本文選題：肺癌 + 放療�。� 參考：《川北醫(yī)學(xué)院》2016年碩士論文

【摘要】：目的:篩查影響中國(guó)西南地區(qū)肺癌放療人群發(fā)生放射性肺炎(radiation pneumonitis,RP)的易感基因單核苷酸多態(tài)性位點(diǎn)(single nucleotide polymorphism,SNP),以用于放療前對(duì)肺癌患者進(jìn)行RP風(fēng)險(xiǎn)評(píng)估與預(yù)測(cè)。方法:以重慶大坪醫(yī)院腫瘤科和成都軍區(qū)總醫(yī)院腫瘤診治中心接受胸部放療的肺癌患者為研究對(duì)象,進(jìn)行放療后至少3個(gè)月的隨訪,以不良反應(yīng)常用術(shù)語(yǔ)3.0版(Common Terminology Criteriafor Adverse Eventsv3.0,CTCAE 3.0)為標(biāo)準(zhǔn)評(píng)估患者發(fā)生RP的嚴(yán)重程度。每位患者的基因組DNA樣本來(lái)源于外周抗凝血的提取。選擇的40個(gè)SNPs的基因分型采用多重高溫連接酶檢測(cè)反應(yīng)技術(shù)(improved multiple ligase detection reaction,i MLDR)方法進(jìn)行雙盲檢測(cè)。SNPs與RP的關(guān)聯(lián)分析及位點(diǎn)間的交互作用采用cox比例風(fēng)險(xiǎn)模型分析,Kaplan-Meier用于計(jì)算基因型發(fā)生RP的累積風(fēng)險(xiǎn)。P≤0.05認(rèn)為有統(tǒng)計(jì)學(xué)意義。結(jié)果:本研究共募集合格樣本305例,其中≥2級(jí)RP發(fā)病率為18.7%(57人),≥3級(jí)RP發(fā)病率為7.9%(24人)。301例DNA樣本成功進(jìn)行了基因分型檢測(cè)。對(duì)于發(fā)生2級(jí)以上RP的各類風(fēng)險(xiǎn)因素關(guān)聯(lián)分析結(jié)果顯示:臨床因素中,年齡≥65歲、PS≥3、吸煙、V845%、V1030%、V1525%、V2018%及V3010%均分別與發(fā)生≥2級(jí)RP的風(fēng)險(xiǎn)具有顯著相關(guān)性。遺傳因素的關(guān)聯(lián)分析顯示,突變型等位基因IL1B rs1143623G、TNFRSF1B rs1061622 G、MIF rs755622 C及IL6 rs2069840雜合型CG基因型攜帶者發(fā)生≥2級(jí)RP的風(fēng)險(xiǎn)比其野生純合子攜帶者顯著增加。各位點(diǎn)交互作用分析的結(jié)果顯示:rs1143623GC*rs1061622GT、rs1061622GT*rs 755622GC、rs1143623GC*rs755622GC、rs1143623GC*rs755622CC和rs1143623GG*rs2069840CC在發(fā)生≥2級(jí)RP發(fā)展過(guò)程中存在正交互作用。對(duì)發(fā)生≥3級(jí)RP與各類風(fēng)險(xiǎn)因素關(guān)聯(lián)分析結(jié)果顯示:突變型等位基因TNFRSF1B rs1061622 G、MIF rs755622 C、EGFR rs2075112 G、及IL13 rs20541突變型TT基因型攜帶者發(fā)生≥3級(jí)RP的風(fēng)險(xiǎn)比位點(diǎn)其它基因型攜帶者的發(fā)生風(fēng)險(xiǎn)顯著增加,等位基因EGFR rs11977660 T和TNF rs1799724 CT基因型攜帶者發(fā)生≥3級(jí)RP風(fēng)險(xiǎn)明顯小于該位點(diǎn)其它基因型攜帶者。這些位點(diǎn)各基因型之間的交互作用分析結(jié)果顯示:rs1061622TT*rs2075112AG、rs1061622TT*rs755622 GC、rs11977660CT*rs755622CC、rs20541TT*rs 2075112AG、rs20541CT*rs755622CC、rs2075112AG*rs755622GC、rs2075112AG*rs755622CC和rs2075112 GG*rs755622CC在≥3級(jí)RP發(fā)生過(guò)程中存在正交互作用。結(jié)論:1、臨床因素中,年齡、PS評(píng)分、吸煙、V8、V10、V15、V20及V30可能是≥2級(jí)RP的危險(xiǎn)因素。2、單因素分析表明基因IL1B rs1143623G/C、TNFRSF1B rs1061622G/T、MIF 755622G/C和IL6 rs2069840C/G遺傳多態(tài)性位點(diǎn)與西南地區(qū)肺癌放療患者發(fā)生≥2級(jí)RP的風(fēng)險(xiǎn)具有顯著相關(guān)性,經(jīng)多因素校正后IL1B rs1143623G/C和MIF 755622G/C仍與≥2RP顯著相關(guān)。兩位點(diǎn)間基因型rs1143623GC*rs1061622GT、rs1061622GT*rs 755622GC、rs1143623GC*rs755622GC、rs1143623GC*rs755622CC和rs1143623GG*rs2069840CC在≥2級(jí)RP發(fā)生過(guò)程中存在協(xié)同作用。3、單因素分析發(fā)現(xiàn)多態(tài)性位點(diǎn)IL13 rs20541C/T、TNFRSF1B rs1061622G/T、MIF 755622G/C和TNF rs1799724C/T遺傳多態(tài)性位點(diǎn)與西南地區(qū)肺癌放療患者發(fā)生≥3級(jí)RP具有顯著相關(guān)性,經(jīng)多因素校正后MIF 755622G/C、EGFRrs2075112A/G和EGFR rs11977660C/T與≥3級(jí)RP風(fēng)險(xiǎn)顯著相關(guān)。兩位點(diǎn)間基因型rs1061622TT*rs2075112AG、rs1061622TT*rs755622GC、rs11977660CT*rs755622CC、rs20541TT*rs2075112AG、rs20541CT*rs 755622CC、rs2075112AG*rs755622GC、rs2075112AG*rs755622CC和rs2075112 GG*rs755622CC在≥3級(jí)RP的發(fā)生過(guò)程中存在協(xié)同作用。
[Abstract]:Objective: to screen the susceptibility gene polymorphic loci (single nucleotide polymorphism, SNP) of radiation pneumonitis (RP) for lung cancer patients in Southwest China, and to evaluate and predict the risk of RP in patients with lung cancer before radiotherapy. Methods: the oncology department of Daping Hospital in Chongqing and the general Chengdu Military Area Military region. At least 3 months after radiotherapy, the lung cancer patients who received chest radiotherapy at the hospital tumor diagnosis and