Associations between NBS1 Polymorphisms and Colorectal Cancer in Chinese Population.
Associations between NBS1 Polymorphisms and Colorectal Cancer in Chinese Population.
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NBS1多态性与中国人群结直肠癌的相关性
DOI：
10.1371/journal.pone.0132332
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Zhao HC
中科院分区：
文献类型：
--
作者：
Li JT;Zhong BY;Xu HH;Qiao SY;Wang G;Huang J;Fan HZ;Zhao HC
作为双链断裂（DSB）诱导的DNA修复通路的中心蛋白，NBS1参与DSB的检测，在维持基因组稳定性方面发挥重要作用。NBS1基因的单核苷酸多态性（SNPs）与多种癌症的易感性相关，但结果仍存在争议。因此，我们进行了两项独立的基于医院的病例对照研究，包括1,072名结直肠癌患者和1,263名对照，以评估4个NBS1 snp与结直肠癌风险之间的关系。结果显示，经logistic回归分析，NBS1 3′-非翻译区（UTR） rs2735383C/G多态性与结直肠癌发病风险显著相关（P<10-4）。此外，我们观察到，与rs2735383GC+GG基因型相比，rs2735383CC基因型与结直肠癌风险显著增加相关（优势比=1.55,95%置信区间= 1.27-1.94）。进一步的功能实验表明，在结直肠癌细胞中，NBS1中的rs2735383C等位基因破坏了has-miR-509-5p与NBS1 3 ' -UTR的结合亲和力，影响NBS1的转录活性和表达水平。总之，目前的证据表明rs2735383C/G多态性可能与结直肠癌的风险有关。
As the central protein of the double strand breaks (DSB)-induced DNA repair pathway, NBS1 participates in detecting the DSBs and plays an essential role in maintaining genomic stability. Single nucleotide polymorphisms (SNPs) in NBS1 gene were commonly tested that associated with the susceptibility to multiple cancers, but the results remained controversial. Thus, we conducted two independent hospital-based case–control studies comprising 1,072 colorectal cancer patients and 1,263 controls to evaluate the association between four NBS1 SNPs and colorectal cancer risk. The result showed that rs2735383C/G polymorphism in the 3’-untranslated region (UTR) of NBS1 was significantly associated with risk of colorectal cancer using logistic regression (P<10-4). Furthermore, we observed that rs2735383CC genotype was associated with substantially increased risk of colorectal cancer (odds ratio=1.55, 95% confidence interval=1.27–1.94), compared with the rs2735383GC+GG genotypes. Further functional experiments demonstrated that the rs2735383C allele in the NBS1 disrupted the binding affinity of has-miR-509-5p to the NBS1 3’-UTR in colorectal cancer cells, affecting the NBS1 transcriptional activity and expression level. In conclusion, current evidence suggests that the rs2735383C/G polymorphism might contribute to the risk for colorectal cancer.