The influence of cytochrome P450 1A1 and glutathione S-transferase M1 genotypes on biomarker levels in coke-oven workers

The present study has the aim of evaluating gene-environment interaction on the levels of different biomarkers in coke-oven workers exposed to PAH. In order to assess whether the levels of some biomarkers (PAH-DNA adducts, ni tro-PAH adducts to Hb and MN frequency) could be modulated by the genetic m etabolic polymorphisms for CYP1A1 and GSTM1, we analysed in 76 coke-oven wo rkers and 18 controls the CYP1A1 (MspI and Ile/Val sites) and the GSTM1 gen otypes by a PCR assay, In individuals with shared setup of CYP1A1 or GSTM1 genotypes, we analysed how the specified biomarkers correlated with total P AH exposure (urinary levels of l-hydroxypyrene) both by a stratified analys is and logistic regression modelling. Statistically significant (P = 0.03 a nd P = 0.01) higher percentages of the more susceptible GSTM1- subjects com pared to the GSTM1+ subjects and of the more susceptible CYP1A1 Ile/Val ind ividuals compared to the CYP1A1 Ile/Ile individuals were detected for high levels of PAH-DNA adducts in the high exposure group (namely high levels of 1-OHP). A statistically significant association was observed between incre ased PAH-DNA adduct levels and the more susceptible GSTM1- genotype (P.O.R. = 4.18, P = 0.03) in a logistic regression modelling and a significant int eraction between PAH exposure and GSTM1-genotype was found for PAH-DNA addu cts. No effect of these metabolic genotypes was observed for MN frequency a nd nitro-PAH adducts to Hb. In conclusion, a gene-environment interaction b etween PAH exposure and two metabolic genotypes involved in activation (CYP 1A1) and detoxification (GSTM1) of PAHs, respectively, has been identified.