Lin Zhong-Hui, Chen Jin-Chun, Wang Yun-Sun, Huang Teng-Jiao, Wang Jin, Long Xi-Dai
Department of Neurology Medicine, Xia-Men Hospital of Traditional Chinese Medicine, Xiamen 361009, China.
Int J Mol Sci. 2013 Dec 27;15(1):250-60. doi: 10.3390/ijms15010250.
The DNA repair gene X-ray cross-complementary group 4 (XRCC4), an important caretaker of the overall genome stability, is thought to play a major role in human tumorigenesis. We investigated the association between an important polymorphic variant of this gene at codon 247 (rs373409) and diffusely infiltrating astrocytoma (DIA) risk and prognosis. This hospital-based case-control study investigated this association in the Guangxi population. In total, 242 cases with DIA and 358 age-, sex-, and race-matched healthy controls were genotyped using TaqMan-PCR technique. We found a significant difference in the frequency of XRCC4 genotypes between cases and controls. Compared with the homozygote of XRCC4 codon 247 Ala alleles (XRCC4-AA), the genotypes of XRCC4 codon 247 Ser alleles (namely XRCC4-AS or -SS) increased DIA risk (odds ratios [OR], 1.82 and 2.89, respectively). Furthermore, XRCC4 polymorphism was correlated with tumor dedifferentiation of DIA (r = 0.261, p < 0.01). Additionally, this polymorphism modified the overall survival of DIA patients (the median survival times were 26, 14, and 8 months for patients with XRCC4-AA, -AS, and -SS, respectively). Like tumor grade, XRCC4 codon 247 polymorphism was an independent prognostic factor influencing the survival of DIA. These results suggest that XRCC4 codon 247 polymorphism may be associated with DIA risk and prognosis among the Guangxi population.
DNA修复基因X射线交叉互补组4（XRCC4）是整个基因组稳定性的重要守护者，被认为在人类肿瘤发生中起主要作用。我们研究了该基因第247密码子处一个重要的多态性变体（rs373409）与弥漫性浸润性星形细胞瘤（DIA）风险及预后之间的关联。这项基于医院的病例对照研究在广西人群中调查了这种关联。总共使用TaqMan-PCR技术对242例DIA患者和358名年龄、性别及种族匹配的健康对照进行了基因分型。我们发现病例组和对照组之间XRCC4基因型频率存在显著差异。与XRCC4第247密码子丙氨酸等位基因的纯合子（XRCC4-AA）相比，XRCC4第247密码子丝氨酸等位基因的基因型（即XRCC4-AS或-SS）增加了DIA风险（优势比[OR]分别为1.82和2.89）。此外，XRCC4多态性与DIA的肿瘤去分化相关（r = 0.261，p < 0.01）。此外，这种多态性改变了DIA患者的总生存期（XRCC4-AA、-AS和-SS患者的中位生存期分别为26、14和8个月）。与肿瘤分级一样，XRCC4第247密码子多态性是影响DIA患者生存的独立预后因素。这些结果表明，XRCC4第247密码子多态性可能与广西人群的DIA风险及预后相关。
