying null GSTT1 genotype had a 1.64 fold risk of acute leukemia relative to a non-null genotype (P<0.05). A heavy risk was observed in those carrying combination of null genotypes of GSTM1 and GSTT1 and GSTP1 Val allele genotypes when compared with those carrying wild genotypes, with an OR (95% CI) of 3.39 (1.26-9.26) (P<0.05). These findings indicate that genetic variants of GST and especially the GSTT1 gene have a critical function in the development of AML. Our study offers important insights into the molecular etiology of AML.

Predictive Role of Glutathione-S-transferase Gene Polymorphisms in the Survival of Gastric Cancer Cases

  • Wang, Zhao-Yang;Zhou, Jing;Luo, Li;Huang, Ying-Long;Dong, Pei-De
    • Asian Pacific Journal of Cancer Prevention
    • /
    • v.13 no.4
    • /
    • pp.1515-1518
    • /
    • 2012
  • Aim: We conducted a prospective study in an Chinese population to detect the association between GSTM, GSTT and GSTP gene polymorphisms and survival of gastric cancer. Methods: A prospective follow-up study with 317 gastric cancer patients was conducted between January 2003 and January 2005. GSTM1, GSTT1 and GSTP1 genotyping was performed using ABI TaqMan Gene Expression assays. Results: Of 317 patients, 5 were lost to follow-up due to migration, while the remaining 302 patients completed the study. The median follow-up time was 34.2 months (range: 2 to 60 months), during which a total of 120 (39.1%) died of gastric cancer. The GSTT1-null genotype showed a significant increased risk of death from gastric cancer, with an HR (95% CI) of 1.59 (1.04-3.58). Moreover, we found individuals carrying null-GSTM1 and null-GSTT1 had a moderate higher risk of death from gastric cancer, with an HR of 1.92 (1.05-3.65). Conclusion: This study reported the carriage of null GSTT1 and null GSTM1 might be linked to the higher death risk from gastric cancer in Chinese population.

Biomonitoring Human Exposure to VOCs : Using Individual Susceptibility Markers

  • Kim, Jung-Hyun;Kim, Dae-Seon;Park, Jae-Sung;Kang, Tack-Shin
    • Proceedings of the Korean Environmental Health Society Conference
    • /
    • 2003.06a
    • /
    • pp.187-191
    • /
    • 2003
  • In this study, biomonitoring methods were developed to measure BTEXs exposure level in the air, metabolites of benzene and toluene in human urine, individual susceptibility markers in human blood for evaluation of the health effects about environmental pollution. We have also performed a small-scaled molecular epidemiology study on residents in Chuncheon and workers in workplace for these method applications. The workers in workplace were surveyed as study areas, and the residents in Chuncheon which is in the suburban area were surveyed as comparative areas in this study. Actually, 31 workers in as target group and 33 residences in as control group this epidemiological study. The results obtained from this study were as follows: 1. Benzene is a well-known carcinogen, it's median concentrations were 0.00024∼0.02057ppm at suburban area and 0.002∼00.654ppm at work place, These benzene concentrations were not exceed the OSHA(Occupational Safety and Health Administration) threshold benzene level of 1ppm in the states. 2. Metabolites product of benzene(t,t-Muconic Acid) and toluene(Hippuric Acid) were not significant both in suburban and workplace area. The median concentration of t,t-MA and HA were 0.0122, 1.44277g/g creatinine, respectively. 3. In the case of individual susceptibility markers as CYPlAl, 41.8% of them has homozygous wild type(W) and who has heterozygous variant type(H) was 35.4% and 22.8% of homozygous variant type(M) genetic type. In the case of CYP2E1, 62.82% of them has homozygous wild type(D) type, 34.62% of each has heterozygous variant type (DC) and 2.56% of them has homozygous variant type (CC). Who doesn't have GSTM1 gene was 46.25% and who has GSTM1 gene was 53.75%. Who doesn't have GSTT1 gene was 40.0% in study groups and who has GSTT1 gene was 60.0%. Who has W genetic type, which is homozygous wild type of GSTP1, was 69.18% and H genetic type, which is heterozygous variant type was 28.4%. M genetic type which is homozygous variant type was 2.4%. 4. Concentration differences of metabolites such as t,t-MA and HA in urine, which is generated by individual susceptibility marker of GSTM1, GSTT1, GSTP1 gene of Phase I and CYP1A1, CYP2E1 gene of Phase II, was examined. As a result, GSTP1 and GSTM1 indicate slight differences depend on the amount of metabolites in urine, it was not statistically significant.

