Influence of polymorphisms on biomarkers of low benzene exposure

Benzene is a human carcinogen and an ubiquitous environmental pollutant. This investigation evaluated the influence of genetic polymorphisms of metabolic enzymes CYP2E1 (RsaI and DraI), GSTM1, GSTT1 and NQO1 on some biomarkers of benzene exposure, namely: urinary t,t-muconic acid (t,t-MA), S-phenylmercapturic acid (S-PMA) and benzene (U-benzene). Italian petrochemical workers, side-products workers of a coke oven plant, gas station attendants, urban policemen, bus drivers and 6 groups of controls were studied (632 subjects). Median personal benzene exposure ranged between 99 and 2 μg/m3. U-benzene, but not t,t- MA and S-PMA, showed an exposure-related increase. All the biomarkers were strongly increased by cigarette smoking. Significant correlations of the biomarkers with each other and with urinary cotinine were found. In a preliminary analysis performed on a subset of 415 subjects, an effect of the presence of a variant CYP2E1 (RsaI and/or DraI) allele on t,t-MA (increase) and U-benzene (decrease) was found. Using multiple linear regression models we simultaneously evaluated the contribution of genetic polymorphism, smoking habit and job on the level of the investigated biomarkers. R2 was up to 0.55 for U-benzene. For pre-shift t,t-MA, both the presence of a variant allele of CYP2E1 (RsaI) and of smoking habit were found to double the levels, while no significant influence was exerted by job. For U-benzene (both pre- and post–shift), the presence of a variant allele of CYP2E1 (RsaI) decreased the level of one third, smoking habit increased the level 3-4 times while being a traffic policeman or a gasoline attendant in comparison with being a control increased the level 1.5-2.0 and 2.8-3.3 times, respectively. The result of our study suggests, for the first time, a role of the genetic polymorphisms of CYP2E1 in the metabolism of benzene.