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Rosvold EA , McGlynn KA , Lustbader ED , Buetow KH
Identification of an Nad(P)H-Quinone Oxidoreductase Polymorphism and Its Association with Lung-Cancer and Smoking
Pharmacogenetics. 1995 Aug;5(4) :199-206
PMID: ISI:A1995RQ64900003   
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Abstract
The enzyme NAD(P)H:quinone oxidoreductase (NQO1) catalyses bioreduction and bioactivation reactions. A mutation in the NQO1 gene had previously been demonstrated in a cancer cell line with reduced NQO1 activity. In this study, several regions of the NQO1 locus were examined for constitutional variation at the DNA level. The previously described mutation in exon 6 was detected by the single-strand conformation polymorphism technique. This was confirmed by sequencing to result from a C- ->T substitution. Genotype analysis in the Centre d'Etude Polymorphisme Humain (CEPH) reference]panel revealed two alleles with frequencies of 0.87 and 0.13 and demonstrated Mendelian transmission Genotype distributions were consistent with Hardy-Weinberg equilibrium. Linkage analysis mapped the gene locus to chromosome 16q. NQO1 was felt to be a candidate gene for the susceptibility to lung cancer, given its potential role in protection against carcinogenic compounds. The frequency of NQO1 variants was examined in 150 lung cancer cases and in two reference populations. The allele distribution in CEPH parent controls was significantly different from cases (chi(2) = 5.52, p = 0.019), but no difference was noted between cases and a healthy local reference population. When the local reference distribution was stratified on smoking status, a significant difference was observed (chi(2) = 3.88, p = 0.048). The distribution in smokers was more similar to the lung cancer cases, and the non-smokers more similar to the distribution in CEPH parents who are predominantly non-smokers. These results provide preliminary evidence for a possible relation between NQO1 variation and smoking-related morbidity or behaviour.
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Times Cited: 68 Article RQ649 PHARMACOGENETICS