Identification of an NAD(P)H

quinone oxidoreductase polymorphism and its association with lung cancer and smoking

Elizabeth A. Rosvold, Katherine A. McGlynn, Edward D. Lustbader, Kenneth Buetow

Research output: Contribution to journalArticle

124 Citations (Scopus)

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 (χ2 = 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 (χ2 = 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.

Original languageEnglish (US)
Pages (from-to)199-206
Number of pages8
JournalPharmacogenetics
Volume5
Issue number4
DOIs
StatePublished - 1995
Externally publishedYes

Fingerprint

NAD
Lung Neoplasms
Oxidoreductases
Smoking
Genotype
Genes
Mutation
Gene Frequency
Population
Exons
Chromosomes
Alleles
Morbidity
Cell Line
DNA
Enzymes
benzoquinone
Neoplasms

Keywords

  • Lung cancer
  • NAD(P)H:quinone oxidoreductase
  • NQO1 gene
  • Polymorphism
  • Smoking

ASJC Scopus subject areas

  • Genetics
  • Pharmacology, Toxicology and Pharmaceutics(all)

Cite this

Identification of an NAD(P)H : quinone oxidoreductase polymorphism and its association with lung cancer and smoking. / Rosvold, Elizabeth A.; McGlynn, Katherine A.; Lustbader, Edward D.; Buetow, Kenneth.

In: Pharmacogenetics, Vol. 5, No. 4, 1995, p. 199-206.

Research output: Contribution to journalArticle

Rosvold, Elizabeth A. ; McGlynn, Katherine A. ; Lustbader, Edward D. ; Buetow, Kenneth. / Identification of an NAD(P)H : quinone oxidoreductase polymorphism and its association with lung cancer and smoking. In: Pharmacogenetics. 1995 ; Vol. 5, No. 4. pp. 199-206.
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