Association among Serum Organochlorine Pesticide Residues, Glutathione S-Transferase M1 Genetic Polymorphism and Female Breast Cancer

Background: The purpose of this study was to evaluate the association among serum organochlorine pesticide residues, glutathione S-transferase M1 genetic polymorphism and female breast cancer. Methods: A 1:1 matched case-control study of 140 newly diagnosed breast cancer patients and 140 non-cancer female patients who consulted the five largest hospitals in the Tangshan city from September 2006 to October 2007. Results: The result showed higher risk of breast cancer among subjects with higher levels of serum DDT and HCH residue, the OR was 3.18 (95%CI, 1.11 - 9.07) and 5.02 (95%CI, 1.64 - 16.56).The value of ORe associated with single environmental factor DDT high residues, and ORg associated with single GSTM1 deletion genotype were respectively 3.86 (1.20 - 12.47) and 1.34 (0.36 - 5.08). The OReg associated with combined action of two factors was 5.59 (1.63 - 18.90), and the value of interaction parameters (γ) equaled 1.24. The value of ORe associated with single environmental factor HCH higher residue and ORg associated with single GSTM1 deletion genotype were respectively 2.73 (0.84 - 8.87) and 1.48 (0.49 - 4.60). The value of OReg associated with combined action of two factors was 3.87 (1.18 - 12.68), and γ equaled 1.38. Conclusion: The results indicated that breast cancer occurrence was the combined result of environmental and genetic factors. The concurrent action of GSTM1 deletion genotype and DDT/HCH enhanced the risk of breast cancer.

Glutathione S-transferase M1 and T1 Gene Deletion Associated with Increased Susceptibility to Nasopharyngeal Carcinoma

Objective： To evaluate the association of Glutathione S-transferase （GST） M1 and T1 genetic polymorphisms and susceptibility to nasopharyngeal carcinoma （NPC） in a high risk area of Guangxi Zhuang Autonomous Region （province）, Southwest of China. Methods： A case-control study was conducted to investigate the genetic polymorphisms of these enzymes （GSTM1 and GSTT1 null genotypes）. A total of 127 NPC cases and 207 controls were recruited. Results： GSTM1 and GSTT1 null genotype frequencies were higher among NPC patients at a level of statistical significance （P〈0.005; P〈0.001 respectively）, and both GSTM1 and GSTT1 null genotype were even more significant （P〈0.001）. Conclusion： NPC is the most common cancer in Guangxi. GST enzymes are involved in the detoxification of many environmental carcinogens. Homozygous deletions of GSTM1 and GSTT1 have been associated with several types of cancer. The risk to develop NPC has been associated with environmental factors such as cigarette smoking and EB virus infection. The present results indicate that the GSTM1 and GSTT1 deletion polymorphisms are associated with an increase risk of susceptibility to NPC, and both detoxific enzyme genes deletion is more important than a single gene deletion for the susceptibility to NPC.

Association of glutathione S-transferase T1 and M1 gene polymorphisms with ischemic stroke risk in the Chinese Han population

Atherosclerosis plays an important role in ischemic stroke, and oxidative stress participates in the entire process of atherosclerosis. Glutathione S-transferase （GST） acting with other antioxidant enzymes can eliminate reactive oxygen species and protect cells against oxidative damage. To assess the association of glutathione S-transferase （GSTT1 and GSTM1） gene polymorphisms with ischemic stroke in the Chinese Han population, the present study selected 315 patients with ischemic stroke and 210 healthy controls for comparison. GSTT1 and GSTM1 genotypes were determined using polymerase chain reactions, electrophoresis and imaging analysis. No obvious evidence of GSTTI-nulI, GSTMI-null and GSTTI/GSTMI-double null genotype distribution differences was found between case and control groups or between genders. Subgroup analysis showed that the risk of stroke was increased when hypertension was accompanied by GSTTl-null （odds ratio （OR） = 2.996, P 〈 0.001） and GSTMl-null （OR = 3.680, P 〈 0.001 ） genotypes; diabetes mellitus was accompanied by GSTTI-null （OR = 1.860, P = 0.031） and GSTMI-null （OR = 2.444, P = 0.002） genotypes, and smokers showed a GSTTl-null genotype （OR = 2.276, P = 0.003）. GSTT1- and GSTMl-null genotypes may interact synergistically with hypertension, diabetes mellitus and smoking to increase the incidence risk of ischemic stroke.

Anticancer Drug Resistance of HeLa Cells Transfected With Rat Glutathione S-transferase pi Gene

