The NAD(P)H:quinone oxidoreductase I C609T polymorphism modifies the risk of Barrett esophagus and esophageal adenocarcinoma.
OBJECTIVE
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 = 0.22, 95% confidence interval = 0.07-0.76, P = 0.01) and a 6.2-fold decreased risk of esophageal adenocarcinoma (odds ratio = 0.16, 95% confidence intervals = 0.03-0.94, P = 0.04) compared with individuals with the TC and CC genotypes. No significant differences between groups were observed for the MnSOD polymorphism (P = 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.
di Martino
Erica
E
Molecular Epidemiology Unit, Centre for Epidemiology and Biostatistics, Leeds Institute for Genetics, Health and Therapeutics, University of Leeds, Leeds, United Kingdom.
Hardie
Laura J
LJ
Wild
Christopher P
CP
Gong
Yun Y
YY
Olliver
Joanna R
JR
Gough
Martin D
MD
Bird
Nigel C
NC
D000230:Adenocarcinoma / Q000201:enzymology / Q000235:genetics*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001471:Barrett Esophagus / Q000201:enzymology / Q000235:genetics*; D004938:Esophageal Neoplasms / Q000201:enzymology / Q000235:genetics*; D004942:Esophagitis, Peptic / Q000150:complications; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008875:Middle Aged; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors
D016660:NAD(P)H Dehydrogenase (Quinone); C447479:NQO1 protein, human