本文選題：乙肝相關(guān)性肝癌　切入點(diǎn)：白細(xì)胞介素-2　出處：《大連醫(yī)科大學(xué)》2017年碩士論文　論文類型：學(xué)位論文

【摘要】：背景及目的乙型肝炎病毒(HBV)相關(guān)性肝細(xì)胞癌(HCC)是一個(gè)復(fù)雜的、由多種基因及環(huán)境因素參與的多步驟過程。在中國(guó),約有90%的肝癌患者合并有HBV感染的背景。肝癌的發(fā)生與炎癥、免疫等多種因素相關(guān),HBV感染后,病毒長(zhǎng)期復(fù)制活動(dòng)引起肝臟慢性炎癥,刺激血管的再生、損傷DNA、刺激惡性腫瘤細(xì)胞的生長(zhǎng)等導(dǎo)致腫瘤發(fā)生,但具體的機(jī)制尚不清楚。單核苷酸多態(tài)性(SNP)是影響個(gè)體遺傳易感性的重要因素。目前有關(guān)白細(xì)胞介素-2(IL-2)SNP和白細(xì)胞介素-10(IL-10)SNP對(duì)HBV相關(guān)性HCC發(fā)病風(fēng)險(xiǎn)的相關(guān)性的研究觀點(diǎn)不一。本研究選取IL-2基因rs2069763位點(diǎn)及IL-10基因rs1800872位點(diǎn),探究這2個(gè)位點(diǎn)與HBV相關(guān)性HCC遺傳易感性的關(guān)系,并進(jìn)一步探討兩基因位點(diǎn)之間是否存在交互作用。方法本研究自2014年11月至2016年8月期間,于青島市市立醫(yī)院選取HBV相關(guān)性HCC的患者263例(男性216例)作為病例組,健康者350例(男性284例)作為對(duì)照組。收集受試者的血液標(biāo)本,通過多聚酶鏈反應(yīng)(PCR)及飛行時(shí)間質(zhì)譜方法(MALDI-TOF MS)檢測(cè)IL-2rs2069763、IL-10 rs1800872的基因型。同時(shí)收集受試者的一般資料、臨床資料及實(shí)驗(yàn)室檢查指標(biāo),利用SPSS 19.0統(tǒng)計(jì)軟件,用Pearson χ2檢驗(yàn)、t檢驗(yàn)及Logistic回歸分析等方法對(duì)各組基因型、基因位點(diǎn)及臨床資料等進(jìn)行分析。用廣義多因子降維軟件(GMDR)測(cè)IL-2基因SNP rs2069763位點(diǎn)和IL-10基因SNP rs1800872之間的交互作用。結(jié)果HBV相關(guān)性HCC組與對(duì)照組相比,在性別、年齡、飲酒史、吸煙史方面的差異無統(tǒng)計(jì)學(xué)意義(P0.05)。病例組血清總蛋白和白蛋白指標(biāo)明顯低于對(duì)照組(P0.01),而血清總膽紅素、直接膽紅素、間接膽紅素、谷丙轉(zhuǎn)氨酶、谷草轉(zhuǎn)氨酶(AST)、堿性磷酸酶(ALP)及谷氨酰轉(zhuǎn)肽酶(GGT)水平明顯高于健康對(duì)照組(P0.01)。IL-2基因rs2060763位點(diǎn)、IL-10基因rs1800872位點(diǎn)的基因型和等位基因的頻率分布在病例組和對(duì)照組之間的差異具有統(tǒng)計(jì)學(xué)意義(P值均0.05)。Rs2069763G等位基因和rs1800872G等位基因可以明顯增加HBV相關(guān)性 HCC 的發(fā)病風(fēng)險(xiǎn)(分別為:OR,1.541,95%CI,1.053 to 2.256,P=0.026,OR,1.402,95%CI,1.011 to 1.943,P=0.043)。在調(diào)整了混雜因素年齡、性別、飲酒及吸煙后,logistics回歸顯示這種差異依然具有統(tǒng)計(jì)學(xué)意義(分別為OR,1.605,95%CI,1.090 to 2.364,P=0.005;OR,1.465,0.579,95%CI,1.052 to 2.041,P=0.006)。在HBV相關(guān)性HCC組中,與非攜帶者相比,IL-2基因rs2069763位點(diǎn)G等位基因攜帶者具有更高的AST水平(P = 0.001)和更高的ALP水平(P0.001);IL-10基因中rs1800872的G等位基因攜帶者的ALT(P = 0.020)、AST(P = 0.011)和ALP(P = 0.024)的水平更高.GMDR軟件測(cè)交互性作用分析顯示IL-2基因rs2069763和IL-10基因rs1800872兩個(gè)位點(diǎn)之間無交互作用(P0.05),提示兩位點(diǎn)聯(lián)合作用時(shí)并不能對(duì)HBC相關(guān)性HCC的發(fā)病風(fēng)險(xiǎn)產(chǎn)生影響。結(jié)論在中國(guó)青島地區(qū)漢族人群中,IL-2rs2069763G等位基因及IL-10rs1800872 G等位基因可以增加HBV相關(guān)性HCC的發(fā)病風(fēng)險(xiǎn)。IL-2基因rs2069763位點(diǎn)及IL-10基因rs1800872位點(diǎn)之間對(duì)HBV相關(guān)性HCC易患性的影響無交互作用。
[Abstract]:Background and objective: hepatitis B virus (HBV) related hepatocellular carcinoma (HCC) is a complex, multi-step process involved by multiple genetic and environmental factors. In Chinese, about 90% of patients with primary hepatocellular carcinoma with HBV infection and inflammation of liver cancer. The background, immune and other factors related to HBV infection. After long-term virus replication activity caused by chronic liver inflammation, regeneration, stimulation of vascular injury DNA, stimulation of malignant tumor cell growth and tumorigenesis, but the mechanism is not clear. The single nucleotide polymorphism (SNP) is an important factor affecting the individual genetic susceptibility. The interleukin -2 (IL-2) SNP and interleukin -10 (IL-10) SNP on HBV research point of view correlation correlation between HCC risk is not one. This study selected IL-2 rs2069763 gene and IL-10 