Gamma-radiation sensitivity and polymorphisms in RAD51L1 modulate glioma risk
Gamma-radiation sensitivity and polymorphisms in RAD51L1 modulate glioma risk
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DOI：
10.1093/carcin/bgq141
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发表时间：
2010-10-01
期刊：
影响因子：
4.7
通讯作者：
Bondy, Melissa L.
中科院分区：
文献类型：
--
作者：
Liu, Yanhong;Shete, Sanjay;Bondy, Melissa L.
研究方法：我们在426例胶质瘤患者的样本中将DNA链断裂修复基因的标签单核苷酸多态性（tSNP）基因型数据与γ辐射诱导的诱变剂敏感性表型[表示为每个细胞的平均断裂（B/C）]相关联。我们还进行了分析，以评估单核苷酸多态性（SNP）对诱变剂敏感性的联合和单倍型效应。结果：在检测的392个tSNPs中，我们发现EME 2基因的1个tSNPs和RAD 51 L1基因的6个tSNPs对诱变剂敏感性有显著影响（P < 0.01）。在验证集中检测的6个RAD 51 L1 SNP中，1个（RAD 51 L1 rs 2180611）与诱变剂敏感性显著相关（P = 0.025）。此外，我们发现诱变剂敏感性与不良tSNP基因型数量之间存在显著的剂量-反应关系。此外，单倍型分析显示，RAD 51 L1单倍型F-A（0个不利等位基因）和F-E（6个不利等位基因）分别表现出最低（0.42）和最高（0.93）的平均B/C值。一个类似的剂量-反应关系也存在诱变剂的敏感性和不良haplotypes.Conclusion的数量之间：这些结果表明，多态性和单倍型的RAD 51 L1基因，这是参与双链断裂修复途径，调节γ辐射诱导的诱变剂敏感性。
Methods: We correlated genotype data for tag single-nucleotide polymorphisms (tSNPs) of DNA strand break repair genes with a gamma-radiation-induced mutagen sensitivity phenotype [expressed as mean breaks per cell (B/C)] in samples from 426 glioma patients. We also conducted analysis to assess joint and haplotype effects of single-nucleotide polymorphisms (SNPs) on mutagen sensitivity. We further validate our results in an independent external control group totaling 662 subjects.Results: Of the 392 tSNPs examined, we found that mutagen sensitivity was modified by one tSNP in the EME2 gene and six tSNPs in the RAD51L1 gene (P < 0.01). Among the six RAD51L1 SNPs tested in the validation set, one (RAD51L1 rs2180611) was significantly associated with mutagen sensitivity (P = 0.025). Moreover, we found a significant dose-response relationship between the mutagen sensitivity and the number of adverse tSNP genotypes. Furthermore, haplotype analysis revealed that RAD51L1 haplotypes F-A (zero adverse allele) and F-E (six adverse alleles) exhibited the lowest (0.42) and highest (0.93) mean B/C values, respectively. A similar dose-response relationship also existed between the mutagen sensitivity and the number of adverse haplotypes.Conclusion: These results suggest that polymorphisms in and haplotypes of the RAD51L1 gene, which is involved in the double-strand break repair pathway, modulate gamma-radiation-induced mutagen sensitivity.