Genetic polymorphism 609C>T in NAD(P)H:quinone oxidoreductase 1 enhances the risk of proximal colon cancer.
Gastrointestinal (GI) cancer is responsible for the majority of deaths among all types of cancer. Lifestyle factors may not only be the main risk factor for GI cancer but reactive oxygen species (ROS) may also be involved. The single-nucleotide polymorphisms (SNPs) 609C>T (rs1800566) and 465C>T (rs1131341) in the
quinone oxidoreductase 1 (NQO1) gene lead to a decline in NQO1 enzyme activity. NQO1 catalyzes the two-electron reduction of quinones to hydroquinones, thereby preventing the formation of ROS. Such polymorphisms in NQO1 may increase the risk of GI cancer. The aim of this study was to evaluate the influence of the SNPs rs1800566 and rs1131341 in the NQO1 gene on the risk of GI cancer in the Netherlands. Real-time polymerase chain reaction techniques were conducted to determine the NQO1 genotypes of 1457 patients with GI cancer and 1457 age- and gender-matched controls in a case-control study. Binary logistic regression analyses showed no statistically significant difference in genotype distributions between patients and controls: odds ratios (ORs) with 95% confidence interval (CI) for rs1800566 were 1.09 (0.93-1.28) and 1.17 (0.77-1.77) for the CT and TT genotypes, respectively. ORs for rs1131341 CT and TT genotypes were 1.21 (0.90-1.63) and 0.54 (0.05-5.94), respectively. For rs1800566, a significant association between the CT genotype and proximal colon cancer was detected (OR=1.60; 95% CI=1.09-2.35). The NQO1*2 T allele of SNP rs1800566 was found associated with an increased risk for proximal colorectal cancer, whereas SNP rs1131341 was rare in our Dutch population and was not associated with GI cancer.
Department of Gastroenterology, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands.
Jolien J M
JJ
Freriksen
Department of Gastroenterology, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands.
Jody
J
Salomon
Department of Gastroenterology, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands.
Hennie M J
HM
Roelofs
Department of Gastroenterology, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands.
Rene H M
RH
Te Morsche
Department of Clinical Chemistry, Canisius-Wilhelmina Ziekenhuis, Nijmegen, The Netherlands.
Jos W J
JW
van der Stappen
Department of Gastroenterology, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands.
Polat
P
Dura
Department of Gastroenterology, Hospital Gelderse Vallei, Ede, The Netherlands.
Ben J M
BJ
Witteman
Department of Otorhinolaryngology, Head and Neck Surgery, Maastricht University Medical Center, Maastricht, The Netherlands.
Martin
M
Lacko
Department of Gastroenterology, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands.
Wilbert H M
WH
Peters
D000483:Alleles; D016022:Case-Control Studies; D003110:Colonic Neoplasms / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology*; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000235:genetics*; D009426:Netherlands; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D012306:Risk
D016660:NAD(P)H Dehydrogenase (Quinone); C447479:NQO1 protein, human