Custódio A C, Almeida L O, Pinto G R, Santos M J, Almeida J R W, Clara C A, Rey J A, Casartelli C
Laboratório de Oncogenética, Departamento de Genética, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP, Brasil.
Genet Mol Res. 2011 Jun 14;10(2):1120-9. doi: 10.4238/vol10-2gmr1125.
XRCC genes (X-ray cross-complementing group) were discovered mainly for their roles in protecting mammalian cells against damage caused by ionizing radiation. Studies determined that these genes are important in the genetic stability of DNA. Although the loss of some of these genes does not necessarily confer high levels of sensitivity to radiation, they have been found to represent important components of various pathways of DNA repair. To ensure the integrity of the genome, a complex system of DNA repair was developed. Base excision repair is the first defense mechanism of cells against DNA damage and a major event in preventing mutagenesis. Repair genes may play an important role in maintaining genomic stability through different pathways that are mediated by base excision. In the present study, we examined XRCC1Arg194Trp and XRCC1Arg399Gln polymorphism using PCR-RFLP in 80 astrocytoma and glioblastoma samples. Patients who had the allele Trp of the XRCC1Arg194Trp polymorphism had an increased risk of tumor development (OR = 8.80; confidence interval at 95% (95%CI) = 4.37-17.70; P < 0.001), as did the allele Gln of XRCC1Arg399Gln (OR = 1.01; 95%CI = 0.53-1.93; P = 0.971). Comparison of overall survival of patients did not show significant differences. We suggest that XRCC1Arg194Trp and XRCC1Arg399Gln polymorphisms are involved in susceptibility for developing astrocytomas and glioblastomas.
XRCC基因（X射线交叉互补组）主要因其在保护哺乳动物细胞免受电离辐射损伤方面的作用而被发现。研究确定这些基因在DNA的遗传稳定性中很重要。虽然其中一些基因的缺失不一定会导致对辐射的高度敏感性，但已发现它们代表DNA修复各种途径的重要组成部分。为确保基因组的完整性，已形成了一个复杂的DNA修复系统。碱基切除修复是细胞抵御DNA损伤的第一道防线，也是预防诱变的一个主要事件。修复基因可能通过碱基切除介导的不同途径在维持基因组稳定性方面发挥重要作用。在本研究中，我们使用聚合酶链反应-限制性片段长度多态性（PCR-RFLP）检测了80例星形细胞瘤和胶质母细胞瘤样本中的XRCC1Arg194Trp和XRCC1Arg399Gln多态性。具有XRCC1Arg194Trp多态性Trp等位基因的患者发生肿瘤的风险增加（比值比（OR）= 8.80；95%置信区间（95%CI）= 4.37 - 17.70；P < 0.001），XRCC1Arg399Gln的Gln等位基因患者也是如此（OR = 1.01；95%CI = 0.53 - 1.93；P = 0.971）。患者总体生存率的比较未显示出显著差异。我们认为XRCC1Arg194Trp和XRCC1Arg399Gln多态性与星形细胞瘤和胶质母细胞瘤的易感性有关。
