Bladder cancer case-control study in Córdoba, Argentina


This study was based in Villa María, Córdoba. The study is defined by 3 major components:


1) Arsenic and bladder cancer dose-response: Bladder cancer cases and age- and sex-matched population controls from the County of Unión have been interviewed in detail including lifelong residential histories, sources of drinking water and smoking histories. Water samples have been collected from both the current residences and where possible, from previous residences. Historical data on arsenic measurements in public water supplies have also been collected. We are currently analyzing these data to assess the relationship between arsenic exposure and bladder cancer risk.  This will include an examination of the possible synergistic effect of cigarette smoking. 

2) Metabolism: First-morning urine samples were collected from cases and controls. Analyses for inorganic arsenic and its methylated metabolites were conducted in the laboratory of Professor David Kalman, University of Washington. Cases and controls are being compared to see if they differ in arsenic methylation patterns. 

3) Molecular epidemiology: Tumor DNA has been analyzed for genetic alterations using a three-tiered approach: 

o screening of the entire genome for gains and losses using comparative genomic hybridization (CGH);

o specific analyses of chromosomes 9 and 17p for loss of heterozygosity using PCR- based methods; 

o analysis of the p53 gene for mutations, using polymerase chain reaction-single-strand conformation (PCR-SSCP). 

The frequency and pattern of these genetic alterations in bladder tumors of arsenic-exposed and unexposed cases is being compared. The potential synergistic action of arsenic on genotoxic effects of cigarette smoking is currently being assessed. In addition, susceptibility differences between cases and controls is being investigated by identifying the presence or absence of the glutathione S-transferases GSTM1 and GSTT1 null genotypes in buccal cells and by comparing urinary arsenic methylation patterns. 


Argentina mortality study

Mortality from internal cancers was identified in areas of the Province of Córdoba, Argentina, which in the past had high levels of arsenic in drinking water. The results concerning bladder cancer have been published. The analyses concerning mortality from other cancers has also been published. Increased risks for kidney and lung cancers were found in the exposed areas.




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