本文選題：Epiregulin + DEC1��； 參考：《南京醫(yī)科大學》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胞癌(Esophageal squamous cell carcinoma,ESCC)或腺癌(Esophageal adenocarcinoma,EADC)。ESCC在中國發(fā)病率高,且預后不良。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)與瓣狀內切核酸酶 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方法測定EREG rs1460008 AG、DEC1 rs4978620 TC,rs2269700 TC,rs3750505 GA、FEN1 rs174538 GA的基因型。結果:當以EREGrs1460008 AA純合子基因型作為參照組時,GG基因型與ESCC的風險無關;AG基因型顯著降低ESCC的風險(AG vs.AA:調整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 風險無關。EREG rs1460008 AG SNP與ESCC的患病風險降低具有相關性;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:調整OR = 0.85,95%CI = 0.68-1.07,p = 0.176)都與ESCC風險相關沒有相關性。當使用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的風險無關(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 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)。結論:我們進行了一項基于食管癌病例和對照的研究,以評估EREG、DEC1和FEN1的SNPs之間的關聯(lián)以及食管癌的易感性。我們的研究結果表明,EREG rs1460008 AG SNP與ESCC的患病風險降低具有相關性,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特征來確認當前的發(fā)現。
[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.
【學位授予單位】：南京醫(yī)科大學
【學位級別】：博士
【學位授予年份】：2017
【分類號】：R735.1

【參考文獻】

相關期刊論文 前10條

1 秦豐;史學森;;食管癌早期診斷研究進展[J];包頭醫(yī)學院學報;2012年05期

2 周衡;黃貴華;;中醫(yī)對食管癌的認識和治療研究進展[J];遼寧中醫(yī)藥大學學報;2012年02期

3 杜萍;丁黎葭;馬麗黎;陳世耀;練晶晶;邱楓;吳永梅;毛於安;姚禮慶;;應用內鏡黏膜下剝離術處理食管黏膜病變療效評價[J];生物醫(yī)學工程與臨床;2012年01期

4 王文憑;陳龍奇;;食管癌外科治療的現狀與展望[J];中國胸心血管外科臨床雜志;2011年01期

5 ;Inhibitory effects of miRNA-200c on chemotherapy-resistance and cell proliferation of gastric cancer SGC7901/DDP cells[J];癌癥;2010年12期

6 王敏;鄭燕;郟雁飛;李彬彬;汪運山;;轉錄調節(jié)因子DEC1的研究進展[J];山東科學;2008年04期

7 高繼良;沈壯虹;;滌痰化瘀法治療中晚期食道癌30例[J];浙江中醫(yī)藥大學學報;2007年02期

8 崔永玲;;金龍膠囊結合中藥辨證治療食管癌60例療效觀察[J];北京中醫(yī);2006年06期

9 梁震,孫貞媛,袁艷華,韓燕,王kH,顧晉,張力建;11種癌-睪丸抗原基因在食管癌中表達的檢測[J];中華腫瘤雜志;2005年09期

10 彭仙娥,史習舜;食管癌病因學研究進展[J];腫瘤防治雜志;2003年09期

，

本文編號：1954084