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A potentially functional polymorphism in the promoter region of miR-34b/c is associated with an increased risk for primary hepatocellular carcinoma.
MiR-34b/c 启动子区域的潜在功能多态性与原发性肝癌风险增加相关。

摘要

The miR-34 family members are direct transcriptional targets of tumor suppressor p53, and loss of miR-34 function can impair p53-mediated cell cycle arrest and apoptosis. A potentially functional SNP rs4938723 (T > C) was found in the promoter region of pri-miR-34b/c (423 bp from the transcription start site), located in the CpG island and might affect transcription factor GATA binding and therefore pri-miR-34b/c expression. In our study, we hypothesized that SNPs miR-34b/c rs4938723 and TP53 Arg72Pro may independently or jointly contribute to primary hepatocellular carcinoma (HCC) susceptibility. We then genotyped the 2 SNPs in a case-control study of 501 patients with primary HCC and 548 cancer-free controls in a Chinese population. We observed that the variant genotypes of miR-34b/c rs4938723 were associated with significantly increased HCC risks compared with the wild-type TT genotype (adjusted OR = 1.37, 95% CI =1.06-1.78 for TC; OR = 1.53, 95% CI = 1.02-2.31 for CC and OR = 1.40, 95% CI = 1.10-1.80 for TC/CC). Furthermore, we found a significant interaction between alcohol drinking and SNP rs4938723 on HCC risk (p = 0.05 for multiplicative and p = 0.01 for additive interaction). However, we did not find any main effect of TP53 Arg72Pro on HCC risk in this population. These findings indicate that the potentially functional SNP rs4938723 in the promoter region of pri-miR-34b/c may contribute to the susceptibility of HCC in this Chinese population.

译文

MiR-34 家族成员是肿瘤抑制基因 p53 的直接转录靶点,miR-34 功能的丧失会损害 p53-mediated 细胞周期阻滞和细胞凋亡。在 pri-miR-34b/C (转录起始位点 423 bp) 的启动子区域发现了一个潜在的功能性 SNP rs4938723 (T> c), 位于 CpG 岛,可能影响转录因子 GATA 结合,因此 pri-miR-34b/c 表达。在我们的研究中,我们假设 SNPs miR-34b/c rs4938723 和 TP53 Arg72Pro 可能独立或共同促进原发性肝癌 (HCC) 的易感性。然后,我们对 501 例原发性肝癌患者和 548 例中国人群中无癌症对照的病例对照研究中的 2 个 SNPs 进行了基因分型。我们观察到,与野生型 TT 基因型相比,miR-34b/c rs4938723 的变异基因型与显著增加的肝癌风险相关 (调整 OR = 1.37, TC 的 95% CI = 1.06-1.78; CC 的 OR = 1.53,95% CI = 1.02-2.31,TC/CC 的 OR = 1.40,95% CI = 1.10-1.80)。此外,我们发现饮酒和 SNP rs4938723 对肝癌风险之间有显著的相互作用 (p = 0.05 的乘法和 p = 0.01 的相加相互作用)。然而,我们没有发现 TP53 Arg72Pro 对该人群中肝癌风险的任何主要影响。这些发现表明,pri-miR-34b/c 启动子区的潜在功能 SNP rs4938723 可能有助于中国人群中肝癌的易感性。

primary hepatocellular carcinoma

消化 肝癌指征 疾病
概述  :  

原发性肝癌(primary carcinoma of the liver)是我国常见恶性肿瘤之一。死亡率高,在恶性肿瘤死亡顺位中仅次于胃、食道而居第三位,在部份地区的农村中则占第二位,仅次于胃癌。我国每年死于肝癌约11万人,占全世界肝癌死亡人数的45%。由于依靠血清甲胎蛋白(AFP)检测,结合超声显像对高危人群的监测,使肝癌在亚临床阶段即可给出诊断,早期切除的远期效果尤为显著。加之积极综合治疗,已使肝癌的五年生存率有了显著提高。   肝癌指

primary 英 /ˈpraɪməri/  美 /ˈpraɪmeri/

释义   adj. 主要的;初级的;基本的

n. 原色;最主要者

例句   The project has set "high quality" as one of its primary goals.  这个项目已经将“高质量”设定为它的主要目标之一。

 

hepatocellular /,hepətəʊ'seljʊlə/

释义   adj. 肝细胞的

例句   Expression of MT1E during the formation of hepatocellular carcinoma and its function in hepatocarcinoma cells.  MT1E在肝癌形成过程中的表达及其在肝癌细胞中的作用。

 

carcinoma 英 /ˌkɑːsɪˈnəʊmə/  美 /ˌkɑːrsɪˈnoʊmə/

释义   n. [肿瘤] 癌

例句   In rare cases, chronic erythema ab igne can lead to squamous cell carcinoma, a form of cancer. 在极少情况下,慢性红斑抗体可导致鳞状细胞癌,这是癌症的一种。

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