The NQO1 C609T polymorphism and risk of lung cancer: a meta-analysis

Objective: NAD(P)H: quinone oxidoreductase 1 (NQO1) is a cytosolic flavoprotein that catalyzes the two-electron reduction of quinoid compounds into hydroquinones. A single base substitution (CgT) polymorphism at 609 in the NQO1 gene reduces quinone reductase activity. Published data on the association between NQO1 C609T polymorphism and lung cancer risk are conflicting. Methods: To derive a more precise estimation of the relationship, a meta-analysis was performed. Results: A total of 23 studies including 5,575 cases and 9,132 controls were assessed. The pooled result showed that the NQO1 polymorphism was not associated with a clear increased risk of lung cancer (OR = 1.009, 95% CI: 0.943-1.078; P heterogeneity=0.049). In the subgroup analysis by ethnicity, no clear increased risk was found among Asians for TT/CT versus CC (OR = 1.005; 95% CI = 0.890-1.135; Pheterogeneity=0.024). However, the TT and CT genotypes combined were associated with significantly increased risk of lung cancer in Chinese (OR = 1.237, 95% CI: 1.029-1.486; Pheterogeneity=0.061) among whom the variant allele is common. The variant genotype of NQO1 was also associated with modestly increased risk of lung cancer among white populations (OR = 1.017, 95% CI: 0.936-1.105; Pheterogeneity=0.101). However, no significant association was found in Africans with all genetic models. Conclusions: Our meta-analysis suggests that the variant NQO1 C609T genotype may affect individual susceptibility to lung cancer. This meta- analysis suggests that the NQO1 609T allele is a low penetrant risk factor for developing lung cancer in Chinese.