gene rs1800872 locus, explore the 2 loci associated with HBV HCC. The relationship between transfer susceptibility, and to further explore the interaction between the two loci. The research method from November 2014 to August 2016, in the Qingdao municipal hospital selected the HBV Association of HCC in 263 patients (216 males) as the case group, 350 healthy subjects (284 males) collected by blood as the control group. Samples that subjects by polymerase chain reaction (PCR) and time of flight mass spectrometry (MALDI-TOF MS) to detect IL-2rs2069763 genotype IL-10 rs1800872. The general data were collected simultaneously, clinical data and laboratory examination indexes, using the statistical software SPSS 19, 2 Pearson x t test, Logistic test and regression analysis the methods of each genotype, gene loci and clinical data were analyzed. By using generalized multifactor dimensionality reduction (GMDR) software test of IL-2 gene and IL-10 gene loci SNP rs2069763 SNP rs1800872. The interaction of HBV. Results the correlation between HCC group compared with control group in gender, age, history of drinking, no statistically significant difference between the smoking history (P0.05) cases. The serum total protein and albumin index was significantly lower than the control group (P0.01), serum total bilirubin, direct bilirubin, indirect bilirubin, alanine transaminase, aspartate aminotransferase (AST), alkaline phosphatase (ALP) and glutamyl transpeptidase (GGT) levels were significantly higher than that of the control group (P0.01.IL-2) rs2060763 gene, the difference was statistically significant genotype frequency distribution of IL-10 gene rs1800872 locus and allele between case group and control group (P 0.05).Rs2069763G allele and rs1800872G allele could significantly increase the risk of HBV associated HCC (OR, 1.541,95%CI, 1.053 to 2.256, P=0.026, OR, 1.402,95%CI 1.011, to 1.943, P=0.043). After adjustment The confounding factors of age, sex, drinking and smoking, logistics regression analysis showed that the difference has statistical significance (OR, 1.605,95%CI 1.090, to 2.364, P=0.005; OR, 1.465,0.579,95%CI 1.052, to 2.041, P=0.006). The correlation between HBV in the HCC group, compared with non carriers of IL-2 gene rs2069763 allele G carriers have higher AST levels (P = 0.001) and higher levels of ALP (P0.001); rs1800872 IL-10 gene in the G allele of ALT (P = 0.020), AST (P = 0.011) and ALP (P = 0.024) of the higher level of.GMDR software test analysis showed that the interaction effect between IL-2 gene rs2069763 and IL-10 gene rs1800872 two loci interaction (P0.05), the influence that joint action of the two sites and not on the risk of HBC related HCC. Conclusion the Han population in Qingdao area Chinese, IL-2rs2069763G allele And IL-10rs1800872 G allele can increase the risk of HBV related HCC. There is no interaction between the.IL-2 gene rs2069763 locus and IL-10 gene rs1800872 locus on HBV related HCC vulnerability.

【學(xué)位授予單位】：大連醫(yī)科大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2017
【分類號(hào)】：R512.62;R735.7
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本文編號(hào)：1630622