Meta-analysis of the NAD(P)H: quinine oxidoreductase 1 gene 609 C>T polymorphism with esophageal cancer risk

Association between the NAD(P)H: quinine oxidoreductase 1 (NQO1) gene 609 C>T polymorphism and esophageal cancer (EC) has been widely evaluated; however, the results are often irreproducible. We thus aimed to comprehensively evaluate this association through a meta-analysis. Data were extracted from 10 study populations involving 1390 EC patients and 1812 controls, and were analyzed using STATA software. Random-effects model was applied irrespective of between-study heterogeneity, which was assessed by the inconsistency index (I(2)) statistic. Publication bias was weighted by the funnel plot and Egger's test. Genotype distributions of the NQO1 gene 609 C>T polymorphism met Hardy-Weinberg equilibrium in controls for all studies. Allelic comparison indicated that NQO1 609 T allele conferred an increased risk (odds ratio [OR]=1.23; 95% confidence interval [CI]: 1.02-1.49; p=0.035), accompanying significant heterogeneity (I(2)=63.4%, p=0.003) and no publication bias (p(Egger)=0.391). This association was potentially enhanced in homozygous comparison (OR=1.58; 95% CI: 1.03-2.41; p=0.035; I(2)= 55.4%, p(heterogeneity)=0.017 and p(Egger)=0.461). Under dominant and recessive models, similar associations were obtained with an increased, although marginally significant risk. Subgroup analysis by ethnicity supported the risk profiles of the NQO1 gene 609 T allele and 609 TT genotype with EC in Eastern Asians, not in Europeans. Meta-regression analysis indicated that association between the NQO1 gene 609 C>T polymorphism and EC risk was significantly decreased with aging in case-patients (R(2)=-0.57; p=0.042). We expand previous studies by showing that the NQO1 gene 609 C>T polymorphism might contribute to EC occurrence, especially in Eastern Asians.