Occupational and Environmental Exposures, Genetic Polymorphisms and Bladder Cancer Risk among Male Farmers in Egypt

Abstract

Objectives: To examine associations between bladder cancer risk and (1) farming as an occupation, (2) pesticide exposure, and (3) polymorphisms of the GSTM1, GSTT1, NQO1, and SOD2 genotypes among men farmers in Egypt, as well as (4) indirect exposure to farming among women living with a farmer. Methods: We used questionnaire and genotype data from a multicenter case-control study in Egypt. Cases confirmed to have either urothelial carcinoma (UC) or squamous cell carcinoma (SCC), and frequency-matched population controls were included. Unconditional logistic and polytomous (where appropriate) regression models were used to estimate the odds ratios (OR) and 95% confidence intervals (CIs). Results: Among the 1525 male cases confirmed as primary urinary bladder carcinomas and 2069 controls, we found that working as a farmer was significantly associated with increased bladder cancer risk for both smokers and non-smokers (AOR=1.72; 95% CI: 1.43-2.05, and AOR=3.46; 95% CI: 2.56-4.66, respectively) after adjustment for other known risk factors. To a lesser extent women living with farmers had increased odds of having bladder cancer (adjusted OR=1.33; 95% CI: 0.98-1.79). Among the men farmers (cases=885 and controls=840), pesticide exposure was associated with increased risk of UC type of cancer (OR=1.28; 95% CI: 1.01-1.61) and the odds of having UC increased as the duration and frequency of exposure to pesticides increased. Furthermore, the highest risk was found among exposed farmers with genes encoding for moderate to low activity of the enzymes NQO1 and SOD2. There were no associations between the GSTT1 and GSTM1 null genotypes and bladder cancer risks among Egyptian farmers. Conclusions: Our findings suggest that working as or living with a farmer is associated with increased bladder cancer risk in Egypt. Exposure to pesticides and polymorphisms of the NQO1 and SOD2 genotypes appear to be among the contributing risk factors.