Association of glutathione S-transferase M1 and T1 null polymorphisms with the development of cervical lesions: a meta-analysis.
ABSTRACT An accumulation of evidence suggests that gene-based self-susceptibility may contribute to the development of cancer. Some studies have found that particular polymorphisms of the glutathione S-transferase M1 and T1 genes are associated with increased risk of cervical lesions, but other studies have had contrary results. The present meta-analysis evaluated the association of glutathione S-transferase M1 and T1 null polymorphisms with the development of cervical lesions. In addition, stratified analyses were performed in an attempt to identify any race-specific effects.
Twenty-one related studies were included in the meta-analysis, comprising glutathione S-transferase M1 data from 1423 patients with cervical lesions and 2415 healthy matched controls, and glutathione S-transferase T1 data from 2081 patients with cervical lesions and 2287 healthy matched controls. The fixed-effect model (Mantel-Haenszel method) and the random-effect (DerSimonian and Laird) model were used to examine the difference in frequency of glutathione S-transferase M1 and T1 null polymorphisms between pre- and invasive cervical lesions. Subgroup analyses were also conducted to evaluate any race-specific effect on the frequencies of glutathione S-transferase polymorphisms in cervical lesions. Odds ratios (OR) and 95% confidence intervals (CI) were calculated. Heterogeneity was assessed using the heterogeneity metric (I²) and Chi-squared test.
The glutathione S-transferase M1 null polymorphism was associated with increased risk of low-grade intra-epithelial lesions (OR 1.37, 95% CI 1.05-1.77), but no increased risk of high-grade intra-epithelial lesions (OR 1.29, 95% CI 0.87-1.8) or invasive cervical cancer (OR 1.20, 95% CI 0.99-1.46). The association seemed to be confined to Southeast Asians (OR 1.97, 95% CI 1.44-2.71). No significant associations were found for the glutathione S-transferase T1 null polymorphism for any of the populations.
The glutathione S-transferase M1 null polymorphism significantly increases susceptibility to early-stage cervical lesions in Southeast Asians. However, the glutathione S-transferase T1 null polymorphism does not appear to be a risk factor for cervical lesions in any population.
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ABSTRACT: The association of the three Glutathione S-transferases (GSTs) polymorphisms (GSTM1, GSTT1 and GSTP1) genotypes with their individual susceptibilities to renal cell carcinoma (RCC) has not been well established. We performed a quantitative meta-analysis to assess the possible associations between the GSTM1, GSTT1 and GSTP1 genotypes and their individual susceptibilities to renal cell carcinoma. We systematically searched the PubMed, CNKI and Embase databases to identify the relevant studies. Finally, 11 eligible studies were selected. The pooled odds ratios (ORs) with their 95% confidence intervals (CIs) were used to assess the association between the GSTs polymorphisms and the risk of RCC. Multiple subgroup analyses and quality assessment of the included studies were performed based on the available information. None of the GSTs polymorphisms had a significant association with the RCC risk. Similar results were found in the subgroup analyses, except for the GSTs polymorphisms in the situations described below. The GSTM1 and GSTT1 active genotypes in subjects exposed to pesticides (GSTM1: OR = 3.44; 95% CI, 2.04-5.80; GSTT1: OR = 2.84; 95% CI, 1.75-4.60), most of the GSTs genotypes in Asian populations (GSTT1: OR = 2.39, 95% CI = 1.63-3.51; GSTP1: Dominant model: OR = 1.50, 95% CI = 1.14-1.99; Additive model: OR = 1.39, 95% CI = 1.12-1.73; AG vs. AA: OR = 1.47, 95% CI = 1.10-1.97; GG vs. AA: OR = 1.82, 95% CI = 1.07-3.09) and the dual null genotype of GSTT1-GSTP1 (OR = 2.84, 95% CI = 1.75-4.60) showed positive associations with the RCC risk. Our present study provides evidence that the GSTM1, GSTT1 and GSTP1 polymorphisms are not associated with the development of RCC. However, more case-control studies are needed for further confirmation.PLoS ONE 01/2013; 8(5):e63827. · 3.53 Impact Factor
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ABSTRACT: CD95 is the first death receptor identified and characterized in recent years, and it plays important roles in the molecular network regulating cell death and survival. CD95 rs1800682 polymorphism is a common genetic polymorphism identified in the CD95 gene. Many publications evaluated the association between CD95 rs1800682 polymorphism and cervical cancer risk, but the association remained inconclusive. To provide a more precise estimate on the association, a meta-analysis was carried out. The association between CD95 rs1800682 polymorphism and cervical cancer risk was assessed by calculating the pooled odds ratio (OR) with its 95 % confidence intervals (95 % CI). On the basis of our inclusion criteria, ten studies with a total of 5,481 individuals were included into the meta-analysis. There was obvious heterogeneity among the included studies. Meta-analysis of the ten studies suggested that there was no association between CD95 rs1800682 polymorphism and cervical cancer risk under all four genetic models (allele model: OR = 1.05, 95 % CI 0.92-1.18, P = 0.478; homozygous model: OR = 1.08, 95 % CI 0.83-1.41, P = 0.550; dominant model: OR = 1.12, 95 % CI 0.88-1.42, P = 0.347; recessive model: OR = 1.00, 95 % CI 0.76-1.31, P = 0.978). Subgroup analysis by ethnicity suggested that there was no association between CD95 rs1800682 polymorphism and cervical cancer risk in Asians, Caucasians, and Africans. Thus, the meta-analysis suggests that CD95 rs1800682 polymorphism is not associated with cervical cancer risk.Tumor Biology 10/2013; · 2.52 Impact Factor
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ABSTRACT: Oxidative stress is increased in chronic kidney disease, owing to an imbalance between the oxidative and antioxidant pathways as well as a state of persistent hyperhomocysteinemia. The enzymes glutathione S-transferases (GSTs) and methylenetetrahydrofolate reductase (MTHFR) are implicated in the regulation of these pathways. This study investigates the association between polymorphisms in the Glutathione S-transferase Mu 1 (GSTM1), glutathione S-transferase theta 1 (GSTT1), and MTHFR genes and end-stage renal disease (ESRD) of unknown etiology in patients in Mexico. A Case-control study included 110 ESRD patients and 125 healthy individuals. GSTM1 and GSTT1 genotypes were determined using the multiplex polymerase chain reaction (PCR). The MTHFR C677T polymorphism was studied using a PCR/restriction fragment length polymorphism method. In ESRD patients, GSTM1 and GSTT1 null genotype frequencies were 61% and 7% respectively. GSTM1 genotype frequencies differed significantly between groups, showing that homozygous deletion of the GSTM1 gene was associated with susceptibility to ESRD of unknown etiology (P = 0.007, odds ratios = 2.05, 95% confidence interval 1.21-3.45). The MTHFR C677T polymorphism genotype and allele distributions were similar in both groups (P > 0.05), and the CT genotype was the most common genotype in both groups (45.5% and 46.6%). Our findings suggest that the GSTM1 null polymorphism appears to be associated with the ESRD of unknown etiology in patients in Mexico.Indian Journal of Nephrology 11/2013; 23(6):438-43.