中国神经再生研究(英文版)

中国神经再生研究(英文版) ›› 2013, Vol. 8 ›› Issue (26): 2468-2477.doi: 10.3969/j.issn.1673-5374.2013.26.008

• 原著:脑损伤修复保护与再生 • 上一篇    下一篇

脑胶质瘤发病与X射线交叉互补修复基因1多态性的Meta分析

  

  • 收稿日期:2013-06-03 修回日期:2013-08-25 出版日期:2013-09-15 发布日期:2013-09-15
  • 基金资助:

    吉林大学基础研究项目（No. 450060445246）；吉林省高技术产业发展项目(No.20090633)；吉林省科学研究基金（No. 20130206001YY, 20120713 and 200905169）；长春市科学研究基金（No. 12SF29）

Correlation between X-ray cross-complementing group 1 polymorphisms and the onset risk of glioma A meta-analysis

Xinquan Gu1, Hongyan Sun2, Liping Chang3, Ran Sun2, Hongfeng Yang4, Xuewen Zhang2, Xianling Cong2, 4   

  1. 1 Department of Urinary Surgery, China-Japan Union Hospital of Jilin University, Changchun 130033, Jilin Province, China

    2 Tissue Bank, China-Japan Union Hospital of Jilin University, Changchun 130033, Jilin Province, China

    3 Department of Cardiopathy, the Affiliated Hospital of Changchun University of Chinese Medicine, Changchun 130021, Jilin Province, China

    4 Department of Dermatology, China-Japan Union Hospital of Jilin University, Changchun 130033, Jilin Province, China
  • Received:2013-06-03 Revised:2013-08-25 Online:2013-09-15 Published:2013-09-15
  • Contact: Xianling Cong, Ph.D., Associate professor, Tissue Bank, China-Japan Union Hospital of Jilin University, Changchun 130033, Jilin Province, China; Department of Dermatology, China-Japan Union Hospital of Jilin University, Changchun 130033, Jilin Province, China, congxl888@ hotmail.com.
  • About author:Xinquan Gu, Ph.D., Professor. Xinquan Gu and Hongyan Sun contributed equally to this article.
  • Supported by:

    The Fundamental Research Funds for Jilin University in China, No. 450060445246; the High-Tech Industrial Development Project of Jilin Province in China, No. 20090633; and the Scientific Research Foundation of Jilin Province in China, No. 20130206001YY, 20120713 and 200905169; the Scientific Research Foundation of Changchun in China, No. 12SF29.

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摘要：

目的：采用Meta分析方法探讨X射线交叉互补修复基因1（XRCC1）399位点，194位点，280位点基因多态性与胶质瘤发病风险的关系。
资料来源：分别以“glioma”，“polymorphism” and “XRCC1 or X-ray repair cross complementing group 1”和“胶质瘤”，“基因多态性”，“XRCC1”为主题词和关键词检索英文数据库Pubmed，EMBASE和中文数据库CNKI和万方中2000-01/2012-08发表的相关论文，并对文章的参考文献回溯及手工检索。
资料选择：纳入资料完整的研究XRCC1基因多态性与胶质瘤发病相关的病例对照研究，胶质瘤均经病理证实，研究对象无血缘关系。纳入文献由两名作者进行筛选，提取各基因型的统计指标OR值(95%CI)或相关数据。应用Review Manager 5.0软件进行meta分析，分别假定显性遗传模型和隐形遗传模型，同时对病例组和对照组纯合子突变基因型频率和突变型基因频率与胶质瘤发病的关系进行探讨，根据异质性检验结果，选用固定效应模型或随机效应模型计算合并OR值和95%CI，并进行敏感性分析，应用Stata 12.0软件进行Egger’s test评价发表文章偏倚。
结局评价指标：XRCC1基因399位点，194位点，280位点多态性与胶质瘤发病风险的关系，并以不同的种族为依据进行亚组分析。
结果：最终纳入12篇文献，11篇涉及XRCC1基因399位点多态性与胶质瘤发病风险的分析，meta分析结果显示，在显性遗传模型中，联合基因突变型（Gln/Gln + Gln/Arg）与野生基因型Arg/Arg相比，能够增加胶质瘤发病风险（OR=1.26, 95%CI=1.03-1.54, P=0.02）。种族分层分析显示，显性遗传模型中，联合基因突变型（Gln/Gln + Gln/Arg）与野生基因型Arg/Arg相比，能够增加亚洲人胶质瘤发病风险（OR= 1.40, 95%CI=1.10-1.78, P=0.007）；在隐性遗传模型得到同样的结果（OR=1.46, 95%CI=1.04-2.45, P=0.03），纯合突变基因型Gln/Gln合并OR值为1.69, 95%CI=1.17-2.45，P=0.005，表明Gln/Gln能增加亚洲人患胶质瘤的风险。XRCC1基因194位点和280位点多态性与胶质瘤发病风险相关文献分别为8篇和4篇，在显性遗传模型和隐性遗传模型中均未发现XRCC1基因194位点和280位点变异与胶质瘤发病风险相关。
结论：XRCC1基因399位点多态性与胶质瘤易感性相关，特别是在亚洲人群中；而XRCC1基因194位点和280位点突变与胶质瘤发病无关联。

