Polymorphic changes in the GSTM1, CYP2E1 and the CYP2D6 genes have been reported to be individually associated with increased susceptibility to certain cancers. In the present study, the relationship between genetic polymorphism for these genes and development of urinary bladder cancer among Egyptian patients was investigated. Our results indicate that the frequency of bladder cancer patients with the GSTM1 null genotype is significantly higher than that of the normal controls (86.3 and 47.6%, respectively) with an odds ratio (OR) of 6.97 (95% CL -1.59-30.57, Fisher's exact P = 0.008). In contrast, our investigation failed to demonstrate any difference in the distribution of CYP2E1 polymorphism between bladder cancer patients and controls as detected by PstI restriction fragment length polymorphism (RFLP) analysis. RFLP analysis of the CYP2D6 gene revealed a non-significant increase in the number of extensive metabolizers (EM) among the patients compared to the controls (68 versus 48%). However, the EM genotypes enhances the risk further for individuals harboring the GSTM1 null genotype as individuals harboring both the EM and the GSTM1 null genotypes have an odds ratio of 14.0 (95% CL = 1.3- 151.4, Fisher's exact P = 0.02) compared to individuals harboring the EM and the GSTM1 +/+ genotypes. In conclusion, our results indicate that genetic polymorphism, especially in GSTM1 and CYP2D6 could play an important role as host risk factors for development of urinary bladder cancer among Egyptians.
The role of the polymorphic glutathione S-transferase genes GSTM1 and GSTT1 in the development and in the clinicopathological outcome of bladder cancer was investigated in 37 Egyptian bladder cancer patients and 34 matched controls. Of the 37 patients studied, 26 had transitional cell carcinoma (TCC) and 11 had squamous cell carcinoma (SCC). Fourteen out of twenty-six TCC and four out of eleven SCC patients were infected with schistosoma. We observed an increased relative risk for bladder cancer associated with the GSTM1 null genotype (OR = 2.99; 95% CL = 1.01-9.00; p = 0.02). The relative risk was more pronounced in squamous cell carcinoma (SCC) (OR = 5.70; 95% CL = 0.91-36.70; p = 0.03) than in transitional cell carcinoma (TCC) (OR = 2.39; 95% CL = 0.73-7.90; p = 0.08). Our results also indicate that the GSTT1 polymorphism is individually associated with increased risk for bladder cancer (OR = 4.93; 95% CL = 1.39-18.42; p = 0.004) with no preferential increase in risk with respect to the type of the carcinoma. Individuals with the null genotype for both GSTM1 and GSTT1 were at a significantly higher risk for developing bladder cancer than individuals with both genes present (OR = 9.92; 95% CL = 1.84-46.90; p = 0.001). These individuals were more susceptible to developing SCC than TCC (OR = 14.16; 95% CL = 1.35-131.35; p = 0.01; and OR = 8.5; 95% CL = 1.38-60.10; p = 0.007, respectively). In conclusion, our results indicate that the null genotypes for GSTM1 and GSTT1, either individually or in combination, are important host risk factors for bladder cancer. In addition, the null GSTM1 genotype may also affect the clinicopathological tumor outcome. Since the deleted genotypes for GSTM1 and GSTT1 are prevalent in the general population, the identification of these individuals may provide a useful public health approach for early detection and prevention of environmental cancers.
Background and Purpose— Wall shear stress (WSS) has been implicated as an important stimulus for vascular remodeling. The purpose of this study is to measure WSS in AVM arterial feeders using quantitative magnetic resonance angiography pre- and post-embolization/surgery. Methods— Records of patients who underwent AVM embolization and surgical resection at our institution between 2007 and 2013 and had WSS, flow rate, and vessel diameter obtained pre- and post-treatment using quantitative magnetic resonance angiography were retrospectively reviewed. WSS was compared between the feeder and contralateral artery pre- and post-embolization/surgery. Results— Twenty-one patients were included (mean age 34 years, 19% hemorrhagic presentation), with Spetzler–Martin grades 1 to 4. WSS, blood flow, and vessel diameter were assessed in a total of 51 feeder arteries. At baseline, mean WSS was significantly higher compared with the contralateral vessel (29.7±12.0 dynes/cm 2 versus 23.3±11.0 dynes/cm 2 ; P =0.007). After embolization (23.0 dynes/cm 2 versus 22.5 dynes/cm 2 ; P =0.78) and surgery (17.9 dynes/cm 2 versus 23.2 dynes/cm 2 ; P =0.09), WSS was not significantly different than in the contralateral vessel. Reduced WSS post-embolization corresponded to significantly decreased flow (338.1 mL/min versus 170.3 mL/min; P <0.001) and smaller vessel diameter (3.7 mm versus 3.5 mm; P =0.01). Conclusions— Enlargement of cerebral AVM arterial feeders is insufficient to compensate for increased blood flow, creating high WSS. After treatment, flow diminishes and so WSS and vessel diameter concomitantly decrease. Thus, WSS plays a pivotal role in vascular remodeling that may be exploited to monitor AVM response to treatment or understand other high-flow vascular pathologies.
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