EREG,DEC1,FEN1基因多态性与食管癌易感性的相关研究

发布时间：2018-05-30 05:22

本文选题：Epiregulin + DEC1　；参考：《南京医科大学》2017年博士论文

【摘要】：目的:食管癌是一种全球死亡率非常高的肿瘤疾病,特别是在亚洲,食管癌是2009年排在中国公开诊断的癌症种类的第五位,中国第四大癌症相关死亡的肿瘤。其发病率显示明显的种族差异。食管癌可分为鳞状细胞癌(Esophageal squamous cell carcinoma,ESCC)或腺癌(Esophageal adenocarcinoma,EADC)。ESCC在中国发病率高,且预后不良。然而,ESCC的发病受遗传和环境因素之间相互作用的影响。因此我们尝试探索ESCC与遗传因素之间的潜在联系。方法:本研究旨在评估与表皮调节素(Epiregulin,EREG)、分化型胚胎软骨发育基因 1(Differentiated embryo-chondrocyte expressed genel,DEC1)与瓣状内切核酸酶 1(Flap endonuclease-1,FEN1)中功能性单核苷酸多态性(Single Nucleotide Polymorphisms,SNP)相关的ESCC的遗传易感性。我们从629例ESCC患者和686例对照受试者收集血液样品,并使用连接检测反应方法测定EREG rs1460008 AG、DEC1 rs4978620 TC,rs2269700 TC,rs3750505 GA、FEN1 rs174538 GA的基因型。结果:当以EREGrs1460008 AA纯合子基因型作为参照组时,GG基因型与ESCC的风险无关;AG基因型显著降低ESCC的风险(AG vs.AA:调整OR为0.76,95%CI为0.60-0.96,P = 0.020)。Logistic回归分析显示,在所有比较模型中,DEC1 rs4978620 TC,rs2269700 TC 和 rs3750505 GA 多态性与 ESCC 风险无关。EREG rs1460008 AG SNP与ESCC的患病风险降低具有相关性;在使用FEN1 rs174538GG/AA基因型作为参照组的隐性模型中,无论是AA纯合子基因型(AA对GG/AA:调整OR=1.18,95%CI=0.83-1.68,p=0.355),或者GA/AA纯合子基因型(GA/AA对GG/AA:调整OR = 0.85,95%CI = 0.68-1.07,p = 0.176)都与ESCC风险相关没有相关性。当使用FEN1 rs174538 GG纯合子基因型作为参考组时,GA基因型,AA基因型均与ESCC的风险无关(GA与GG:adjusted OR = 0.81,95%CI = 0.64-1.04,p = 0.092),(AA与GG:adjusted OR = 1.05,95%CI = 0.72-1.53,p = 0.802)。当 FEN1rs174538 GG 基因型用作参照组时,FEN1 rs174538 GA基因型在63岁以下人群,ESCC的患病风险显著降低(GA vs GG:adjusted OR = 0.63,95%CI = 0.45-0.90,p = 0.010,ph = 0.027),FEN1 rs174538 GA/AA基因型在63岁以下人群,ESCC的患病风险显著降低(GA/AA vs.GG:OR = 0.70,95%CI = 0.50-0.97,p = 0.034,ph = 0.045)。结论:我们进行了一项基于食管癌病例和对照的研究,以评估EREG、DEC1和FEN1的SNPs之间的关联以及食管癌的易感性。我们的研究结果表明,EREG rs1460008 AG SNP与ESCC的患病风险降低具有相关性,EREG rs1460008 AG可能是食管癌的潜在功能性SNP。FEN1 rs174538 GA中的功能多态性可能影响63岁以下个体对ESCC的易感性。此外,需要更多样本支持的研究和组织特异性生物学特征来确认当前的发现。
[Abstract]:Objective: esophageal cancer is a very high global mortality rate, especially in Asia. Esophageal cancer is the fifth most publicly diagnosed cancer in China in 2009, and the fourth major cancer related cancer in China. Its incidence shows a distinct racial difference. Cancer of the esophagus can be divided into Esophageal squamous cell CA Rcinoma, ESCC) or Esophageal adenocarcinoma (EADC).ESCC has high incidence and poor prognosis in China. However, the pathogenesis of ESCC is affected by the interaction between genetic and environmental factors. Therefore, we try to explore the potential link between ESCC and genetic factors. Methods: This study aims to evaluate the relationship between the epidermal regulator and the epidermal regulator (Epiregulin, EREG). The genetic susceptibility to functional single nucleotide polymorphisms (Single Nucleotide Polymorphisms, SNP) in the differentiated embryo cartilage development gene 1 (Differentiated Embryo-Chondrocyte Expressed Genel, DEC1) and the valve endonuclease 1 (Flap endonuclease-1, FEN1). We collected from 629 patients and 686 control subjects. Blood samples were collected and the genotype of EREG rs1460008 AG, DEC1 rs4978620 TC, rs2269700 TC, rs3750505 GA, FEN1 rs174538 were measured. R is 0.76,95%CI 0.60-0.96, P = 0.020).Logistic regression analysis shows that in all comparison models, DEC1 rs4978620 TC, rs2269700 TC and rs3750505 GA polymorphisms are related to the risk reduction of the risk. In the type of AA homozygote genotypes (AA versus GG/AA: OR=1.18,95%CI=0.83-1.68, p=0.355), or GA/AA homozygous genotypes (GA/AA versus GG/AA: to OR = 0.85,95%CI = 0.68-1.07, P = 0.176) are not related to the risk correlation. Not related to the risk of ESCC (GA and GG:adjusted OR = 0.81,95%CI = 0.64-1.04, P = 0.092), (AA and GG:adjusted OR = 1.05,95%CI = 0.72-1.53, = 0.802). = 0.45-0.90, P = 0.010, pH = 0.027), the FEN1 rs174538 GA/AA genotype in people under 63 years of age, the risk of ESCC is significantly reduced (GA/AA vs.GG:OR = 0.70,95%CI = 0.50-0.97, P = 0.034, 0.045). The susceptibility of esophageal cancer. Our findings suggest that EREG rs1460008 AG SNP is associated with a decrease in the risk of ESCC, and EREG rs1460008 AG may be a potential functional SNP.FEN1 rs174538 GA of the esophageal cancer, which may affect the susceptibility of individuals under 63 years of age to ESCC. In addition, more sample support is needed. And tissue specific biological characteristics to confirm the current findings.
【学位授予单位】：南京医科大学
【学位级别】：博士
【学位授予年份】：2017
【分类号】：R735.1

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