NAD(P)H:quinone oxidoreductase (NQO1) polymorphism, exposure to benzene, and predisposition to disease: A HuGE review

Daniel W. Nebert, Amy L. Roe, Susan E. Vandale, Eula Bingham, Gregory G. Oakley

Research output: Contribution to journalReview article

151 Scopus citations

Abstract

NAD(P)H:quinone oxidoreductase (NQO1) catalyzes the two- or four-electron reduction of numerous endogenous and environmental quinones (e.g., the vitamin E a-tocopherol quinone, menadione, benzene quinones). In laboratory animals treated with various environmental chemicals, inhibition of NQO1 metabolism has long been known to increase the risk of toxicity or cancer. Currently, there are 22 reported single-nucleotide polymorphisms (SNPs) in the NQO1 gene. Compared with the human consensus (reference, "wild-type") NQO1*1 allele coding for normal NQO1 enzyme and activity, the NQO1*2 allele encodes a nonsynonymous mutation (P187S) that has negligible NQO1 activity. The NQO1*2 allelic frequency ranges between 0.22 (Caucasian) and 0.45 (Asian) in various ethnic populations. A large epidemiologic investigation of a benzene-exposed population has shown that NQO1*2 homozygotes exhibit as much as a 7-fold greater risk of bone marrow toxicity, leading to diseases such as aplastic anemia and leukemia. The extent of the contribution of polymorphisms in other genes involved in the metabolism of benzene and related compounds-such as the P450 2E1 (CYP2E1), myeloperoxidase (MPO), glutathione-S-transferase (GSTM1, GSTT1), microsomal epoxide hydrolase (EPHX1), and other genes-should also be considered. However, it now seems clear that a lowered or absent NQO1 activity can increase one's risk of bone marrow toxicity, after environmental exposure to benzene and benzene-like compounds. In cancer patients, the NQO1*2 allele appears to be associated with increased risk of chemotherapy-related myeloid leukemia. Many other epidemiological studies, attempting to find an association between the NQO1 polymorphism and one or another human disease, have now begun to appear in the medical literature.

Original languageEnglish (US)
Pages (from-to)62-70
Number of pages9
JournalGenetics in Medicine
Volume4
Issue number2
DOIs
StatePublished - Mar 2002

Keywords

  • Benzene exposure
  • Benzene metabolism
  • CYP2E1
  • Myelodysplastic syndrome
  • NAD(P)H:Quinone oxidoreductase (NQO1) gene polymorphism
  • Therapy-related acute myeloid leukemia

ASJC Scopus subject areas

  • Genetics(clinical)

Fingerprint Dive into the research topics of 'NAD(P)H:quinone oxidoreductase (NQO1) polymorphism, exposure to benzene, and predisposition to disease: A HuGE review'. Together they form a unique fingerprint.

Cite this