treatment center were followed up for at least 3 months. The severity of RP was assessed by the 3 version of the commonly used term for adverse reactions (Common Terminology Criteriafor Adverse Eventsv3.0, CTCAE 3). The extraction of anticoagulant. The 40 SNPs genotyping used multiple high temperature ligase detection reaction technique (improved multiple ligase detection reaction, I MLDR) to double blind detection of the association analysis of.SNPs and RP and the interaction between loci and Cox proportional hazard model analysis. Kaplan-Meier was used to calculate genotypic occurrence. The cumulative risk of P was.P less than 0.05. Results: a total of 305 qualified samples were recruited in this study, among which the incidence of RP above 2 levels was 18.7% (57) and 7.9% (24) with 7.9% (24) and 7.9% (24). The correlation analysis of various risk factors for RP above 2 levels showed: clinical factors: clinical factors The risk of smoking, smoking, V845%, V1030%, V1525%, V2018% and V3010% were correlated with the risk of RP more than 2, respectively. The correlation analysis of genetic factors showed that the mutant allele IL1B rs1143623G, TNFRSF1B rs1061622 G, and the carriers of the heterozygous genotype genotype were more than 2 levels of RP. The results of interaction analysis showed that rs1143623GC*rs1061622GT, rs1061622GT*rs 755622GC, rs1143623GC*rs755622GC, rs1143623GC*rs755622CC and rs1143623GG*rs2069840CC have positive interaction in the development of RP higher than grade 2. The risk of mutant alleles TNFRSF1B rs1061622 G, MIF rs755622 C, EGFR rs2075112 G, and IL13 rs20541 mutant TT genotypes were significantly higher than those of other genotype carriers. The risk of more than 3 levels of RP was significantly smaller than that of other genotype carriers of the site. The interaction analysis between the genotypes of these loci showed that rs1061622TT*rs2075112AG, rs1061622TT*rs755622 GC, rs11977660CT*rs755622CC, rs20541TT*rs 2075112AG, rs20541CT* rs755622CC, rs2075112AG*rs755622GC, rs2075112AG*rs755622CC, and rs20 75112 GG*rs755622CC has positive interaction in the course of the occurrence of RP. Conclusion: 1. In clinical factors, age, PS score, smoking, V8, V10, V15, V20 and V30 may be a risk factor for the 2 grade RP.2. There is a significant correlation between the risk of more than 2 grade RP for lung cancer patients in southern China. After multifactor correction, IL1B rs1143623G/C and MIF 755622G/C are still associated with greater than 2RP. The genotype rs1143623GC*rs1061622GT, rs1061622GT*rs 755622GC, rs1143623GC*rs755622GC, rs1143623GC*rs755622CC and rs1143623GG*rs2069840CC are more than 2 after two loci. Single factor analysis found that polymorphic loci of polymorphic loci IL13 rs20541C/T, TNFRSF1B rs1061622G/T, MIF 755622G/C and TNF rs1799724C/T were significantly correlated with the occurrence of > 3 level RP of lung cancer patients in Southwest China. 11977660C/T was significantly related to the risk of RP above 3. The genotype rs1061622TT*rs2075112AG, rs1061622TT*rs755622GC, rs11977660CT*rs755622CC, rs20541TT*rs2075112AG, rs20541CT*rs 755622CC, rs2075112AG*rs755622GC, rs2075112AG*rs755622CC and rs2075112 GG* between the two loci were synergistic in the occurrence of > 3.
【學(xué)位授予單位】：川北醫(yī)學(xué)院
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2016
【分類號(hào)】：R734.2

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