ERCC5 rs2296147多态性与肺癌患者急性放射性肺炎的相关性研究  

Single nucleotide polymorphism of ERCC5 rs2296147 is associated with incidence of acute radiation pneumonitis in lung cancer patients

作　　者：陈亚楠[1] 左云[1] 周芳[1] 沈冬[1] 何雪平[1] 张永芹[1] 徐丽贤[1] 夏秋燕 梁素莹 

机构地区：[1]张家港市第一人民医院肿瘤科,江苏张家港215600 [2]张家港市澳洋医院肿瘤科,江苏张家港215600

出　　处：《实用肿瘤杂志》2016年第3期255-262,共8页Journal of Practical Oncology

基　　金：张家港市科技支撑计划(ZKS1316)

摘　　要：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 investigate the association of single nucleotide polymorphisms（ SNPs） of DNA repair genes,Nei endonuclease Ⅷ-like 1（ NEIL1）,human 8-hydroxygua-nine glycosylase（ h OGG1）,flap structure-specific endonuclease 1（ FEN1） and excision repair cross complement（ ERCC2）,with acute radiation pneumonitis in lung cancer patients. Methods One-hundred-and-sixty-seven lung cancer patients receiving radiotherapy were enrolled in the study. The single nucleotide polymorphisms of 8 DNA repair genes（ NEIL1： rs4462560 and rs7402844; h OGG1： rs1052133 and rs293795; FEN1： rs174538 and rs4246215; ERCC2： rs238406,and ERCC5： rs2296147） were detected by polymerase chain reaction and DNA sequencing. The correlation between the genotypes and the incidence of ≥grade 2 acute radiation pneumonitis were analyzed. Dual luciferase reporter gene assay was used to examine the effect of the SNPs in the 5＇UTR region of ERCC5 on gene transcription. Results Of the 167 patients with lung cancer,34 patients（ 20. 4%） developed radiation pneumonia. No significant differences in clinical parameters or physical parameters were detected between the patients with radiation pneumonitis and those without radiation pneumonitis（ control group） shown by χ^2test or t tests（ P〉0. 05）.Logistic regression analysis suggested that CC,CT and CT / CC genotypes of ERCC5 rs2296147 were correlated with ≥grade2 acute radiation pneumonia（ P〈0. 05）,but TT genotype of the same location has no correlation with ≥grade 2 acute radiation pneumonia（ P〉0. 05）. Dual luciferase reporter gene assay showed that the transcription level of ERCC5 was downregulated in patients with CC genotype of ERCC5 rs2296147. Conclusion SNPs of ERCC5 rs2296147 was related to radiation pneumonitis in lung cancer patients,which may be a new indicator to predict the risks of radiation pneumonitis.

关 键 词：肺肿瘤/放射疗法 DNA修复 DNA损伤 基因 多态性 单核苷酸 辐射性肺炎/预防和控制 辐射性肺炎/病因学 急性病 

分 类 号：R734.2[医药卫生—肿瘤] R730.55[医药卫生—临床医学]