祁荣, 马业罡, 刘峥嵘, 刘大为, 孙晓玲, 孙中芙, 尹娇杨. 中国人DNA修复基因XRCC1 Pro206Pro和Gln632Gln单核苷酸多态与肺癌发生风险[J]. 中国肿瘤临床, 2007, 34(22): 1266-1269.
引用本文: 祁荣, 马业罡, 刘峥嵘, 刘大为, 孙晓玲, 孙中芙, 尹娇杨. 中国人DNA修复基因XRCC1 Pro206Pro和Gln632Gln单核苷酸多态与肺癌发生风险[J]. 中国肿瘤临床, 2007, 34(22): 1266-1269.
Qi Rong, Ma Yegang, Liu Zhengrong, Liu Dawei, Sun Xiaoling, Sun Zhongfu, Yin Jiaoyang. The Pro206Pro and Gln632Gln Polymorphisms in DNA Repair Gene XRCC1 and Genetic Susceptibility to Lung Cancer in the Chinese Population[J]. CHINESE JOURNAL OF CLINICAL ONCOLOGY, 2007, 34(22): 1266-1269.
Citation: Qi Rong, Ma Yegang, Liu Zhengrong, Liu Dawei, Sun Xiaoling, Sun Zhongfu, Yin Jiaoyang. The Pro206Pro and Gln632Gln Polymorphisms in DNA Repair Gene XRCC1 and Genetic Susceptibility to Lung Cancer in the Chinese Population[J]. CHINESE JOURNAL OF CLINICAL ONCOLOGY, 2007, 34(22): 1266-1269.

中国人DNA修复基因XRCC1 Pro206Pro和Gln632Gln单核苷酸多态与肺癌发生风险

The Pro206Pro and Gln632Gln Polymorphisms in DNA Repair Gene XRCC1 and Genetic Susceptibility to Lung Cancer in the Chinese Population

  • 摘要: 目的:DNA修复系统基因在维持基因组整体性及预防癌变过程中起着重要作用。碱基切除修复是DNA修复途径之一,主要切除DNA分子的小型损伤。XRCC1蛋白分子是碱基切除修复途径的重要组成成分。本研究探讨了DNA修复基因XRCC1 Pro206Pro与Gln632Gln单核苷酸多态与肺癌发生风险。方法:采用PCR-RFLP分型技术,分析中国东北地区汉族群体中247例肺癌患者与253例正常对照者的XRCC1 Pro206Pro和Gln632Gln多态/单体型与肺癌易感性及其与吸烟之间的关联。肺癌病例与正常对照者在年龄(±3岁)、性别及民族方面相配对。结果:XRCC1 Pro206Pro(G)变异等位基因携带者与AA野生等位基因纯合子个体相比较,有1.96倍高的肺癌发生风险(ad-justedOR=1.96,95%CI=1.26~3.06,P=0.003)(OR值经吸烟史校正)。对于XRCC1 Gln632Gln单一位点研究,未发现有统计学意义。分层分析未观察到基因型与吸烟史之间可能的基因与环境的相互作用。两个SNPs之间存在强烈的连锁不平衡(D'=0.807,P=3.1e-115),单体型在肺癌组与对照组之间的总体分布有极显著性差异(P=2.25e-06)。单体型2(Pro206Pro(A)-Gln632Gln(G)是抗风险性单体型(OR=0.66,95%CI=0.45~0.96,P=0.03),而单体型4(Pro206Pro(G)-Gln632Gln(G)是高风险性单体型(OR=16.09,95%CI=3.89~66.53,P=3.09e-07),这表明了基因与基因之间的相互作用对于复杂疾病研究的重要性。结论:XRCC1Pro206Pro等位基因及含其等位基因的单体型可能在肺癌的发生过程中起着重要作用。

     

    Abstract: Objective: DNA repair plays important roles in maintaining genomic integrity and prevention of carcinogenesis. Base excision repair (BER) is one type of DNA repair that operates on small lesions. XRCC1 (X-ray repair cross complementing group1) protein is an important component of BER. The aim of this study was to evaluate the association between the Pro206Pro and Gln632Gln polymorphisms of DNA repair gene XRCC1 and the prevalence of lung cancer in the Chinese population. Methods: A hospital-based case control study was designed that consisted of 247 cases of lung cancer and 253 cancer-free control subjects matched in age (± 3 years), gender and ethnicity. All subjects were ethnic Han Chinese and were unrelated. PCR-RFLP was used for genotyping. Results: Carriers of the variant G-allele of Pro206Pro were at significantly increased risk of developing lung cancer(adjusted OR=1.96, 95% CI=1.26-3.06, P=0.003, adjusted for smoking duration). No significant factors were associated with the Gln632Gln XRCC1 polymorphism. Interactions between genotype and smoking history were not seen in stratified analysis. The two SNPs were in strong linkage disequilibrium (D'=0.807, P= 3.1e-115). Haplotype distributions were significantly different between lung cancer cases and the controls(P=2.25e-06). A haplotype of Pro206Pro(A)-Gln632Gln(G) was associated with decreased risk of lung cancer(OR=0.66, 95% CI=0.45-0.96, P=0.03) and a haplotype of Pro206Pro(G)-Gln632Gln(G) was associated with significantly increased risk of lung cancer (OR=16.09, 95% CI=3.89-66.53, P=3.09e07). This finding indicates that the interaction between these genes is closely related to disease susceptibility. Conclusion: Polymorphisms in the DNA repair gene XRCC1 may play an important role in the occurrence of lung cancer in the Chinese population.

     

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