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目的探索DNA损伤修复基因Nei核酸内切酶Ⅷ样蛋白1(Nei endonucleaseⅧ-like 1,NEIL1)、人8-羟基鸟嘌呤糖苷酶1(human 8-hydroxygua-nine glycosylase,h OGG1)、背景瓣片状核酸内切酶1(flap structure-specific endonuclease 1,FEN1)、切除交叉互补基因2(excision repair cross complement,ERCC2)单核苷酸多态性与肺癌患者放射性肺炎的相关性。方法收集肺癌放疗患者167例,通过PCR测序法检测8个DNA修复基因单核苷酸多态性(NEIL1基因的rs4462560和rs7402844位点,h OGG1基因的rs1052133和rs293795位点,FEN1基因的rs174538和rs4246215位点,ERCC2基因的rs238406位点,ERCC5基因的rs2296147位点)。分析不同基因型与≥2级急性放射性肺炎的相关性,采用双荧光素报告基因实验研究ERCC5 5’UTR的单核苷酸多态性(single nucleotide polymorphism,SNP)对基因转录的影响。结果 167例肺癌放疗患者中,34例(20.4%)发生放射性肺炎。采用χ2检验和成组t检验分析放射性肺炎组和非放射性肺炎组两组间临床参数和物理参数,差异均无统计学意义(均P>0.05)。回归分析表明,ERCC5基因的rs2296147位点CC、CT以及CT/CC基因型都与≥2级急性放射性肺炎有相关性(P<0.05),而携带TT基因型患者未发现与≥2级急性放射性肺炎有相关性(P>0.05)。荧光素酶报告基因实验结果显示,ERCC5基因的rs2296147位点CC型降低ERCC5基因的转录水平。结论 ERCC5 rs2296147多态性与肺癌放射性肺炎存在相关性,可能作为预测肺癌放射性肺炎发生风险的指标,为肺癌的放射性治疗提供个体化治疗依据。
Objective To explore the expression of Nei endonuclease VIII-like 1 (NEIL1), human 8-hydroxygua-nine glycosylase (h OGG1), background flap Flap structure-specific endonuclease 1 (FEN1), excision repair cross complement (ERCC2) single nucleotide polymorphisms and radiation pneumonitis in patients with lung cancer. Methods One hundred and sixty-seven patients with radiotherapy of lung cancer were collected. Eight DNA repair gene SNPs were detected by PCR (rs4462560 and rs7402844 of NEIL1 gene, rs1052133 and rs293795 h of OGG1 gene, rs174538 of FEN1 gene, rs4246215, rs238406 of ERCC2 and rs2296147 of ERCC5). The association between different genotypes and grade 2 acute radiation pneumonitis was analyzed. The dual fluorescein reporter gene was used to study the effect of single nucleotide polymorphism (SNP) of ERCC5 5’UTR on gene transcription. Results Of 167 patients with lung cancer, 34 (20.4%) patients developed radiation pneumonitis. The χ2 test and group t test were used to analyze the clinical parameters and physical parameters between the two groups of radiation pneumonitis group and non-radiation pneumonitis group, the difference was not statistically significant (all P> 0.05). Regression analysis showed that the CC, CT and CT / CC genotypes of rs2296147 locus in ERCC5 gene were all associated with grade 2 acute radiation pneumonitis (P <0.05), but those with TT genotype were not associated with grade 2 acute radioactivity Pneumonia was related (P> 0.05). The results of luciferase reporter assay showed that the rs2296147 CC genotype of ERCC5 reduced the transcription level of ERCC5 gene. Conclusion The association between rs2296147 polymorphism of ERCC5 and radiation pneumonitis in lung cancer may be used as an index to predict the risk of radiation pneumonitis in lung cancer and provide a basis for individualized radiotherapy for lung cancer.