Interactive Effect of Smoking and NQO1 Haplotypes on Lung Cancer Risk

다국어 초록 (Multilingual Abstract)

The role of genetic polymorphisms of NAD(P)H:quinone oxidoreductase 1 (NQO1), which isknown to be related to carcinogen metabolism and oxidative status, was evaluated forlung 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 cancerfreecontrols and haplotypes composed of the two polymorphisms were estimated. In theevaluation of the effect of the NQO1 genotypes or diplotypes, we did not find anysignificant association with lung cancer risk after adjusting for body mass index andsmoking status. However, when we evaluated the effect of the NQO1 diplotypes for lungcancer risk in combination with smoking, smokers without the C-T/C-T diplotype showed asignificantly increased risk of lung cancer compared with nonsmokers without the C-T/C-Tdiplotype (adjusted OR, 2.2; 95% CI, 1.67-3.02), and smokers with the C-T/C-T diplotypeshowed the highest OR of lung cancer (adjusted OR, 2.7; 95% CI, 1.78-4.21). Moreover, atrend test showed an additive interaction between smoking and the NQO1 C-T/C-Tdiplotype (Ptrend < 0.01). The additive effect of smoking and the NQO1 C-T/C-T diplotypewas more apparent in squamous cell carcinoma, although this effect was statisticallysignificant in all lung cancer cell types (all cell types, Ptrend < 0.05). This result suggests thathaplotypes of the NQO1 gene play an important role in the development of lung cancer byinteraction with smoking.

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