Lu Chao, Chen Yi-Dong, Han Sichong, Wei Jinyu, Ge Yunxia, Pan Wenting, Jiang Tao, Qiu Xiao-Guang, Yang Ming
State Key Laboratory of Chemical Resource Engineering, College of Life Science and Technology, Beijing University of Chemical Technology, P. O. Box 53, Beijing, 100029, China.
J Neurooncol. 2014 Oct;120(1):11-7. doi: 10.1007/s11060-014-1527-x. Epub 2014 Jul 11.
As a crucial homologous recombination repair gene, RAD52 participates in maintenance of genomic stability and prevention of tumorigenesis. Although several cancer susceptibility RAD52 single nucleotide polymorphisms (SNPs) have been identified previously, little was known on how the RAD52 SNPs are involved in glioma development in Han Chinese. Therefore, we examined the association between five RAD52 SNPs (rs1051669, rs10774474, rs11571378, rs7963551 and rs6489769) and glioma risk using a case-control design. Odds ratios (ORs) and 95 % confidence intervals (CIs) were estimated by logistic regression. We found that only the RAD52 rs7963551 SNP was significantly associated with glioma risk, with the odds of having the rs7963551 AC or CC genotype in patients was 0.49 (95 % CI 0.37-0.65, P = 9.2 × 10(-6)) or 0.39 (95 % CI 0.18-0.81, P = 0.012) compared with the AA genotype. These data are consistent with functional relevance of allelic regulation of RAD52 expression by the rs7963551 SNP and miRNA let-7 in cancer cells. Stratified analyses elucidated that statistically significant association between glioma and rs7963551 SNP only existed in either astrocytic tumors (P = 6.3 × 10(-6)) or oligoastrocytic tumors (P = 0.002). In conclusion, our results support the hypothesis that genetic variants influencing miRNA-mediated regulation of tumor suppressor genes or oncogenes may contribute glioma susceptibility.
作为一个关键的同源重组修复基因，RAD52参与基因组稳定性的维持和肿瘤发生的预防。尽管之前已经鉴定出了几种与癌症易感性相关的RAD52单核苷酸多态性（SNP），但对于汉族人群中RAD52 SNP如何参与胶质瘤发生发展知之甚少。因此，我们采用病例对照设计研究了5个RAD52 SNP（rs1051669、rs10774474、rs11571378、rs7963551和rs6489769）与胶质瘤风险之间的关联。通过逻辑回归估计比值比（OR）和95%置信区间（CI）。我们发现只有RAD52 rs7963551 SNP与胶质瘤风险显著相关，与AA基因型相比，患者中rs7963551 AC或CC基因型的比值分别为0.49（95%CI 0.37 - 0.65，P = 9.2×10⁻⁶）或0.39（95%CI 0.18 - 0.81，P = 0.012）。这些数据与rs7963551 SNP和miRNA let - 7在癌细胞中对RAD52表达的等位基因调控的功能相关性一致。分层分析表明，胶质瘤与rs7963551 SNP之间的统计学显著关联仅存在于星形细胞瘤（P = 6.3×10⁻⁶）或少突星形细胞瘤（P = 0.002）中。总之，我们的结果支持这样的假设，即影响miRNA介导的肿瘤抑制基因或癌基因调控的遗传变异可能导致胶质瘤易感性。
