Zhao Xiaodong, Wang Tianyi, Liu Bo, Wu Zhenzhou, Yu Shuo, Wang Tao
Department of Oncological Surgery, The Second Hospital of Hebei Medical University, 215 Peace West Road, Shijiazhuang, 050000, China.
Tumour Biol. 2015 Apr;36(4):2551-8. doi: 10.1007/s13277-014-2871-3. Epub 2014 Dec 6.
Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide with high mortality rate. Upstream transcription factor 1 (USF1) is a ubiquitously expressed transcription factor that regulates the expression of genes involving in different biological processes, including cancer. The aim of this study is to examine the correlation between USF1 polymorphisms and HCC susceptibility. Ninety-four HCC patients and 100 healthy volunteers are recruited in our study. Tag single nucleotide polymorphisms (Tag-SNPs) were retrieved in the International HapMap Project Databases. Extraction of genomic DNAs was conducted with TaqMan Blood DNA kits. Genotyping of USF1 polymorphisms were carried out with TaqMan SNPs genotyping assay. Odds ratios (ORs) and their 95% confidence intervals (CIs) were calculated to evaluate the association between USF1 polymorphisms and HCC risk. All statistical analyses were performed with SPSS 20.0 software. Five tag-SNPs were identified to represent the genetic variants of USF1. Our results suggested that rs2516839 in the 5'UTR of USF1 was significantly associated with increased HCC risk (AA vs GG: OR = 3.15; 95% CI 1.44-6.87; P = 0.003; GA + AA vs AA: OR = 1.85; 95% CI 1.04-3.30; P = 0.034; AA vs GG + GA: OR = 2.96; 95% CI 1.40-6.26; P = 0.004; A vs G: OR = 2.09; 9% CI 1.35-3.23; P < 0.001). Although rs2073655 in the intron region of USF1 was also shown to be correlated with decreased HCC susceptibility in recessive model (TT vs CC + CT: OR = 0.40; 95% CI 0.54-0.75; P = 0.004), this association was not conclusive. Our results indicated that the SNP of rs2516839 have close association with increased risk of HCC. Further studies may be needed to validate our results and gain insights into the pathological mechanism of USF1 gene in the HCC tumorigenesis.
肝细胞癌(HCC)是全球最常见的癌症之一,死亡率很高。上游转录因子1(USF1)是一种广泛表达的转录因子,可调节涉及不同生物学过程(包括癌症)的基因表达。本研究的目的是探讨USF1基因多态性与HCC易感性之间的相关性。我们的研究招募了94例HCC患者和100名健康志愿者。在国际HapMap项目数据库中检索标签单核苷酸多态性(Tag-SNPs)。使用TaqMan Blood DNA试剂盒提取基因组DNA。采用TaqMan SNPs基因分型检测法对USF1基因多态性进行基因分型。计算优势比(OR)及其95%置信区间(CIs),以评估USF1基因多态性与HCC风险之间的关联。所有统计分析均使用SPSS 20.0软件进行。鉴定出5个Tag-SNPs代表USF1的遗传变异。我们的结果表明,USF1基因5'UTR中的rs2516839与HCC风险增加显著相关(AA与GG比较:OR = 3.15;95% CI 1.44 - 6.87;P = 0.003;GA + AA与AA比较:OR = 1.85;95% CI 1.04 - 3.30;P = 0.034;AA与GG + GA比较:OR = 2.96;95% CI 1.40 - 6.26;P = 0.004;A与G比较:OR = 2.09;9% CI 1.35 - 3.23;P < 0.001)。尽管USF1基因内含子区域的rs2073655在隐性模型中也显示与HCC易感性降低相关(TT与CC + CT比较:OR = 0.40;95% CI 0.54 - 0.75;P = 0.004),但这种关联并不确定。我们的结果表明,rs2516839的SNP与HCC风险增加密切相关。可能需要进一步的研究来验证我们的结果,并深入了解USF1基因在HCC肿瘤发生中的病理机制。