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

Association of NQO1 polymorphism with spontaneous breast cancer in two independent populations

“…Exchange of the Proline at position 187 by Serine leads to a nonfunctional enzyme (Nebert et al, 2002). Individuals homozygous for the 187S allele have a high risk for aplastic anaemia and leukaemia (Nebert et al, 2002).…”

“…Exchange of the Proline at position 187 by Serine leads to a nonfunctional enzyme (Nebert et al, 2002). Individuals homozygous for the 187S allele have a high risk for aplastic anaemia and leukaemia (Nebert et al, 2002). Reports about the association of the P187S polymorphism with lung cancer are inconsistent (Chen et al, 1999;Lewis et al, 2001).…”

“…BRCA1 and BRCA2 are the well-established susceptibility genes for familial breast cancer (Dunning et al, 1997(Dunning et al, , 2001Healey et al, 2000;Nathanson and Weber, 2001;Goode et al, 2002), TP53 is a gene involved in apoptosis (Dumont et al, 2003), ApoE influences lipid metabolism and cardiovascular disease (Menzel et al, 1983) and may be involved in tumour proliferation (Moysich et al, 2000;Zunarelli et al, 2000), NQO1 is engaged in carcinogen metabolism (Nebert et al, 2002) and GNB3 is part of a signal transduction pathway (Siffert et al, 1998).…”

The NQO1 rs1800566 Polymorphism and Risk of Bladder Cancer: Evidence from 6,169 Subjects

“…A number of single nucleotide polymorphisms (SNPs) have been discovered in this gene (Nebert et al, 2002), of which rs1800566 polymorphism, a C-to-T transition at nucleotide position 609 in exon 6, has been studied by various researchers. Genotype-phenotype studies demonstrated that this kind of polymorphism is associated with a decreased activity of NQO1 enzymatic activity and shows a phenotypic gene-dose effect (Siegel et al, 1999;Basu et al, 2004;Ross et al, 2004).…”

Aspectos toxicológicos do benzeno, biomarcadores de exposição e conflitos de interesses

“…Alternativamente, o benzeno epóxido pode ser convertido a diidrodiol benzeno e, em seguida, a catecol, sendo essas reações de conversão catalisadas pelas enzimas hidrolase e diidrodiol desidrogenase, respectivamente. Outras vias metabólicas incluem as reações do benzeno epóxido com a glutationa, formando o ácido S-fenilmercaptúrico 2,3 ; e com a CYP2E1, formando a oxepina, a qual sofre reação de abertura do anel, catalisada pelo ferro, produzindo o trans,trans-muconaldeído com subsequente metabolização a ácido trans,trans-mucônico 3,4 . A produção de metabólitos de benzeno primários ocorre principalmente no fígado, via metabolização pela enzima CYP2E1, e também nos pulmões, via reações enzimáticas de CYP2E1, CYP2F1 e CYP2A13.…”