Genetic polymorphism of drug metabolizing enzymes (CYP2E1, GSTP1) and susceptibility to bladder cancer in North India.

Glutathione-S-transferases (GSTs) are active in the detoxification of wide variety of endogenous or exogenous carcinogens and genetic polymorphisms of CYP2E1 and GSTP1 genes have been studied extensively to evaluate the relative risk of various cancers. In the present study, we examined associations with CYP2E1 and GSTP1 gene polymorphisms in sporadic bladder cancers from North Indian patients. The subjects were 106 bladder cancer (Ca-B) cases and 162 age-matched controls. The GSTP1 313 A/G polymorphism was determined by the PCR/RFLP method using peripheral blood DNA. Binary Logistic Regression Model was used for assessing differences in genotype prevalence and their associations between patient and the control group. We observed a non-significant association in Pst1 polymorphism of the CYP2E1 gene; though the A/G genotype (OR = 2.69, 95% CI=1.57- 4.59, P= 0.000) and G/G genotype (OR = 7.68, 95% CI=2.77- 21.26, P= 0.000) of the GSTP1 gene polymorphism alone or in combination with tobacco users were highly significant (OR=24.06; 95% CI: 4.80- 120.42; P =0.000) when compared to the controls. The results of our study demonstrated that the GSTP1 313 G/G polymorphism is a strong predisposing risk factor for bladder cancer in the North Indian population.

Stone composition, metabolic profile and the presence of the gut-inhabiting bacterium oxalobacter formigenes as risk factors for renal stone formation

To examine stone composition, metabolic evaluation and colonization of Oxalobacter formigenes as risk factors for renal stone formation. Subjects and Eighty patients with renal stones and 70 healthy controls were enrolled in the study. Of the 80 patients, 48 were first-time stone formers [FSF] and 32 were 'recurrent' stone formers [RSF], recurrent indicating 2 or more episodes of stone formation. Stone analysis by X-ray crystallography, 24-hour urine metabolic profile and detection of O. formigenes-specific DNA by PCR were performed for each patient. Detection of O. formigenes was also performed on 45 and urinary metabolic profile on an additional 25 controls. Calcium oxalate monohydrate was the major component of stones, hyperoxaluria and hypocitraturia were the most common urinary abnormalities in the 80 patients, 46% of RSF patients had hypercalciuria. Urinary abnormalities were far less frequent in the controls, with the exception of hypocitraturia [40%]. Of the urinary metabolites, only calcium levels were significantly different [p < 0.05] between FSF [6.50 +/- 4.08 mmol/24 h] and RSF [8.21 +/- 5.26 mmol/24 h] patients. Colonization of O. formigenes was higher in controls [62.2%] than in FSF [33.3%] or RSF [28%] patients, it was least in patients with more than 4 episodes [7%] of stone formation. The findings indicate that lack of colonization of O. formigenes may be an important risk factor for recurrence of stone formation [calcium oxalate monohydrate]