Role of NAD(P)H: quinone oxidoreductase polymorphism at codon 187 in susceptibility to lung, laryngeal and oral/pharyngeal cancers

NAD(P) H: quinone oxidoreductase (NQO1) has been proposed to play a protect ive role against the toxic effects of benzo[a] pyrene quinones. The (CT)-T- 609 base change in the NQO1 gene, resulting in a Pro(187)Ser amino acid cha nge in the protein, has been associated with deficient enzyme activity. We examined whether this polymorphism modified the risks of smoking-related ca ncers in a case-control study involving patients with lung cancer. n = 150) , laryngeal cancer. n = 129), oral/pharyngeal cancer (n = 121) and control individuals. n = 172), all Caucasian smokers. No statistically significant associations were observed between the NQO1 genotypes and smoking-related c ancers, although the Ser/Ser genotype was associated with a tendency toward s increased risk for lung cancer (odds ratio [OR] = 2.2, 95% confidence int erval [CI] 0.7-6.7) and for oral/pharyngeal cancer (OR = 2.3, 95% CI 0.6-8. 2). No significant interaction between the NQO1 genotype and either smoking exposure or GSTM1 genotype was found. Our results are consistent with the hypothesis that lack of NQO1 activity may be involved in some smoking-relat ed cancers. However, they were based on small numbers of individuals with t he putative at-risk genotype, and the associations did not reach statistica l significance. Moreover, these results contrast with those observed in som e other ethnic populations, where a protective effect of the NQO1 Ser allel e was found. Further studies are therefore clearly needed for a better unde rstanding of the potential role of NQO1 activity in tobacco-related cancers .