Department of Urology, Tung's Taichung MetroHarbor Hospital, Taichung County, Taiwan, ROC.
Division of General Surgery, Department of Surgery, Shuang Ho Hospital, Taipei Medical University, Taipei, Taiwan, ROC; Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan, ROC.
J Chin Med Assoc. 2014 Feb;77(2):83-8. doi: 10.1016/j.jcma.2013.10.005. Epub 2013 Dec 5.
NAD(P)H: quinine oxidoreductase (NQO1) plays an important role in the metabolism of several carcinogens contained in cigarettes. Inducible nitric oxide synthase (iNOS) expression had been detected in urinary bladder tumors. The aim of this study was to investigate the interaction of iNOS and NQO1 on bladder cancer (BC) risk stratified by cigarette smoking status.
A total of 159 BC patients and 150 cancer-free controls were recruited from December 2003 to November 2004. Genotyping of NQO1 rs1800566 polymorphism and iNOS (CCTTT)n pentanucleotide repeat polymorphism was determined using the polymerase chain reaction-restricted fragment length polymorphism and sequencing method. The odds ratio and 95% confidence interval (CI) were calculated as a measure of the joint effect of NQO1 rs1800566 and iNOS (CCTTT)n polymorphisms on BC risk among cigarette smokers.
Compared with study participants carrying the C/C genotype of NQO1 gene, those with C/T and T/T genotypes had a significantly increased BC risk of 1.8 (95% CI = 1.1-2.9). Among cigarette smokers, those who carried the 12-repeat allele of iNOS (CCTTT)n polymorphism had a significantly increased BC risk of 2.7 (95% CI = 1.0-6.7). Furthermore, a significant combined effect of the C/T and T/T genotypes of NQO1gene and the 12-repeat allele of iNOS (CCTTT)n repeat polymorphism on BC was found among cigarette smokers (odds ratio = 4.4, 95% CI = 1.3-14.9).
Our findings suggest that a significant combined effect of NQO1 C/T and T/T genotypes and the 12-repeat allele of iNOS (CCTTT)n polymorphism on BC exists, especially in those with the habit of cigarette smoking.
NAD(P)H：醌氧化还原酶（NQO1）在香烟中含有的几种致癌物质的代谢中发挥重要作用。诱导型一氧化氮合酶（iNOS）在膀胱癌中已被检测到。本研究旨在探讨 iNOS 和 NQO1 在根据吸烟状态分层的膀胱癌（BC）风险中的相互作用。
本研究共纳入 2003 年 12 月至 2004 年 11 月期间的 159 名膀胱癌患者和 150 名无癌对照。采用聚合酶链反应限制性片段长度多态性和测序法检测 NQO1 rs1800566 多态性和 iNOS（CCTTT）n 五核苷酸重复多态性的基因型。计算比值比（OR）和 95%置信区间（CI）作为衡量 NQO1 rs1800566 和 iNOS（CCTTT）n 多态性在吸烟者中对 BC 风险的联合作用的指标。
与携带 NQO1 基因 C/C 基因型的研究参与者相比，C/T 和 T/T 基因型的 BC 风险显著增加，为 1.8（95%CI=1.1-2.9）。在吸烟者中，携带 iNOS（CCTTT）n 多态性 12 重复等位基因的个体 BC 风险显著增加，为 2.7（95%CI=1.0-6.7）。此外，在吸烟者中还发现 NQO1 基因 C/T 和 T/T 基因型与 iNOS（CCTTT）n 重复多态性 12 重复等位基因之间存在显著的联合作用，对 BC 的影响为 4.4（95%CI=1.3-14.9）。
我们的研究结果表明，NQO1 C/T 和 T/T 基因型与 iNOS（CCTTT）n 多态性 12 重复等位基因对 BC 存在显著的联合作用，尤其是在有吸烟习惯的人群中。
