Laboratory of Protein Engineering and Bio-active Molecules, National Institute of Applied Science and Technology - University of Carthage, Tunis, Tunisia.
Urology Department, Charles Nicolle Hospital, Tunis, Tunisia.
Mol Genet Genomic Med. 2021 Nov;9(11):e1819. doi: 10.1002/mgg3.1819. Epub 2021 Sep 22.
NAD (P) H: quinone oxidoreductase (1) (NQO1-HGNC: 2874) and myeloperoxidase (MPO-HGNC: 7218) are two enzymes involved in phase II of the xenobiotic metabolism pathway.
In this study, a case-control analysis was conducted to investigate the relationship between genetic variations in the NQO1 (C609T, rs1800566; IVS1-27 C >G, rs689452) and MPO (G463A, rs2333227) genes and the risk for bladder cancer among Tunisian population.
We have found that the MPO 463GA genotype was associated with a decreased risk of developing bladder cancer (p = 0.049; OR = 0.696; 95% CI 0.484-0.999). In contrast, we have found that the NQO1 609CT genotype could increase the risk of bladder cancer patients (p = 0.0039; OR = 1.454; 95% CI = 1.017-2.078). Moreover, patients with "NQO1 609 CT/IVS1-27 CG" genotype show a 2.180-fold increasing risk for developing bladder cancer in comparison to the control group with wild genotype. This OR is estimated at 5.6-fold in smokers patients with "NQO1 609 CT/IVS1-27 CG" genotype. Lastly, study findings suggest that the NQO1 IVS-27 *CG genotype (rs689452) is associated with a risk of progression to muscle invasive bladder cancer.
Our study suggests that environmental risk factors in association to NQO1 genotypes (NQO1 609 CT/IVS1-27 CG) play an important role in the development of bladder cancer in Tunisian population.
烟酰胺腺嘌呤二核苷酸(P):醌氧化还原酶 1(1)(NQO1-HGNC:2874)和髓过氧化物酶(MPO-HGNC:7218)是两种参与异生物质代谢途径第二阶段的酶。
本研究采用病例对照分析方法,研究了 NQO1(C609T,rs1800566;IVS1-27 C > G,rs689452)和 MPO(G463A,rs2333227)基因的遗传变异与突尼斯人群膀胱癌风险之间的关系。
我们发现 MPO 463GA 基因型与膀胱癌发病风险降低相关(p=0.049;OR=0.696;95%CI 0.484-0.999)。相反,我们发现 NQO1 609CT 基因型可增加膀胱癌患者的风险(p=0.0039;OR=1.454;95%CI 1.017-2.078)。此外,与野生基因型对照组相比,携带“NQO1 609 CT/IVS1-27 CG”基因型的患者发生膀胱癌的风险增加 2.180 倍。在携带“NQO1 609 CT/IVS1-27 CG”基因型的吸烟者患者中,这种 OR 估计为 5.6 倍。最后,研究结果表明,NQO1 IVS-27*CG 基因型(rs689452)与膀胱癌进展为肌肉浸润性膀胱癌的风险相关。
本研究表明,环境危险因素与 NQO1 基因型(NQO1 609 CT/IVS1-27 CG)在突尼斯人群膀胱癌的发生中起重要作用。