本文選題：Epiregulin + DEC1�。� 參考：《南京醫(yī)科大學(xué)》2017年博士論文

【摘要】：目的:食管癌是一種全球死亡率非常高的腫瘤疾病,特別是在亞洲,食管癌是2009年排在中國公開診斷的癌癥種類的第五位,中國第四大癌癥相關(guān)死亡的腫瘤。其發(fā)病率顯示明顯的種族差異。食管癌可分為鱗狀細(xì)胞癌(Esophageal squamous cell carcinoma,ESCC)或腺癌(Esophageal adenocarcinoma,EADC)。ESCC在中國發(fā)病率高,且預(yù)后不良。然而,ESCC的發(fā)病受遺傳和環(huán)境因素之間相互作用的影響。因此我們嘗試探索ESCC與遺傳因素之間的潛在聯(lián)系。方法:本研究旨在評估與表皮調(diào)節(jié)素(Epiregulin,EREG)、分化型胚胎軟骨發(fā)育基因 1(Differentiated embryo-chondrocyte expressed genel,DEC1)與瓣?duì)顑?nèi)切核酸酶 1(Flap endonuclease-1,FEN1)中功能性單核苷酸多態(tài)性(Single Nucleotide Polymorphisms,SNP)相關(guān)的ESCC的遺傳易感性。我們從629例ESCC患者和686例對照受試者收集血液樣品,并使用連接檢測反應(yīng)方法測定EREG rs1460008 AG、DEC1 rs4978620 TC,rs2269700 TC,rs3750505 GA、FEN1 rs174538 GA的基因型。結(jié)果:當(dāng)以EREGrs1460008 AA純合子基因型作為參照組時,GG基因型與ESCC的風(fēng)險無關(guān);AG基因型顯著降低ESCC的風(fēng)險(AG vs.AA:調(diào)整OR為0.76,95%CI為0.60-0.96,P = 0.020)。Logistic回歸分析顯示,在所有比較模型中,DEC1 rs4978620 TC,rs2269700 TC 和 rs3750505 GA 多態(tài)性與 ESCC 風(fēng)險無關(guān)。EREG rs1460008 AG SNP與ESCC的患病風(fēng)險降低具有相關(guān)性;在使用FEN1 rs174538GG/AA基因型作為參照組的隱性模型中,無論是AA純合子基因型(AA對GG/AA:調(diào)整OR=1.18,95%CI=0.83-1.68,p=0.355),或者GA/AA純合子基因型(GA/AA對GG/AA:調(diào)整OR = 0.85,95%CI = 0.68-1.07,p = 0.176)都與ESCC風(fēng)險相關(guān)沒有相關(guān)性。當(dāng)使用FEN1 rs174538 GG純合子基因型作為參考組時,GA基因型,AA基因型均與ESCC的風(fēng)險無關(guān)(GA與GG:adjusted OR = 0.81,95%CI = 0.64-1.04,p = 0.092),(AA與GG:adjusted OR = 1.05,95%CI = 0.72-1.53,p = 0.802)。當(dāng) FEN1rs174538 GG 基因型用作參照組時,FEN1 rs174538 GA基因型在63歲以下人群,ESCC的患病風(fēng)險顯著降低(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歲以下人群,ESCC的患病風(fēng)險顯著降低(GA/AA vs.GG:OR = 0.70,95%CI = 0.50-0.97,p = 0.034,ph = 0.045)。結(jié)論:我們進(jìn)行了一項(xiàng)基于食管癌病例和對照的研究,以評估EREG、DEC1和FEN1的SNPs之間的關(guān)聯(lián)以及食管癌的易感性。我們的研究結(jié)果表明,EREG rs1460008 AG SNP與ESCC的患病風(fēng)險降低具有相關(guān)性,EREG rs1460008 AG可能是食管癌的潛在功能性SNP。FEN1 rs174538 GA中的功能多態(tài)性可能影響63歲以下個體對ESCC的易感性。此外,需要更多樣本支持的研究和組織特異性生物學(xué)特征來確認(rèn)當(dāng)前的發(fā)現(xiàn)。
[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.
【學(xué)位授予單位】：南京醫(yī)科大學(xué)
【學(xué)位級別】：博士
【學(xué)位授予年份】：2017
【分類號】：R735.1

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