A RAD52 genetic variant located in a miRNA binding site is associated with glioma risk in Han Chinese
A RAD52 genetic variant located in a miRNA binding site is associated with glioma risk in Han Chinese
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DOI：
10.1007/s11060-014-1527-x
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发表时间：
2014-07
影响因子：
3.9
通讯作者：
Chao Lu;Yidong Chen;Sichong Han;Jinyu Wei;Yunxia Ge;Wenting Pan;T. Jiang;Xiaoguang Qiu;Ming Yang
中科院分区：
文献类型：
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作者：
Chao Lu;Yidong Chen;Sichong Han;Jinyu Wei;Yunxia Ge;Wenting Pan;T. Jiang;Xiaoguang Qiu;Ming Yang
RAD 52作为一个重要的同源重组修复基因，参与维持基因组的稳定性和预防肿瘤的发生。尽管以前已经发现了几种癌症易感性的RAD 52单核苷酸多态性（single nucleotide polymorphisms，SNPs），但对RAD 52 SNPs如何参与中国汉族人胶质瘤的发生知之甚少。因此，我们使用病例对照设计研究了5个RAD 52 SNPs（rs 1051669，rs 10774474，rs 11571378，rs7963551和rs6489769）与胶质瘤风险之间的关联。用逻辑回归估计比值比（OR）和95%置信区间（CI）。我们发现只有RAD 52 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基因型的几率为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）。这些数据与癌细胞中rs7963551 SNP和miRNA let-7对RAD 52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之间的统计学显著相关性仅存在于星形细胞肿瘤（P= 6.3 × 10−6）或寡星形细胞肿瘤（P= 0.002）中。总之，我们的研究结果支持这样的假设，即影响肿瘤抑制基因或癌基因的miRNA介导的调节的遗传变异可能有助于胶质瘤的易感性。
As a crucial homologous recombination repair gene, RAD52 participates in maintenance of genomic stability and prevention of tumorigenesis. Although several cancer susceptibilityRAD52single nucleotide polymorphisms (SNPs) have been identified previously, little was known on how theRAD52SNPs are involved in glioma development in Han Chinese. Therefore, we examined the association between fiveRAD52SNPs (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 theRAD52rs7963551 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.