  • PDF

Susceptibility of Lung Cancer with Polymorphisms of CYP1A1, GSTM1, GSTM3, GSTT1 and GSTP1 Genotypes in the Population of Inner Mongolia Region

  • Jiang, Xue-Yan;Chang, Fu-Hou;Bai, Tu-Ya;Lv, Xiao-Li;Wang, Min-Jie;Wang, Guang
    • Asian Pacific Journal of Cancer Prevention
    • /
    • v.15 no.13
    • /
    • pp.5207-5214
    • /
    • 2014
  • Background: To study the relationship of susceptibility to lung cancer with the gene polymorphisms of CYP1A1, GSTM1, GSTM3, GSTT1, GSTP1 and smoking status in Han and Mongolian populations of Inner Mongolia, an autonomous region of China. Materials and Methods: PCR-RFLP, allele-specific and multiplex PCR were employed to identify the genotypes of CYP1A1, GSTM1, GSTM3, GSTT1 and GSTP1 in a case-control study of 322 lung cancer patients diagnosed by bronchoscopy and 456 controls free of malignancy. Results: There is a significant difference in genotypic frequency of GSTT1 of healthy Mongolian and Han subjects. A statistically prominent association was found between CYP1A1 Msp1 (vt/vt) (OR=4.055, 95%CI:2.107-7.578, p=0.000), GSTM1 (-) (OR=2.290, 95%CI:1.467-3.573, p=0.000) and lung cancer in Mongolians. Similarly, in the Han population, CYP1A1 Msp1 (vt/vt) (OR=3.194, 95%CI:1.893-5.390, p=0.000) and GSTM1 (-) (OR=1.884, 95%CI:1.284-2.762, p=0.001) carriers also had an elevated risk of lung cancer. The smokers were more susceptible to lung cancer 2.144 fold and 1.631 fold than non-smokers in Mongolian and Han populations, respectively. The smokers who carried with CYP1A1 Msp1 (wt/vt+vt/vt), exon7 (Val/Val+Ile /Val), GSTM1 (-), GSTM3 (AB+BB), and GSTT1 (-) respectively were found all to have a high risk of lung cancer. Conclusions: CYP1A1 Msp1 (vt/vt) and GSTM1 (-) are risk factors of lung cancer in Han and Mongolian population in the Inner Mongolia region. The smokers with CYP1A1 Msp1 (wt/vt+vt/vt), CYP1A1 exon7 (Val/Val+Ile /Val), GSTM1 (-), GSTM3 (AB+BB), and GSTT1 (-) genotypes, respectively, are at elevated risk of lung cancer.

Glutathione S-transferases (GSTM1, GSTT1 and GSTP1) and N-acetyltransferase 2 Polymorphisms and the Risk of Gastric Cancer (위암 환자에서 Glutathione S-transferases (GSTM1, GSTT1, GSTP1) 및 N-acetyltransferase 2 유전자 다형성 분포)

  • Hong, Su-Hyung;Kim, Jung-Wan;Kim, Ho-Gak;Park, In-Kyu;Ryoo, Jun-Wook;Lee, Chang-Hyeong;Sohn, Yoon-Kyung;Lee, Jong-Young
    • Journal of Preventive Medicine and Public Health
    • /
    • v.39 no.2
    • /
    • pp.135-140
    • /
    • 2006
  • Objectives : Polymorphisms of genes from glutathione Stransferases (GSTs) and N-acetyltransferase 2 (NAT2) have been associated with increased susceptibility to various cancers. Previous results showed that East Asians such as Koreans, Japanese and Chinese have a much higher frequency of the GSTM1 and GSTT1 null genotypes and NAT2 rapid acetylator type. Therefore, we investigated the association between the polymorphic types of GSTs (GSTM1, GSTT1, GSTP1) and NAT2 and the incidence of gastric cancer which is one of the most prevalent cancers among the East Asians. Methods : It was performed in a case-control study consisting of 238 healthy subjects and 108 cancer patients (54 distal and 54 proximal carcinomas). We also evaluated the association between GSTs and NAT2 and the risk factors for gastric cancer such as alcohol consumption, smoking, H. pylori infection, family history of gastric cancer, and tumor location. Results : In our study, the percentage of cases whose hometown was rural was higher than those of controls (odds ratio (OR) =2.88; 95% CI=1.72-4.76), and the frequency of the lower socio-economic status increased significantly in patients (OR=2.53; 95% CI=1.59-4.02). There was no significant difference in the GST polymorphic types between the cases and controls. However, NAT2 rapid or intermediate acetylator types were frequently detected in the cases with family history of gastric cancer (OR=1.92; 95% CI=1.79-26.0). Conclusions : These results suggest that the hometown and socio-economic status are important environmental factors for gastric carcinogenesis, and NAT2 polymorphic types could be associated with familial gastric carcinoma.