西南地区肺癌放疗患者放射性肺炎与相关基因单核苷酸多态性位点之间的关联研究

发布时间：2018-05-23 16:43

本文选题：肺癌 + 放疗　；参考：《川北医学院》2016年硕士论文

【摘要】：目的:筛查影响中国西南地区肺癌放疗人群发生放射性肺炎(radiation pneumonitis,RP)的易感基因单核苷酸多态性位点(single nucleotide polymorphism,SNP),以用于放疗前对肺癌患者进行RP风险评估与预测。方法:以重庆大坪医院肿瘤科和成都军区总医院肿瘤诊治中心接受胸部放疗的肺癌患者为研究对象,进行放疗后至少3个月的随访,以不良反应常用术语3.0版(Common Terminology Criteriafor Adverse Eventsv3.0,CTCAE 3.0)为标准评估患者发生RP的严重程度。每位患者的基因组DNA样本来源于外周抗凝血的提取。选择的40个SNPs的基因分型采用多重高温连接酶检测反应技术(improved multiple ligase detection reaction,i MLDR)方法进行双盲检测。SNPs与RP的关联分析及位点间的交互作用采用cox比例风险模型分析,Kaplan-Meier用于计算基因型发生RP的累积风险。P≤0.05认为有统计学意义。结果:本研究共募集合格样本305例,其中≥2级RP发病率为18.7%(57人),≥3级RP发病率为7.9%(24人)。301例DNA样本成功进行了基因分型检测。对于发生2级以上RP的各类风险因素关联分析结果显示:临床因素中,年龄≥65岁、PS≥3、吸烟、V845%、V1030%、V1525%、V2018%及V3010%均分别与发生≥2级RP的风险具有显著相关性。遗传因素的关联分析显示,突变型等位基因IL1B rs1143623G、TNFRSF1B rs1061622 G、MIF rs755622 C及IL6 rs2069840杂合型CG基因型携带者发生≥2级RP的风险比其野生纯合子携带者显著增加。各位点交互作用分析的结果显示:rs1143623GC*rs1061622GT、rs1061622GT*rs 755622GC、rs1143623GC*rs755622GC、rs1143623GC*rs755622CC和rs1143623GG*rs2069840CC在发生≥2级RP发展过程中存在正交互作用。对发生≥3级RP与各类风险因素关联分析结果显示:突变型等位基因TNFRSF1B rs1061622 G、MIF rs755622 C、EGFR rs2075112 G、及IL13 rs20541突变型TT基因型携带者发生≥3级RP的风险比位点其它基因型携带者的发生风险显著增加,等位基因EGFR rs11977660 T和TNF rs1799724 CT基因型携带者发生≥3级RP风险明显小于该位点其它基因型携带者。这些位点各基因型之间的交互作用分析结果显示:rs1061622TT*rs2075112AG、rs1061622TT*rs755622 GC、rs11977660CT*rs755622CC、rs20541TT*rs 2075112AG、rs20541CT*rs755622CC、rs2075112AG*rs755622GC、rs2075112AG*rs755622CC和rs2075112 GG*rs755622CC在≥3级RP发生过程中存在正交互作用。结论:1、临床因素中,年龄、PS评分、吸烟、V8、V10、V15、V20及V30可能是≥2级RP的危险因素。2、单因素分析表明基因IL1B rs1143623G/C、TNFRSF1B rs1061622G/T、MIF 755622G/C和IL6 rs2069840C/G遗传多态性位点与西南地区肺癌放疗患者发生≥2级RP的风险具有显著相关性,经多因素校正后IL1B rs1143623G/C和MIF 755622G/C仍与≥2RP显著相关。两位点间基因型rs1143623GC*rs1061622GT、rs1061622GT*rs 755622GC、rs1143623GC*rs755622GC、rs1143623GC*rs755622CC和rs1143623GG*rs2069840CC在≥2级RP发生过程中存在协同作用。3、单因素分析发现多态性位点IL13 rs20541C/T、TNFRSF1B rs1061622G/T、MIF 755622G/C和TNF rs1799724C/T遗传多态性位点与西南地区肺癌放疗患者发生≥3级RP具有显著相关性,经多因素校正后MIF 755622G/C、EGFRrs2075112A/G和EGFR rs11977660C/T与≥3级RP风险显著相关。两位点间基因型rs1061622TT*rs2075112AG、rs1061622TT*rs755622GC、rs11977660CT*rs755622CC、rs20541TT*rs2075112AG、rs20541CT*rs 755622CC、rs2075112AG*rs755622GC、rs2075112AG*rs755622CC和rs2075112 GG*rs755622CC在≥3级RP的发生过程中存在协同作用。
[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.
【学位授予单位】：川北医学院
【学位级别】：硕士
【学位授予年份】：2016
【分类号】：R734.2

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