Meta-Analysis of the NAD(P)H: Quinine Oxidoreductase 1 Gene 609 C>T Polymorphism with Esophageal Cancer Risk

Abstract

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.

NAD(P)H: Quinone Oxidoreductase 1 (NQO1) C609T Gene Polymorphism Association with Digestive Tract Cancer: A Meta-analysis

“…In previous meta-analysis study, Wang et al (2012) and his colleagues' meta-analysis study also showed that the NQO1 gene 609 C> T polymorphism might contribute to esophageal cancer occurrence, especially in Eastern Asians, but in our study, no significantly different was observed in Caucasians or Asians. For colorectal cancer, no significant associations were found between NQO1 DOI:http://dx.doi.org/10.7314/APJCP.2013.14.4.2349 NQO1 C609T Gene Polymorphism andDigestive Tract Cancer: A Meta-analysis C609T polymorphism and colorectal cancer risk, but in the subgroup analysis by ethnicity; significant associations were observed for colorectal cancer in Caucasians, which was similar with previous meta-analysis study (Zhou et al, 2011;Chen et al, 2012).…”

Systematic review/Meta-analysis NQO1 C609T polymorphism and colorectal cancer susceptibility: a meta-analysis

“…It has been reported that the NQO1 C609T polymorphism is associated with the risk of many types of malignancies, such as cancers of the stomach [26], breast [27] and esophagus [28]. However, a meta-analysis by Guo et al .…”

The NAD(P)H: Quinine Oxidoreductase 1 (NQO1) Gene 609 C>T Polymorphism is Associated with Gastric Cancer Risk: Evidence from a Case-control Study and a Meta-analysis

“…Animal models using the NQO1-knockout mice suggested that the NQO1 gene deficiency increased susceptibility to cancer (Long et al, 2000;Iskander et al, 2005). Recently, an exonic polymorphism, C609T (also known as Pro187Ser) in NQO1 gene has been identified and widely evaluated in various malignancies such as esophageal cancer (Wang et al, 2012), Leukemia (Han et al, 2013) and Bladder…”