GSTP1 Gene Ile105Val Polymorphism Causes an Elevated Risk for Bladder Carcinogenesis in Smokers

Abstract

Background: The glutathione S transferase (GST) family of enzymes plays a vital role in the phase II biotransformation of environmental carcinogens, pollutants, drugs and other xenobiotics. GSTs are polymorphic and polymorphisms in GST genes have been associated with cancer susceptibility and prognosis. GSTP1 is associated with risk of various cancers including bladder cancer. A case control study was conducted to determine the genotype distribution of GSTP1 A>G SNP, to elucidate the possible role of this SNP as a risk factor in urinary bladder cancer (UBC) development and to examine its correlation with clinico-pathologic variables inUBC cases. Materials and Methods: Using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) approach, we tested the genotype distribution of 180 bladder cancer patients in comparison with 210 cancer-free controls from the same geographical region with matched frequency in age and gender. Results: We did not observe significant genotype differences between the control and bladder cancer patients overall with an odds ratio (OR)=1.23 (p>0.05). The rare allele (AG+GG) was found to be present more in cases (28.3%) than in controls (24%), though the association was not significant (p<0.05). However, a significant risk of more than 2-fold was found for the variant allele (AG+GG) with smokers in cases as compared to controls (p>0.05). Conclusions: Thus, it is evident from our study that GSTP1 SNP is not implicated overall in bladder cancer, but that the rare, valine-related allele is connected with higher susceptibility to bladder cancer in smokers and also males.

Effects of Glutathione S-Transferases (GSTM1, GSTT1 and GSTP1) gene variants in combination with smoking or drinking on cancers: A meta-analysis

“…Finally, 85 articles (19,604 cases and 23,710 controls) were kept (Fig. 1), of which 70 articles (16,131 cases and 19,696 controls) were about the relationship between GSTM1 and cancers [4,5,16,17,24–89] (Table 1); 49 articles (11,555 cases and 14,606 controls) were about the relationship between GSTT1 and cancers [4,5,16,24,25,27–31,33,34,36–39,41,42,44–49,51,52,56,58,60,61,63,65–68,70,74–76,79,80,82–85,87,88,90–93] (Table 2); and 31 articles (8518 cases and 9884 controls) were about GSTP1 and cancers [5,16,17,24,30,31,34,36,42,44,45,47,49,52,59,66,67,70,79,88,94–103] (Table 3) among smokers. Among these researches, 8 articles mentioned the classification of smoking levels (20 pack-year).…”

Functional RsaI/PstI Polymorphism in Cytochrome P450 2E1 Contributes to Bladder Cancer Susceptibility: Evidence from a Meta-analysis

“…Cytochrome P450 (CYP) is the most important phase I enzymes system, which is usually involved in the activation of carcinogens; and phase II enzymes, particularly N-acetyltransferase (NAT) and glutathione s-transferase (GSTs), which mostly detoxify the products to be excreted in the urine and possibly played an important role in cancer etiology (Steck and Hebert, 2009;Zgheib et al, 2010). Although studies suggested that CYP2E1 genetic polymorphisms have an impact on the incidence of cancer (Danko and Chaschin, 2005), epidemiological studies suggest that the NAT1, NAT2, GSTM1 and GSTP1 polymorphisms modify the risk of developing cancers of the urinary bladder Pandith et al, 2013;Zabost et al, 2013). Therefore, not only is CYP2E1 suspected to be involved with the development of bladder cancer, but also other DMEs genetic factors may be associated with bladder cancer.…”

Genetic Polymorphisms Involved in Bladder Cancer: A Global Review

“…Since these molecules contribute to the metabolism of potential carcinogens, any polymorphism affecting their expression or function may lead to cancer [31]. Most articles show that in most populations, the GSTM1 null genotype [32][33][34][35][36][37][38][39][40][41][42][43][44][45][46][47] and rs1695 in GSTP1 [16,19,33,40,42,[48][49][50][51][52][53][54][55] increase the risk for BC. However, a Chinese study showed that the GSTT1 null genotype was associated with a decreased risk for BC [36].…”