A functional NQO1 609C>T polymorphism and risk of hepatocellular carcinoma in a Chinese population

NAD(P)H:quinone oxidoreductase 1 (NQO1) is a cytosolic flavoprotein that catalyzes the two-electron reduction of quinoid compounds into hydroquinones, thus protecting cells from oxidative damage. A single base substitution (C→T) polymorphism at 609 in the NQO1 gene reduces quinone reductase activity. Thus, the lack of enzymatic activity in the homozygous C609T NQO1 polymorphism (rs1800566) may play a pivotal role in tumor development. We hypothesized that a genetic variant in NQO1 may modify individual susceptibility to hepatocellular carcinoma (HCC). To test this hypothesis that the variant may play a role in HCC susceptibility, we conducted a hospital-based case-control study of 476 HCC patients and 526 cancer-free controls in a Chinese population. The matrix-assisted laser desorption/ionization time-of-flight mass spectrometry method was performed to detect the polymorphism. The results showed that the variant alleles and genotypes of NQO1 C609T were more common among cases than those among controls (P = 0.003 and P = 0.024). Compared with the NQO1 609CC genotype, there was a significantly greater risk of HCC associated with the variant NQO1 609TT [adjusted odds ratio (OR) = 1.60, 95 % confidence interval (CI) = 1.12-2.28] and combined NQO1 609TC/TT (adjusted OR = 1.37, 95 % CI = 1.04-1.80) genotypes. Moreover, when subgroup analyses were performed, we found that the increase in risk was more evident among younger subjects, men, HbsAg-positive individuals, never smokers, never drinkers, and subjects without family history of cancer. These results suggest that the presence of the NQO1 C609T polymorphism may be a marker of genetic susceptibility to HCC.