The CYP2D6 extensive metabolizer genotype is associated with increased risk for bladder cancer.

Inheritance of certain polymorphic metabolizing genes is associated with the development of a number of environmental cancers and may also influence the clinicopathological tumor outcome. We have investigated the association between the inheritance of the polymorphic cytochrome P-450 2D6 (CYP2D6) gene and the development of transitional and squamous cell carcinomas (TCC and SCC) of the bladder in 37 Egyptian cancer patients and 27 matched controls. Genotypic analysis using the polymerase chain reaction (PCR) and the restriction fragment length polymorphism (RFLP) assays revealed that the CYP2D6 extensive metabolizer genotype (CYP2D6*1A) is over represented in bladder cancer patients compared to controls (79 versus 44%, respectively) and is significantly associated with increased risk for bladder cancer (odds ratio (OR) = 4.5, 95% confidence limit (CL) = 1.3-15.7, P = 0.006). Our results also indicate that individuals who have inherited this genotype are more likely to develop TCC (OR = 5.9, 95% CL = 1.4-27.9, P = 0.006) rather than SCC (OR = 3.1, 95% CL = 0.7-15.9; P = 0.09). When the relative risk associated with this genotype was estimated among subjects who were smokers or schistosoma infected, the same tendency towards the development of TCC was observed. These data suggest that the predisposing CYP2D6 gene may not only increase the risk for bladder cancer among Egyptians, but may also influence the clinicopathological tumor outcome.

GSTM1 and GSTT1 genes are potential risk modifiers for bladder cancer.

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.

The correlation between serum total cholesterol and some trace elements in serum, liver and heart of rats fed high cholesterol diet.

The work indicates the link between the serum cholesterol, atherosclerosis and certain metal metabolism. 122 adult albino rats were used in this study and classified into 5 groups: Control group, 29 rats fed the stock diet; group I, 32 rats fed the stock diet with 1% cholesterol for 6 weeks; group II, 36 rats fed the stock diet with 1% cholesterol for 8 weeks; group IIIA, 17 rats fed the stock diet and 0.2 ml oil/day orally for 8 weeks and group IIIB, 18 rats fed the stock diet and 0.2 ml oil with cholesterol daily (50 mg cholesterol/1 ml oil) for 8 weeks. The results obtained showed that: 1. A positive correlation was found between serum total cholesterol and serum copper, cadmium and Cd/Zn ratio, whereas a negative correlation occurred between serum total cholesterol and serum Zinc and Zn/Cu ratio. 2. A positive correlation was found between serum total cholesterol and cadmium, Zn/Cu and Cd/Zn ratio in liver. On the other hand, a negative correlation occurred between serum total cholesterol and copper in liver. 3. A positive correlation was found between serum total cholesterol and Zn/Cu ratio in heart which was negative in heart copper, cadmium and Cd/Zn ratio. Histopathological examination of liver sections of animals treated with cholesterol revealed the presence of mild degree of fatty change, while the kidney tissues showed glomerular lesion in the form of obliteration of Bowman's capsule with increased cellularity inside, beside degenerated tubules and interstitial fibrosis.