Increased risk of bladder cancer associated with a glutathione peroxidase 1 codon 198 variant
Increased risk of bladder cancer associated with a glutathione peroxidase 1 codon 198 variant
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DOI：
10.1097/01.ju.0000130942.40597.9d
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发表时间：
2004-08-01
影响因子：
6.6
通讯作者：
Kato, T
中科院分区：
文献类型：
--
作者：
Ichimura, Y;Habuchi, T;Kato, T
目的：谷胱甘肽过氧化物酶1基因（GPX 1）和锰超氧化物歧化酶基因（MnSOD）编码的主要抗氧化酶，解毒参与致癌作用的内源性活性氧。检测GPX 1和MnSOD基因多态性与膀胱移行细胞癌发病风险的关系。GPX 1第198位密码子亮氨酸（Leu）至脯氨酸（Pro）多态性的基因型，用聚合酶链反应（PCR）检测MnSOD基因外显子2的丙氨酸（Ala）→缬氨酸（瓦尔）多态性和56位密码子的异亮氨酸→苏氨酸多态性。结果：GPX 1基因型频率在病例组和对照组之间差异有显著性（P = 0.001），GPX 1基因型频率在病例组和对照组之间差异有显著性（P = 0.001）。Pro/Leu基因型与Pro/Pro基因型相比，膀胱癌的校正OR为2.63（95% CI 1.45至4.75，p = 0.001）。与Pro/Pro基因型相比，Pro/Leu基因型与晚期肿瘤分期显著相关（Ta-1 vs T2-4，OR 2.58，95%CI 1.07至6.18，p = 0.034），但与肿瘤分级无关。MnSOD多态性的分析没有提供显着的结果。结论：GPX 1 Pro/Leu基因型可显著增加膀胱癌的发病风险，且这种增加的风险可能受到Ala-9Val MnSOD多态性的影响。GPX 1基因型可能进一步影响膀胱癌的疾病状态。
Purpose: The glutathione peroxidase 1 gene (GPX1) and the manganese superoxide dismutase gene (MnSOD) encode the main antioxidant enzymes that detoxify endogenous reactive oxygen species involved in carcinogenesis. Polymorphisms of GPX1 and MnSOD genes, and the risk of transitional cell cancer of the bladder were tested.Materials and Methods: Genotypes of the leucine (Leu) to proline (Pro) polymorphism at codon 198 of GPX1, the alanine (Ala) to Valine (Val) polymorphism in exon 2 and the isoleucine to threonine polymorphism at codon 56 of MnSOD were determined by a polymerase chain reaction-restriction fragment length polymorphism technique in 213 patients and 209 normal controls.Results: There was a significant difference in GPX1 genotype frequency between the case and control groups (p = 0.001). The adjusted OR for bladder cancer was 2.63 for the Pro/Leu genotype compared with the Pro/Pro genotype (95% CI 1.45 to 4.75, p = 0.001). Compared with the Pro/Pro genotype the Pro/Leu genotype was significantly associated with advanced tumor stage (Ta-1 vs T2-4, OR 2.58, 95% CI 1.07 to 6.18, p = 0.034) but not with tumor grade. Analysis of the MnSOD polymorphism provided no significant results. However, in men with at least 1 Ala MnSOD allele the risk associated with the Pro/Leu GPX1 genotype increased up to 6.31 (95% CI 1.28 to 31.24, p = 0.024).Conclusions: The GPX1 Pro/Leu genotype may significantly increase the risk of bladder cancer and the increased risk may be modified by the Ala-9Val MnSOD polymorphism. The GPX1 genotype may further affect the disease status of bladder cancer.