Significance of genetic variants in DLC1 and their association with hepatocellular carcinoma.
Significance of genetic variants in DLC1 and their association with hepatocellular carcinoma.
复制标题
DLC1基因变异的意义及其与肝细胞癌的关系
DOI：
10.3892/mmr.2015.3970
复制
发表时间：
2015-09
影响因子：
3.4
通讯作者：
Yin ZY
中科院分区：
文献类型：
--
作者：
Xie CR;Sun HG;Sun Y;Zhao WX;Zhang S;Wang XM;Yin ZY
DLC1 已被证明在肝细胞癌 (HCC) 中下调或缺失，并且与肿瘤发生和发展相关。然而，只有少数研究关注 DLC1 的遗传变异。本研究对 105 名患者的 HCC 组织样本中的 DLC1 基因进行了外显子测序，以鉴定 DLC1 的功能遗传变异及其与 HCC 易感性、临床病理特征和预后的关系。鉴定出一种新的错义突变和四个非同义单核苷酸多态性（SNP；rs3816748、rs11203495、rs3816747 和 rs532841）。 rs3816747 多态性与 HCC 易感性存在显着相关性。与具有 rs3816747 GG 基因型的个体相比，具有 GA（比值比 (OR)=0.486；P=0.037）或 GA+AA 基因型（OR=0.51；P=0.039）的个体与 HCC 风险显着降低相关。此外，与携带野生型基因型的患者相比，具有rs3816748的GC+CC基因型、rs11203495的TC+CC基因型或rs3816747的GA+AA基因型的患者的肿瘤尺寸较小。未发现 DLC1 SNP 与患者预后存在显着关联。这些结果表明 DLC1 基因的遗传变异可能会增加患 HCC 的风险。
DLC1 has been shown to be downregulated or absent in hepatocellular carcinoma (HCC) and is associated with tumorigenesis and development. However, only a small number of studies have focused on genetic variations of DLC1. The present study performed exon sequencing for the DLC1 gene in HCC tissue samples from 105 patients to identify functional genetic variation of DLC1 and its association with HCC susceptibility, clinicopathological features and prognosis. A novel missense mutation and four non-synonymous single nucleotide polymorphisms (SNPs; rs3816748, rs11203495, rs3816747 and rs532841) were identified. A significant correlation of rs3816747 polymorphisms with HCC susceptibility was identified. Compared to individuals with the GG genotype of rs3816747, those with the GA (odds ratio (OR)=0.486; P=0.037) or GA+AA genotype (OR=0.51; P=0.039) were associated with a significantly decreased HCC risk. Furthermore, patients with the GC+CC genotype of rs3816748, the TC+CC genotype of rs11203495 or the GA+AA genotype of rs3816747 had small-sized tumors compared with those carrying the wild-type genotype. No significant association of DLC1 SNPs with the patients' prognosis was found. These results indicated that genetic variations in the DLC1 gene may confer a risk for HCC.