Abstract
Emerging evidences suggest that GSTM1 and GSTT1 are involved in the detoxification of carcinogens, and polymorphisms in this gene that result in a loss of enzyme activity may increase the risk of renal cell carcinoma (RCC). Thus, to evaluate the association of GSTM1 and GSTT1 polymorphisms and RCC, we performed an updated meta-analysis of 10 case-control studies by RevMan 5.2, and the publication bias was tested using STATA 11.0. The meta-analysis showed that the single locus GSTM1 and GSTT1 polymorphisms were not significantly associated with a risk of RCC in a recessive model. However, that wild-type genotype versus the dual null genotype of GSTM1-GSTT1 showed a positive association with RCC risk (OR = 0.70; 95% CI = 0.51–0.98; P = 0.04). In another analysis of subjects exposed to pesticides, we found that the GSTM1 wild-type genotype was associated with increased RCC risk in Europeans (OR = 2.72; 95% CI = 1.54–4.82; P = 0.0006). We also identified an association between the GSTT1 wild-type and lower RCC TNM staging (I + II versus III + IV: OR = 1.88; 95% CI = 1.09–3.26; P = 0.02). This meta-analysis suggests that there may be a relationship between the GSTM1 and GSTT1 wild-type genotype and RCC.
Highlights
This meta-analysis suggests that there may be a relationship between the GSTM1 and GSTT1 wild-type genotype and Renal cell carcinoma (RCC)
Three studies, all conducted in Europe, assessed the association between GSTM1 or GSTT1 and RCC in patients exposed to pesticide or trichloroethene, which both included 107 cases and 101 controls (Table 2)
In studies that assessed subjects exposed to pesticides, we found that GSTM1 wild-type was significantly associated with increased RCC risk (Fig. 3)
Summary
This meta-analysis suggests that there may be a relationship between the GSTM1 and GSTT1 wild-type genotype and RCC. Glutathione S-transferases (GSTs) are a superfamily of enzymes that are subdivided into 7 classes (α , μ , ω , π , σ, θ, ξ )[6 ], and are known to protect cells by catalyzing the detoxification of electrophilic compounds, including exogenous products (carcinogens, therapeutic drugs, environmental toxins) and endogenous oxidative products, through conjugation with glutathione[7]. This conjugation reaction is an important step of detoxification and facilitates their excretion from the body, thereby decreasing the associated toxicity.
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