Metabolic
enzymes involved in
benzene activation or detoxification, including
NAD(P)H,
quinone oxidoreductase 1 (NQO1),
cytochrome P450 2E1 (
CYP2E1),
myeloperoxidase (MPO),
glutathione-S-transferase mu-1 (GSTM1), and
glutathione-S-transferase theta-1 (GSTT1), were studied for their roles in human susceptibility to
benzene poisoning. The potential interactions of these metabolic
enzymes with lifestyle factors such as cigarette smoking and alcohol consumption were also explored. We studied 156
benzene-
poisoning patients and 152 workers occupationally exposed to
benzene in South China. Sequencing, denaturing HPLC, restriction fragment-length polymorphism, and polymerase chain reaction were used to detect polymorphisms on the promoters and complete coding regions of NQO1,
CYP2E1, MPO, and the null genotypes of GSTM1 and GSTT1. Seventeen single nucleotide polymorphisms (SNPs) were identified in NQO1,
CYP2E1, and MPO genes, including 6 novel SNPs in
CYP2E1 and MPO. Of the subjects who smoked and drank alcohol, an 8.15-fold [95% confidence interval (CI), 1.43-46.50] and a 21.50-fold (95% CI, 2.79-165.79) increased risk of
benzene poisoning, respectively, were observed among the subjects with two copies of NQO1 with a C-to-T substitution in
cDNA at
nucleotide 609 (
c.609 C>T variation; i.e., NQO1
c.609 T/T) compared to those with the heterozygous or wild (NQO1
c.609 C/T and
c.609 C/C) genotypes. Our data also indicated that individuals with
CYP2E1 c.-1293 C/C and c.-1293 G/C, and NQO1
c.609 T/T, and GSTT1 null genotypes tended to be more susceptible to
benzene toxicity. Our results suggest that the combined effect of polymorphisms in NQO1,
CYP2E1, and GSTT1 genes and lifestyle factors might contribute to
benzene poisoning.