OBJECTIVES: This study was performed to investigate the effect of genetic polymorphisms on the oxidative genetic damage caused by benzene exposure in workers. METHODS: We measured urinary t,t-muconic acid levels as a biomarker for benzene exposure and measured the level of urinary 8-OHdG to assess oxidative DNA damage in benzene-exposed healthy male workers. Genetic polymorphisms of ALDH2 and CYP2E1 were determined by TaqMan assay. We estimated Pearson correlation coefficients between urinary t,t-muconic acid and 8-OHdG according to the genetic polymorphisms of CYP2E1 and ALDH2. RESULTS: There was a significant relationship between urinary t,t-muconic acid and 8-OHdG concentrations in overall subjects (R=0.532, p<0.001). Smokers showed a higher correlation coefficient between the markers than nonsmokers did (R=0.520 vs. 0.010). Individuals with CYP2E1 c1/c1 genotype also showed a higher correlation coefficient between them than those with CYP2E1 c1/c2 or c2/c2 genotypes (R=0.670 vs. -0.145). In multiple linear regression analysis including smoking status, sorbic acid intake, age and genetic polymorphisms of CYP2E1 and ALDH2 as the independent variables, urinary t,t-muconic acid showed a significant association with urinary 8-OHdG. CONCLUSIONS: There was a significant correlation between urinary 8-OHdG and urinary t,t-muconic acid in benzene-exposed workers. This relationship was affected by genetic polymorphisms of CYP2E1and ALDH2.