Interactive effect of smoking and NQO1 haplotypes on lung cancer risk.
The role of genetic polymorphisms of
quinone oxidoreductase 1 (NQO1), which is known to be related to carcinogen metabolism and oxidative status, was evaluated for lung cancer development. The genotypes of two NQO1 polymorphisms, namely, IVS1-27C>G and Ex6+40C>T, were determined in 616 lung cancer cases and 616 lung cancer-free controls and haplotypes composed of the two polymorphisms were estimated. In the evaluation of the effect of the NQO1 genotypes or diplotypes, we did not find any significant association with lung cancer risk after adjusting for body mass index and smoking status. However, when we evaluated the effect of the NQO1 diplotypes for lung cancer risk in combination with smoking, smokers without the C-T/C-T diplotype showed a significantly increased risk of lung cancer compared with nonsmokers without the C-T/C-T diplotype (adjusted OR, 2.2; 95% CI, 1.67-3.02), and smokers with the C-T/C-T diplotype showed the highest OR of lung cancer (adjusted OR, 2.7; 95% CI, 1.78-4.21). Moreover, a trend test showed an additive interaction between smoking and the NQO1 C-T/C-T diplotype (P trend < 0.01). The additive effect of smoking and the NQO1 C-T/C-T diplotype was more apparent in squamous cell carcinoma, although this effect was statistically significant in all lung cancer cell types (all cell types, P trend < 0.05). This result suggests that haplotypes of the NQO1 gene play an important role in the development of lung cancer by interaction with smoking.
Department of Environmental Health, Graduate School of Public Health, Seoul National University, Seoul, Korea.
Jin Hee
0000-0003-1204-7079
JH
Kim
Department of Preventive Medicine, Seoul National University College of Medicine, Seoul, Korea. ; Institute of Environmental Medicine, Seoul National University Medical Research Center, Seoul, Korea.
Yun-Chul
0000-0001-9010-7271
YC
Hong
D000368:Aged; D002289:Carcinoma, Non-Small-Cell Lung / Q000453:epidemiology / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D008175:Lung Neoplasms / Q000453:epidemiology / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D012306:Risk; D055752:Small Cell Lung Carcinoma / Q000453:epidemiology / Q000235:genetics*; D012907:Smoking / Q000009:adverse effects*
D016660:NAD(P)H Dehydrogenase (Quinone); C447479:NQO1 protein, human
Interaction; Lung Cancer Risk; NQO1 Polymorphism; Smoking