本文選題：原發(fā)性肝癌 + 乙型肝炎病毒�。� 參考：《中國(guó)疾病預(yù)防控制中心》2017年碩士論文

【摘要】：目的 了解原發(fā)性肝癌(Hepatocellular carcinoma,HCC)合并乙型肝炎病毒(Hepatitis B Virus,HBV)感染者的HBV基因特征狀況及其與肝癌的關(guān)系。方法2012-2015年在我國(guó)青海海南藏族自治州、廣西隆安縣、河北正定縣、上海黃浦區(qū)、河南開封市和湖南湘潭市建立HCC監(jiān)測(cè)網(wǎng)絡(luò),收集HCC合并HBV感染者作為肝癌組,同時(shí)從2012-2015年肝炎室全國(guó)乙肝監(jiān)測(cè)樣本庫(kù)中選擇相同地區(qū)的未患HCC和肝硬化(Liver cirrhosis,LC)的慢性乙型肝炎患者作為對(duì)照組。采用酶聯(lián)免疫吸附試驗(yàn)(Enzyme-linked immunosorbent assay,Elisa)檢測(cè)樣本的HBV感染指標(biāo)。利用QIAGEN公司的QIAamp DNA Blood Mini Kit試劑盒提取HBV脫氧核糖核酸(Deoxyribonucleic acid,DNA)并用巢氏聚合酶鏈反應(yīng)(Polymerase Chain Reaction,PCR)法擴(kuò)增 HBV 基因序列。雙向測(cè)序后用 DNAstar(SeqMan)軟件進(jìn)行序列拼接。并利用MEGA6軟件與從GeneBank中獲取的49株標(biāo)準(zhǔn)參照株序列進(jìn)行序列比對(duì)以確定基因型。用Bioedit軟件分析樣本序列的 C1653T、T1753V、A1762T/G1764A 雙突變、G1896A 和 PreS 缺失突變等位點(diǎn)的突變情況,并將PreS區(qū)核苷酸序列采用標(biāo)準(zhǔn)密碼子翻譯成氨基酸,觀察其序列情況。利用SPSS16.0軟件進(jìn)行統(tǒng)計(jì)分析。結(jié)果肝癌組共采集到血清546份,其中HBsAg陽性有334例,陽性率為61.2%。對(duì)照組則在每個(gè)地區(qū)采集25例,共150例,HBsAg均為陽性。肝癌組中86例樣本和對(duì)照組中39例樣本成功擴(kuò)增到目的基因序列HBV S區(qū)和基本核心啟動(dòng)子區(qū)(Basal core promoter,BCP)/Precore區(qū)。其中,肝癌組≥50歲占比高于對(duì)照組中≥50歲占比,組間差異有統(tǒng)計(jì)學(xué)意義(80.23%[69/86]比33.34%[13/39],χ2=26.153,P=0.000,OR=8.118;95%CI=3.465-19.019)。肝癌組中基因型C占比高于對(duì)照組中基因型C占比,組間差異有統(tǒng)計(jì)學(xué)意義(81.40%[70/86]比58.97%[23/39],χ2=9.961,P=0.002,OR=4.261,95%CI=1.667-10.889)。未發(fā)現(xiàn)性別、HBeAg 陽性率組間差異有統(tǒng)計(jì)學(xué)意義。肝癌組患者較對(duì)照組患者HBV前S缺失突變發(fā)病率高,差異有統(tǒng)計(jì)學(xué)意義。(34/86[39.53%]比 8/39[20.51%];χ2=4.350,P=0.037,OR=2.534;95%CI=1.041-6.166),進(jìn)一步分析發(fā)現(xiàn),只有PreS2缺失突變與HCC的發(fā)生是有統(tǒng)計(jì)學(xué)意義。(χ2=4.747,P=0.029,OR=3.506;95%CI=1.084-11.340)。HBVPreS1和PreS2起始密碼子缺失在與肝癌組和對(duì)照組中都存在。PreS缺失突變多發(fā)生在人血清白蛋白受體(88.10%[37/42])和S啟動(dòng)子(38.10%[16/42])、但較少發(fā)生在肝細(xì)胞結(jié)合位點(diǎn)(11.90%[5/42])和 CCAAT盒(9.52%[4/42])。肝癌組的A1762T突變率、A1762T/G1764A雙突變率分別為74.42%和72.09%,均高于對(duì)照組的53.85%和53.85%,差異有統(tǒng)計(jì)學(xué)意義,未發(fā)現(xiàn)兩組間G1764A、G1896A、T1753V突變的差異具有統(tǒng)計(jì)學(xué)意義�！�50歲年齡組的A1762T、A1762T/G1764A的突變率顯著高于50歲年齡組;基因型C的A1762T、G1764A、A1762T/G1764A的突變率顯著高于基因型B,而基因型B的G1896A突變率顯著高于基因型C。