关键词: 神经再生, 临床实践, 胶质瘤, X射线交叉互补修复基因1, 基因多态性, Meta分析, 易感性, 发病风险, 基因突变, 基金资助文章

Abstract:

OBJECTIVE: To evaluate the association of X-ray cross-complementing group 1 (XRCC1) Arg399Gln, Arg194Trp and Arg280His polymorphisms with the risk of glioma.
DATA SOURCES: A systematic literature search of papers published from January 2000 to August 2012 in PubMed, Embase, China National Knowledge Infrastructure database, and Wanfang da-tabase was performed. The key words used were “glioma”, “polymorphism”, and “XRCC1 or X-ray repair cross-complementing group 1”. References cited in the retrieved articles were screened manually to identify additional eligible studies.
STUDY SELECTION: Studies were identified according to the following inclusion criteria: case-control design was based on unrelated individuals; and genotype frequency was available to estimate an odds ratio (OR) and 95% confidence interval (CI). Meta-analysis was performed for the selected studies after strict screening. Dominant and recessive genetic models were used and the relationship between homozygous mutant genotype frequencies and mutant gene frequency and glioma incidence was investigated. We chose the fixed or random effect model according to the heterogeneity to calculate OR and 95%CI, and sensitivity analyses were conducted. Publication bias was examined using the inverted funnel plot and the Egger’s test using Stata 12.0 software.
MAIN OUTCOME MEASURES: Association of XRCC1 Arg399Gln, Arg194Trp, and Arg280His polymorphisms with the risk of glioma, and subgroup analyses were performed according to differ-ent ethnicities of the subjects.
RESULTS: Twelve articles were included in the meta-analysis. Eleven of the articles were concerned with the Arg399Gln polymorphism and glioma onset risk. Significantly increased glioma risks were found only in the dominant model (Gln/Gln + Gln/Arg versus Arg/Arg: OR = 1.26, 95%CI = 1.03–1.54, P = 0.02). In the subgroup analysis by ethnicity, significantly increased risk was found in Asian subjects in the recessive (OR = 1.46, 95%CI = 1.04–2.45, P = 0.03) and dominant models (OR = 1.40, 95%CI = 1.10–1.78, P = 0.007), and homozygote contrast (OR = 1.69, 95%CI = 1.17–2.45, P = 0.005), but not in Caucasian sub-jects. For association of the Arg194Trp (eight studies) and Arg280His (four studies) polymorphisms with glioma risk, the meta-analysis did not reveal a significant effect in the allele contrast, the recessive genetic model, the dominant genetic model, or homozygote contrast.
CONCLUSION: The XRCC1 Arg399Gln polymorphism may be a biomarker of glioma susceptibility, es-pecially in Asian populations. The Arg194Trp and Arg280His polymorphisms were not associated with overall glioma risk.

Key words: neural regeneration, meta-analysis, glioma, X-ray cross-complementing group 1, gene polymorphism, meta-analysis, susceptibility, onset risk, gene mutation, grants-supported paper, neuroregeneration