日本人群中DNA修复基因hOGG1第326密码子和XRCC1第399密码子多态性与膀胱癌风险

DNA repair gene hOGG1 codon 326 and XRCC1 codon 399 polymorphisms and bladder cancer risk in a Japanese population.

作者信息

Arizono Katsuyuki, Osada Yukio, Kuroda Yoshiki

机构信息

Department of Public Health, Faculty of Medicine, University of Miyazaki, 5200 Kihara Kiyotake, Miyazaki, 889-1692 Japan.

出版信息

Jpn J Clin Oncol. 2008 Mar;38(3):186-91. doi: 10.1093/jjco/hym176. Epub 2008 Feb 12.

DOI:10.1093/jjco/hym176

PMID:18272472

Abstract

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.

摘要

背景

膀胱癌是美国最常见的泌尿系统恶性肿瘤。吸烟会导致氧化性DNA损伤并诱发膀胱癌。碱基切除修复（BER）是修复氧化性DNA损伤的重要机制。BER涉及多种酶。人氧鸟嘌呤糖基化酶1（hOGG1）和X射线修复交叉互补蛋白1（XRCC1）是BER的酶基因。实际上，hOGG1密码子326多态性与肺癌、食管癌和胃癌风险相关。另一方面，在几种XRCC1基因多态性中，据报道密码子399多态性可降低膀胱癌风险并增加肺癌风险。

方法

我们研究了hOGG1密码子326和XRCC1密码子399的基因多态性与膀胱癌风险之间的关联。在本研究中，我们招募了251例膀胱癌患者和251名健康对照，以评估hOGG1密码子326和XRCC1密码子399多态性对膀胱癌的影响。我们采用聚合酶链反应-限制性片段长度多态性（PCR-RFLP）方法检测基因型。

结果

病例组中hOGG1密码子326基因型Cys/Cys的频率显著高于对照组。与Ser/Ser相比，调整后的优势比（OR）为1.85（95%置信区间：1.12 - 3.03；p = 0.02），与Ser/Ser + Ser/Cys相比为2.05（95%置信区间：1.36 - 3.08；p = 0.01）。此外，按吸烟状况评估时，非吸烟者中调整后的OR（Cys/Cys与Ser/Ser + Ser/Cys相比）高达2.78（95%置信区间：1.39 - 5.60；p < 0.01）。对于XRCC1多态性，尽管与Arg/Arg + Arg/Gln相比，XRCC1密码子399基因型Gln/Gln在对照组中的比例在统计学上高于病例组。调整后的OR为0.45（95%置信区间：0.21 - 0.99；p = 0.05），吸烟者中该值升至0.37（95%置信区间：0.14 - 0.98；p = 0.05）。