年齡≥50 歲[Adjusted odds ratio(AOR)=9.349,95%CI=3.329-26.257,P值=0.000]、基因型 C(AOR=28.875,95%CI=4.897-170.258,P值=0.000)和G1896A(AOR=7.648,95%CI=1.564-37.4,P值=0.012)是肝癌的獨(dú)立危險(xiǎn)因素。年齡≥50歲肝癌危險(xiǎn)性是年齡50歲的9.349倍,基因型C肝癌危險(xiǎn)性是基因型B的28.875倍,G1896A患肝癌危險(xiǎn)性是非突變者的7.648倍,而尚不能認(rèn)為性別、HBeAg、PreS 缺失突變、A1762T、G1764A、T1753V、A1762T/G1764A 是肝癌的獨(dú)立危險(xiǎn)因素。結(jié)論肝癌組患者中50歲占比和基因型C占比均高于對(duì)照組;肝癌組患者的PreS缺失突變、A1762T突變和A1762T/G1764A雙突變率均高于對(duì)照組;高年齡組和感染基因型C的人群發(fā)生A1762T、A1762T/G1764A的可能性更高;年齡≥50歲、基因型C、G1896A是肝癌的獨(dú)立的危險(xiǎn)因素,有更高的發(fā)生HCC風(fēng)險(xiǎn)。
[Abstract]:Objective To investigate the characteristics of HBV gene in patients with hepatocellular carcinoma ( HCC ) combined with hepatitis B virus ( HBV ) and its relationship with liver cancer . There was a statistically significant difference between the groups ( 80.23 % CI 69 / 86 vs 33.34 % CI 13 / 39 , 蠂2 = 26.153 , P = 0.000 , OR = 8.118 ; 95 % CI = 3.465 - 19.19 ) . The ratio of genotype C in HCC group was higher than that in control group ( 81.40 % vs 70 / 86 vs 58.97 % , 23 / 39 , 蠂2 = 9.961 , P = 0.002 , OR = 4.261 , 95 % CI = 1.667 - 10.889 ) . There was no significant difference between the positive rate of HBeAg and the positive rate of HBeAg in HCC group ( 34 / 86 , 39.53 % vs 8 / 39 , 20.51 % CI , 蠂2 = 4.350 , P = 0.037 , OR = 2.534 ; 95 % CI = 1.041 - 6.166 ) . It was found that only PreS2 deletion mutation was statistically significant with HCC . ( 蠂2 = 4.747 , P = 0.029 , OR = 3.506 ; 95 % CI = 1.084 - 11.340 ) . The mutation rates of A1762T , A1762T and A1762T / G1764 in HCC group were significantly higher than those in control group .

【學(xué)位授予單位】：中國(guó)疾病預(yù)防控制中心
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2017
【分類號(hào)】：R735.7;R512.62

【參考文獻(xiàn)】

相關(guān)期刊論文 前2條

1 Xin Zhang;Hui-Guo Ding;;Key role of hepatitis B virus mutation in chronic hepatitis B development to hepatocellular carcinoma[J];World Journal of Hepatology;2015年09期

2 Mustafa Sunbul;;Hepatitis B virus genotypes:Global distribution and clinical importance[J];World Journal of Gastroenterology;2014年18期

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本文編號(hào)：1803161