The NAD(P)H:quinone oxidoreductase I C609T polymorphism modifies the risk of Barrett esophagus and esophageal adenocarcinoma

Abstract

Purpose: The role of genetic susceptibility to esophageal adenocarcinoma and its precursor lesion Barrett esophagus has not been fully elucidated. This study investigated the effect of polymorphisms in the manganese superoxide dismutase (MnSOD) and NAD(P)H:quinone oxidoreductase 1 (NQO1) genes in modulating the risk of developing Barrett esophagus or esophageal adenocarcinoma. Methods: A total of 584 patients (146 esophagitis, 200 Barrett esophagus, 144 esophageal adenocarcinoma, and 94 controls) were genotyped for the MnSOD C14T and NQO1 C609T polymorphisms using polymerase chain reaction and restriction fragment length polymorphism analysis. Results: The NQO1 TT genotype was less common in Barrett esophagus (2.0%) and esophageal adenocarcinoma (1.4%) patients, compared with both esophagitis patients (7.6%) and controls (5.4%). After adjustment for sex, age, body mass index, reflux symptoms, and smoking status, patients with the homozygous TT genotype had a 4.5-fold decreased risk of developing Barrett esophagus (odds ratio ϭ 0.22, 95% confidence interval ϭ 0.07-0.76, P ϭ 0.01) and a 6.2-fold decreased risk of esophageal adenocarcinoma (odds ratio ϭ 0.16, 95% confidence intervals ϭ 0.03-0.94, P ϭ 0.04) compared with individuals with the TC and CC genotypes. No significant differences between groups were observed for the MnSOD polymorphism (P ϭ 0.289). Conclusions:Overall, the results of this study suggest that the NQO1 TT genotype may offer protection from reflux complications such as Barrett esophagus and esophageal adenocarcinoma. Genet Med 2007:9(6):341-347.

Relationships between single nucleotide polymorphisms of antioxidant enzymes and disease

“…There are conflicting reports on the potential association between the Ala allele and gastric cancer (Martin et al, 2005;Yi et al, 2010). Other forms of cancers studied include colorectal, oesophageal, pancreatic, ovarian and skin, with all reporting no association with SOD2 genotypes (di Martino et al, 2007;Funke et al, 2009;Han et al, 2007;Johnatty et al, 2007;Li et al, 2002;Martin et al, 2005;Murphy et al, 2007;Sun et al, 2009). …”

“…Twenty-one studies have investigated the relationship between the SOD2 Ala16Val SNP and other cancers (di Martino et al, 2007;Han et al, 2007;Hirvonen et al, 2002;Ho et al, 2006;Hung et al, 2004;Ichimura et al, 2004;Johnatty et al, 2007;Koistinen et al, 2006;Landi et al, 2007;Li et al, 2002;Lightfoot et al, 2006;Lin et al, 2003;Liu et al, 2004;Mak et al, 2007;Martin et al, 2005;Murphy et al, 2007;Sun et al, 2009;Wang et al, 2004Wang et al, , 2006Young et al, 2006;Zejnilovic et al, 2009). Wang et al (2004) found that individuals with the Val allele had an increased risk of lung cancer if there was low or no asbestos exposure compared to high exposure (OR 2.14, 95% CI 1.52-3.01), although the small number in the high asbestos exposure group limited the validity of the findings.…”

Different Association of Manganese Superoxide Dismutase Gene Polymorphisms with Risk of Prostate, Esophageal, and Lung Cancers: Evidence from a Meta-analysis of 20,025 Subjects

“…Briefly, of the 22 studies (Wang et al, 2001;Woodson et al, 2001;Lin et al, 2003;Liu et al, 2004;Wang et al, 2004;Li et al, 2005;Taufer et al, 2005;Ho et al, 2006;Choi et al, 2007;di Martino et al, 2007;Ergen et al, 2007;Kang et al, 2007;Arsova-Sarafinovska et al, 2008;Iguchi et al, 2008;Mikhak et al, 2008;Bica et al, 2009;Cheng et al, 2009;Iguchi et al, 2009;Sun et al, 2009;Zejnilovic etal., 2009), the sample size ranged between 100 and 3,030, and there were twelve studies on prostate cancer, four studies on esophageal cancer, and six studies on lung cancer. All studies, except for five of them (Taufer et al, 2005;Bica et al, 2009;Sun et al, 2009;Zejnilovic et al, 2009), indicated that the distribution of genotypes in the controls was consistent with HardyWeinberg equilibrium, while only one study conducted by Lin et al (2003) contained no data for Hardy-Weinberg equilibrium.…”

Clinical puzzle: Barrett’s oesophagus

“…Recent data have suggested an association between polymorphisms of two detoxifying enzymes [NAD(P)H:quinone oxidoreductase and glutathione S-transferase P1] and the risk of developing Barrett's and OAC (Casson et al, 2006;di Martino et al, 2007;Redon et al, 2006). Another candidate genetic marker of Barrett's susceptibility is cyclin D1, whose function as part of the cell cycle machinery is to allow progression to S-phase.…”