EPICURO study-Spanish Bladder Cancer Case-control Study

Duration

1997-

Coordinator

Manolis Kogevinas

Funded by

Ministerio de Ciencia y Tecnología
Fondo de Investigación Sanitaria
European Comission
National Cancer Insitute, Bethesda, MD, USA

The Spanish Bladder Cancer Study (EPICURO study) was initiated in 1997 as a collaborative project of IMIM and the DCEG of the US NCI.

AIMS



To evaluate the risk of bladder cancer in relation to environmental and occupational exposures, including drinking water disinfection-by products, diesel exhaust, solvents, PAHs, based on state-of-the-art exposure assessment.

To evaluate the role of lifestyle factors including tobacco, analgesics/NSAIDS, diet, urination habits, urinary pH in the aetiology of bladder cancer.

To evaluate the effects of genetic susceptibility markers on the risk of bladder cancer and their interaction with environmental exposures



The study is also evaluating clinical, molecular and genetic factors associated with bladder cancer survival (coordinated by N Malats and Paco Real currently at CNIO).

Methods

Hospital-based case-control study conducted in 17 hospitals from 5 areas in Spain including around 1200 cases and 1200 controls. Cases were patients newly diagnosed with histologically confirmed carcinoma of the urinary bladder in 1998-2001, aged 21-80 years. Information on potential risk factors was collected using computer-assisted personal interviews during the hospital admission. About 85% of subjects participated in the study and of those, around 95% provided blood samples.

Main findings

 



Bladder cancer risk is associated with long-term exposure to trihalomethanes (THMs –the most prevalent disinfection by-products) in chlorinated water at levels regularly occurring in industrialized countries. Risk was associated with exposure through ingestion, inhalation and dermal absorption.

Smokers of black tobacco had a 40% higher risk than smokers of blond tobacco no trend in risk with cessation of smoking black tobacco was apparent

Bulky DNA adducts (a biomarker for exposure to PAHs), were not associated with bladder cancer risk among non-smokers with stable environmental and lifestyle factors.

Regular use of nonaspirin NSAIDs was associated with a reduced risk of bladder cancer, which was not modified by polymorphisms in the NSAID-metabolizing gene CYP2C9.

No association was found between hair dye use and bladder cancer. Hair dye use was associated with micronuclei in urothelial cells.

Increased night time voiding frequency was protective and smoking-related risk was reduced by nocturia.

Acidic urine was associated with an increased risk and modified smoking related risk.

Several genetic polymorphisms involved in the metabolism of bladder carcinogens and also in DNA repair were associated with bladder cancer risk.



The study has produced more than 30 publications. Ongoing analyses include the evaluation of occupational exposures, the evaluation of infections, survival analysis and tumour markers and mostly the completion of a GWAS by the US NCI in which the SBCS has been one of the core studies.

Organisation



The study is coordinated by a Steering committee by M Kogevinas PI (IMIM/CREAL), N Malats (co-PI, IMIM/CNIO), P Real (co-PI, IMIM/CNIO), D Silverman PI (NCI), N Rothman (co-PI, NCI), M Garcia-Closas (co-PI, NCI). Mustafa Dosemeci (NCI) was the first PI from NCI’s side before his retirement.

Bladder Cancer Consortium



The SBCS participates in the Bladder cancer consortium in which CREAL participates in the Steering Committee. A first joint paper has been published (Stern et al), and more joint analyses are planned including effects of hairdyes, NSAIDS and various genetic polymorphisms.