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Project Details

Bladder Cancer Case-Control Study in Córdoba, Argentina

Photo of lab workers
Project Summary: 

Based in Villa María, Córdoba, there are three major components for which final data analysis and report preparation is underway:

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.

Contact Person: 
Jane Liaw
Contact Person's Email Address: 
janeliaw@berkeley.edu
Department/Center: 
Arsenic Health Effects Research Program
Principal Investigators: 
Allan Smith
Research Publications and Reports: 
Website for Project or Program: 
Publication Date: 
2010