Introduction: Bladder cancer has been linked to several occupations that involve the use of solvents, but only perchloroethylene, used in the dry-cleaning industry, is classified as probably carcinogenic to humans. The role of other commonly used solvents is still unclear. Here, we evaluated exposure to solvents and risk of bladder cancer in 1182 incident cases and 1408 controls from a population-based study. Methods: Exposure to 21 specific solvents was quantitatively assessed using a job-exposure matrix (CANJEM). Because exposure to benzene, toluene and xylene often co-occur, we created two additional sets of metrics of combined benzene, toluene and xylene (BTX) exposure: 1) CANJEM based BTX metrics and 2) Hybrid BTX metrics, which used a novel approach that integrated the CANJEM based BTX metrics together with responses to lifetime occupational histories and exposure-oriented modules to incorporate within-job, subject-specific details about tasks and chemicals into the exposure assessment. Odds ratios (ORs) and 95% confidence intervals (95% CI) were estimated using logistic regression. Results: Bladder cancer risks were significantly increased among those ever exposed to benzene (OR=1.63, 95%CI: 1.14-2.32), toluene (OR=1.60, 95%CI: 1.06-2.43), and xylene (OR=1.67, 95%CI: 1.13-2.48) individually. We observed a statistically significant exposure-response relationship for cumulative BTX exposure, with a stronger association observed with hybrid BTX metrics (ORQ1vsUnexposed=1.26, 95% CI: 0.83-1.90; ORQ2vsUnexposed=1.52, 95% CI: 1.00-2.31; ORQ3vsUnexposed=1.88, 95% CI: 1.24- 2.85; and ORQ4vsUnexposed=2.23, 95% CI: 1.35- 3.69) (p-trend=0.001) than with CANJEM based BTX metrics (p-trend=0.02). Conclusions: In our population-based study, BTX exposure was frequent among automobile mechanics, shoemakers, and painters. The identification of an increased risk for these solvents highlights a little recognized occupational exposure that may play a role in the etiology of bladder cancer. SOURCE OF Funding: This work was supported by the Intramural Research Program of the National Institutes of Health, National Cancer Institute, Division of Cancer Epidemiology and Genetics (ZIA CP010125-27).
