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Carcinogenesis Advance Access published online on October 21, 2004
Carcinogenesis, doi:10.1093/carcin/bgh314
© 2004 by Oxford University Press
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Received June 8, 2004
Revised September 23, 2004
Accepted October 10, 2004

MOLECULAR EPIDEMIOLOGY AND CANCER PREVENTION

NQO1 T allele associated with decreased risk of later age at diagnosis lung cancer among never smokers: results from a population-based study

C. H. Bock 1*, A. S. Wenzlaff 1, M. L. Cote 1, S. J. Land 2, and A. G. Schwartz 1

1 Population Studies and Prevention Program, Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, MI
2 Population Studies and Prevention Program, Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, MI; Center for Molecular Medicine and Genetics, Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, MI; Molecular Biology and Human Genetics Program, Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, MI

* To whom correspondence should be addressed.
C. H. Bock, E-mail: bockc{at}med.wayne.edu


  Abstract

The NAD(P)H:quinone oxidoreductase 1 gene, NQO1, contains a C to T transition at amino acid codon 187 which results in very low enzymatic activity. Previous studies of the association between NQO1 genotype and lung cancer have had mixed findings. This population-based case control study examines the association between NQO1 genotype and lung cancer in the largest sample of never smokers (<100 cigarettes, lifetime) to date. Cases (n=161) were identified through the metropolitan Detroit Surveillance, Epidemiology and End Results (SEER) program, and five-year age- and race-matched population-based controls (n=173) were identified using random digit dialing. Allele frequencies of C and T, respectively, were 0.79 and 0.21 in Caucasians, and 0.84 and 0.16 in African Americans. Among those diagnosed ≥ age 50 years, C/T and T/T genotyped individuals had 0.48 times lower lung cancer risk than individuals with C/C genotype (95% CI: 0.27-0.87). There was a non-significant suggestion of a protective effect associated with the T allele among those with a history of environmental tobacco smoke exposure (OR=0.57, 95% CI: 0.32-1.03) but not among those without (OR=0.98, 95% CI: 0.41-2.38). Sex, race, family history of lung cancer, and histologic type did not modify the effect of NQO1 genotype on lung cancer risk. The observed risk reductions may be attributable to the greatly reduced procarcinogen activating of NAD(P)H:quinone oxidoreductase 1 in individuals with at least one copy of the T allele.


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