Liu Fei, Luo Limei, Wei Yonggang, Wang Wentao, Li Bo, Yan Lvnan, Wen Tianfu
Division of Liver Transplantation, Department of Liver and Vascular Surgery, West China Hospital, Sichuan University, 37 Guo Xue Road, Chengdu, 610041, Sichuan Province, China.
Tumour Biol. 2013 Feb;34(1):47-53. doi: 10.1007/s13277-012-0509-x. Epub 2012 Sep 13.
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.
NAD(P)H：醌氧化还原酶1（NQO1）是一种胞质黄素蛋白，可催化醌类化合物双电子还原为氢醌，从而保护细胞免受氧化损伤。NQO1基因609位点的单碱基替换（C→T）多态性会降低醌还原酶活性。因此，纯合子C609T NQO1多态性（rs1800566）缺乏酶活性可能在肿瘤发生中起关键作用。我们推测NQO1基因变异可能会改变个体对肝细胞癌（HCC）的易感性。为了验证该变异可能在HCC易感性中起作用这一假设，我们在中国人群中开展了一项基于医院的病例对照研究，纳入476例HCC患者和526例无癌对照。采用基质辅助激光解吸/电离飞行时间质谱法检测该多态性。结果显示，NQO1 C609T的变异等位基因和基因型在病例组中比对照组中更常见（P = 0.003和P = 0.024）。与NQO1 609CC基因型相比，变异型NQO1 609TT [校正比值比（OR）= 1.60，95%置信区间（CI）= 1.12 - 2.28]以及合并的NQO1 609TC/TT（校正OR = 1.37，95% CI = 1.04 - 1.80）基因型与HCC风险显著增加相关。此外，进行亚组分析时，我们发现年轻受试者、男性、乙肝表面抗原阳性个体、从不吸烟者、从不饮酒者以及无癌症家族史的受试者中风险增加更为明显。这些结果表明，NQO1 C609T多态性的存在可能是HCC遗传易感性的一个标志物。
