DNA repair gene hOGG1 codon 326 and XRCC1 codon 399 polymorphisms and bladder cancer risk in a Japanese population
DNA repair gene hOGG1 codon 326 and XRCC1 codon 399 polymorphisms and bladder cancer risk in a Japanese population
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DOI：
10.1093/jjco/hym176
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发表时间：
2008-03-01
影响因子：
2.4
通讯作者：
Kuroda, Yoshiki
中科院分区：
文献类型：
--
作者：
Arizono, Katsuyuki;Osada, Yukio;Kuroda, Yoshiki
背景：膀胱癌是美国最常见的泌尿系统恶性肿瘤。吸烟会导致DNA氧化损伤并诱发膀胱癌。碱基切除修复（BER）是修复氧化DNA损伤的一种非常重要的机制。有许多酶参与BER。人氧鸟嘌呤糖基化酶1（hOGG 1）和X射线修复交叉互补1（XRCC 1）是BER的酶基因。实际上，hOGG 1密码子326多态性与肺癌、食管癌和胃癌的风险相关。另一方面，在几种XRCC 1基因多态性中，密码子399多态性被报道可以降低膀胱癌的风险并增加肺癌的风险。方法：我们研究了hOGG 1密码子326和XRCC 1密码子399基因多态性与膀胱癌风险之间的关系。在这项研究中，我们招募了251例膀胱癌患者和251名健康对照，以评估hOGG 1密码子326和XRCC 1密码子399多态性对膀胱癌的影响。结果：病例组hOGG 1第326位密码子Cys/Cys基因型频率明显高于对照组，差异有统计学意义（P < 0. 05）。与Ser/Ser相比，校正比值比（OR）为1.85（95% CI：1.12-3.03; p = 0.02），与Ser/Ser + Ser/Cys相比，校正比值比（OR）为2.05（95% CI：1.36-3.08; p = 0.01）。此外，当评估吸烟状况时，非吸烟者的校正OR（Cys/Cys vs Ser/Ser + Ser/Cys）高达2.78（95%CI：1.39-5.60; p < 0.01）。XRCC 1第399位密码子基因型Gln/Gln多态性在对照组显著高于病例组（P < 0. 05），但与Alg/Alg + Alg/Gln相比差异无统计学意义。结论：hOGG 1密码子326和XRCC 1密码子399多态性是膀胱癌的危险因素。
Background: Bladder cancer is the most common urologic malignancy in the USA. Tobacco smoking generates oxidative DNA damage and induces bladder cancer. Base excision repair (BER) is a very important mechanism for repairing oxidative DNA damage. There are many enzymes involved in BER. Human oxoguanine glycosylase 1 (hOGG1) and X-ray repair cross-complementing 1 (XRCC1) are enzyme genes of BER. Actually, the hOGG1 codon 326 polymorphism was associated with the risk of lung oesophagus and stomach cancer. On the other hand, among several XRCC1 gene polymorphisms, codon 399 polymorphism was reported to reduce the risk of bladder cancer and raise the risk of lung cancer.Methods: We examined the association between the genetic polymorphisms of hOGG1 codon 326 and XRCC1 codon 399 and bladder cancer risk. In this study, we recruited 251 bladder cancer cases and 251 healthy controls to evaluate the effect of hOGG1 codon 326 and XRCC1 codon 399 polymorphisms on bladder cancer. We detected genotypes by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method.Results: The frequencies of the hOGG1 codon 326 genotypes Cys/Cys was significantly higher in the cases than in the controls. Adjusted odds ratio (OR) was 1.85 (95% CI: 1.12-3.03; p = 0.02) compared with Ser/Ser, and was 2.05 (95% CI: 1.36-3.08; p = 0.01) compared with Ser/Ser + Ser/Cys. In addition, when evaluated with smoking status, the adjusted OR (Cys/Cys versus Ser/Ser + Ser/Cys) ran up to 2.78 (95% CI: 1.39-5.60; p < 0.01) among non-smokers. For the XRCC1 polymorphism, the Gln/Gln of XRCC1 codon 399 genotype was statistically higher in the controls than in the cases though compared with Alg/Alg + Alg/Gln. The adjusted OR was 0.45 (95% CI: 0.21-0.99; p = 0.05), and was lifted up to 0.37 (95% CI: 0.14-0.98; p = 0.05) among smokers.Conclusion: It is indicated that the hOGG1 codon 326 and XRCC1 codon 399 polymorphisms are risk factors of bladder cancer.