To establish a cytologic expressing system of rat glutathione S-transferase pi (GST-pi) cDNA for detecting the resistance of HeLa cells to anticancer drugs. Methods The assessment was made with various anticancer drugs (adriamycin, mitomycin, cisplatinum and vincristine) that showed different cytotoxicities in transfectant HeLa cells with pSV-GT containing rat GST-pi cDNA (HeLa/pSV-GT) or control pSV-neo (HeLa/pSV-neo). Expression levels of GST-pi mRNA in HeLa/pSV-GT and HeLa/pSV-neo were measured by in situ hybridization using Digoxin-labelled cDNA probe. Results HeLa/pSV-GT expressed significantly high degree of GST-pi mRNA, whereas both HeLa/pSV-neo and HeLa cells had very low expression. Cytotoxicities of HeLa/pSV-GT and HeLa/pSV-neo with 4 anticancer drugs were measured by MTT assay. Drug concentrations for yielding 50% inhibition (IC50) in HeLa/pSV-GT by adriamycin, mitomycin and cisplatinum were 70.13 靏/mL, 10.95 靏/mL and 16.52 靏/mL, respectively. In contrast, IC50 in HeLa/pSV-neo was 10.34 靏/mL, 7.48 靏/mL and 13.70 靏/mL, respectively. The cytotoxicities of vincristine on both HeLa/pSV-GT and HeLa/pSV-neo were not significantly different. Conclusions Our findings suggest that HeLa/pSV-GT containing rat GST-pi cDNA is resistant to some anticancer drugs due to overexpression of GST-pi. Also, HeLa/pSV-GT cell line could serve as a useful cytogenetic model for further research.

Association between Polymorphisms of Glutathione S-Transferase and Progression to Cervical Cancer in Women from Burkina Faso and Mali

Although persistence of high-risk human papillomavirus infection is the main risk factor, Glutathione S-Transferase highly polymorphic enzyme involved in the metabolism of xenobiotics, is a good candidate gene. The objective of this study was to compare the polymorphisms of Glutathione S-Transferase M1-null in women with cancerous lesions and without lesions. This study consisted of 322 uterine cervix samples of women from Mali and Burkina Faso with Cervical Intra-epithelial Neoplasia 2 and 3, adenocarcinoma and squamous cell carcinoma and 100 women with no lesions. Human Papillomavirus genotyping was performed by Real-time multiplex Polymerase Chain Reaction. Glutathione S-Transferase gene polymorphisms were determined using conventional Polymerase Chain Reaction followed by migration on agarose gel. A statistically significant association with high relative risks of 10.77 for the development of High grade Superficial or Squamous Intra-epithelial Lesion (95% CI = 5.59 - 20.72;p < 0.001), and 13.20 for cancer development (95% CI = 6.79 - 25.63;p < 0.001) was found in women with the null genotype of Glutathione S-Transferase M1 in the study population. In Burkina Faso and Mali, Glutathione S-Transferase M1-null presented relative risks of 9 and 11.05 for high-grade lesions, 15 and 11.40 for cancer. Similarly, significant results had been observed in women with human papillomavirus positive and human papillomavirus negative. The results of the present study support the idea that the deletion of Glutathione S-Transferase M1 plays a crucial role in the progression of high-grade lesions and cervical cancer.

Effect of trans-acting factor on rat glutathione S-transferase P1 gene transcription regulation in tumor cells

Objective To investigate the effect of trans-acting factor(s) on rat glutathione S-transferase P1 gene (rGSTP1) transcription regulation in tumor cells.Methods The binding of trans-acting factor(s) to two enhancers of the rGSTP1 gene, glutathione S-transferase P enhancer Ⅰ (GPEI) and glutathione S-transferase P enhancer Ⅱ-1 (GPEⅡ-1), was identified by an electrophoretic mobility shift assay (EMSA). The molecular weight of trans-acting factor was measured in a UV cross-linking experiment. Results Trans-acting factor interacting with the core sequence of GPEI (cGPEI) were found in human cervical adenocarcinoma cell line (HeLa) and rat hepatoma cell line (CBRH7919). These proteins were not expressed in normal rat liver. Although specific binding proteins that bound to GPEⅡ-1 were detected in all three cell types, a 64 kDa binding protein that exists in HeLa and CBRH7919 cells was absent in normal rat liver. Conclusion cGPEI, GPEII specific binding proteins expressed in HeLa and CBRH7919 cells may play an important role in the high transcriptional level of the rGSTP1 gene in tumor cells.

Polymorphisms of GSTM1 and CYP1A1 genes and their genetic susceptibility to prostate cancer in Chinese men

Background Variation in prostate cancer incidence between different racial groups has been well documented, for which genetic polymorphisms are hypothesized to be an explanation. We evaluated the association between polymorphisms in the cytochrome P-450 CYP1A1 （CYP1A1） and glutathione S-transferase M1 （GSTM1） genes and genetic susceptibility to prostate cancer in Chinese men.Methods TWO hundred and eight prostate cancer patients and 230 age matched controls were enrolled in this study. All DNA samples from peripheral blood lymphocytes were genotyped for common genetic polymorphisms of the CYP1A1 and GSTM1 genes using the oligonucleotide microarray （DNA chip） technique and the polymorphism results confirmed by sequencing. The different polymorphisms in prostate cancer patients were also analyzed according to age at diagnosis, prostate specific antigen level, cancer stage and grade （Gleason score）.Results The prevalence of the GSTM1 （0/0） genotype was significantly higher in prostate cancer patients （58.2%） than in controls （41.7%, P〈0.05）. Further analysis demonstrated that the prostate cancer patients with a GSTM1 （0/0） genotype were younger than those with the GSTM1 （＋/＋） genotype （P=-0.024）. No significant differences in the frequency distributions of CYP1A1 polymorphisms were observed between prostate cancer patients and controls.Conclusion GSTM1 （0/0）-gene polymorphism may be linked to prostate cancer risk and early age of Onset in Chinese.