TY - JOUR
T1 - An association between a NQO1 genetic polymorphism and risk of lung cancer
AU - Saldivar, Salvador J.
AU - Wang, Yunfei
AU - Zhao, Hua
AU - Shao, Lina
AU - Lin, Jie
AU - Spitz, Margaret R.
AU - Wu, Xifeng
N1 - Funding Information:
This research was supported by National Cancer Institute grants CA55769 and CA86390.
PY - 2005/4/4
Y1 - 2005/4/4
N2 - NAD(P)H:quinone oxidoreductase (NQO1) is a detoxification enzyme that protects against the regeneration of reactive oxygen species chemically induced by oxidative stress, cytotoxicity, mutagenicity, and carcinogenicity. The protection conferred by NQO1 protein reduces certain environmental carcinogens, such as nitroaromatic compounds, heterocyclic amines, and possible cigarette smoke condensate. The gene coding for NQO1 has a genetic polymorphism (C → T) at nucleotide position 609 (i.e. amino acid codon 187) of the NQO1 cDNA. This polymorphism was shown to reduce NQO1 enzyme activity, thereby diminishing the protection provided by NQO1. Therefore, we hypothesized that individuals with the variant NQO1 genotype are at higher risk for lung cancer. Using a case-control study, we genotyped the NQO1 variants successfully by PCR-RFLP in 826 lung cancer patients and 826 healthy control subjects matched for age, sex, ethnicity, and smoking status. The frequency of the NQO1 T-allele was statistically significantly different among three ethnic groups (p < 0.001). In further analysis of Caucasians, the variant NQO1 genotypes (CT and TT) were associated with a marginally increased lung cancer risk (OR = 1.19; 95% CI: 0.95-1.50). The elevated lung cancer risk was only evident in younger individuals (age <62 years old) (OR = 1.46; 95% CI: 1.04-2.05), women (OR = 1.89; 95% CI: 1.33-2.68), and never smokers (OR = 1.80; 95% CI: 1.03-3.13). Furthermore, we found a statistically significant trend in the development of lung cancer at an early age in women with increasing copies of the variant allele (p = 0.03). These results suggest that the NQO1 variant genotype may modulate lung cancer risk, especially in younger individuals (age < 62), women, and never smokers.
AB - NAD(P)H:quinone oxidoreductase (NQO1) is a detoxification enzyme that protects against the regeneration of reactive oxygen species chemically induced by oxidative stress, cytotoxicity, mutagenicity, and carcinogenicity. The protection conferred by NQO1 protein reduces certain environmental carcinogens, such as nitroaromatic compounds, heterocyclic amines, and possible cigarette smoke condensate. The gene coding for NQO1 has a genetic polymorphism (C → T) at nucleotide position 609 (i.e. amino acid codon 187) of the NQO1 cDNA. This polymorphism was shown to reduce NQO1 enzyme activity, thereby diminishing the protection provided by NQO1. Therefore, we hypothesized that individuals with the variant NQO1 genotype are at higher risk for lung cancer. Using a case-control study, we genotyped the NQO1 variants successfully by PCR-RFLP in 826 lung cancer patients and 826 healthy control subjects matched for age, sex, ethnicity, and smoking status. The frequency of the NQO1 T-allele was statistically significantly different among three ethnic groups (p < 0.001). In further analysis of Caucasians, the variant NQO1 genotypes (CT and TT) were associated with a marginally increased lung cancer risk (OR = 1.19; 95% CI: 0.95-1.50). The elevated lung cancer risk was only evident in younger individuals (age <62 years old) (OR = 1.46; 95% CI: 1.04-2.05), women (OR = 1.89; 95% CI: 1.33-2.68), and never smokers (OR = 1.80; 95% CI: 1.03-3.13). Furthermore, we found a statistically significant trend in the development of lung cancer at an early age in women with increasing copies of the variant allele (p = 0.03). These results suggest that the NQO1 variant genotype may modulate lung cancer risk, especially in younger individuals (age < 62), women, and never smokers.
KW - Genetic polymorphism
KW - Lung cancer
KW - NQO1
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U2 - 10.1016/j.mrgentox.2004.12.010
DO - 10.1016/j.mrgentox.2004.12.010
M3 - Article
C2 - 15781212
AN - SCOPUS:15244350514
SN - 1383-5718
VL - 582
SP - 71
EP - 78
JO - Mutation Research - Genetic Toxicology and Environmental Mutagenesis
JF - Mutation Research - Genetic Toxicology and Environmental Mutagenesis
IS - 1-2
ER -