Solvent Exposure, Genetic Susceptibility, and Risk of Bladder Cancer

Area of Science:

• Environmental Health
• Genetics
• Oncology

Background:

• Occupational exposure to mononuclear aromatic organic solvents, including benzene, toluene, and xylene (BTX), is linked to increased bladder cancer risk.
• The precise mechanisms underlying BTX's influence on bladder cancer remain unclear.

Purpose of the Study:

• To investigate the interaction between BTX solvent exposure and genetic susceptibility markers in bladder cancer.
• To identify genetic variants that modify the risk associated with occupational BTX exposure.

Main Methods:

• A population-based case-control study involving 1,182 bladder cancer cases and 1,408 controls.
• Assessment of lifetime occupational exposure to benzene, toluene, xylene, and BTX using occupational histories and a job-exposure matrix.
• Genotyping of genetic variants in bladder cancer susceptibility loci and solvent metabolism pathways from buccal cell samples.

Main Results:

• Individuals with high cumulative benzene exposure and a risk allele in CASC15 (rs72826305) showed a significantly increased bladder cancer risk (OR = 2.56).
• Suggestive joint effects were observed between benzene exposure and genetic risk variants in FGFR3 and GSTT1.
• Bladder cancer risk was elevated in individuals exposed to BTX solvents who also carried common genetic variants in CASC15, FGFR3, and GSTT1.

Conclusions:

• Bladder cancer risk is amplified by the combined effect of occupational BTX solvent exposure and specific genetic polymorphisms.
• The interplay between genetic predisposition and environmental exposures is crucial in the etiology of bladder cancer.
• Findings support the role of joint contributions of genetics and occupational exposures in bladder cancer development and inform prevention strategies.