非小细胞肺癌中RAD51、ERCC2和BAG-1基因多态性与临床病理特征的关系

摘要

目的：探讨DNA损伤修复基因RAD51和切除修复交叉互补基因（ERCC2）/着色性干皮病基因（XPD ）ERCC2/XPD以及Bcl-2结合抗凋亡基因1（BAG-1）基因多态性与非小细胞肺癌临床病理特征的关系。方法采用病例对照研究设计，选取100例非小细胞肺癌病例和80例正常对照。选取ERCC2/XPD Lys751Gln和RAD51 codon 135以及BAG-1codon 324基因多态性为研究位点，以聚合酶链反应-限制性片段长度多态性（PCR-RFLP）方法进行多态性检测，应用Logistic回归计算OR值及95％CI，比较不同基因型与非小细胞肺癌发病风险的关系，并分析与非小细胞肺癌临床病理学特征的相关性。结果与野生基因型C/C型相比，携带ERCC2/XPD C/A基因型和A/A基因型者患非小细胞肺癌的OR分别是1．53（95％CI：1．15～3．32）和0．58（95％CI：0．15～2．39）；与野生基因型G/G型相比，RAD51 G/C基因型者患NSCLC的OR是1．03（95％CI：1．06～2．29）。与野生基因型C/C型相比，携带BAG-1C/T基因型者患NSCLC的OR是1．28（95％ CI：1．08～2．74）；ER-CC2/XPD C/A和A/A基因型多态性与淋巴结转移状态有相关性（P＝0．038，OR＝2．26，95％CI：1．69～3．59）；与远处转移几率的相关性更好P＝0．005，OR＝2．47，95％CI：1．38～4．24）。BAG-1 codon 324 C/T型，RAD51 codon 135 G/C型基因多态性与淋巴结转移状态有相关性（P＝0．042，OR＝2．57，95％CI：1．62～4．44和P＝0．049和OR＝2．86，95％CI：1．39～3．62）。结论 DNA损伤修复基因ERCC2/XPD和RAD51以及BAG-1基因多态性增加了非小细胞肺癌发生的风险，ERCC2/XPD和RAD51以及BAG-1基因多态性改变与非小细胞肺癌患者的淋巴结及远处转移密切相关。%Obj ective To explore the relationship between xeroderma pigmentosum group D (ERCC2/XPD),Bcl-2 associated athanogene 1 (BAG-1 )and DNA repair gene RAD5 1 polymor-phism and clinicopathological characteristics of non-small cell lung cancer (NSCLC).Methods A case-control study with 100 NSCLC cases and 80 controls matched by age and sex was conducted, the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP )was ana-lyzed.Logistic regression model was made to calculate the odd ratios (ORs)and detect 95%confi-dence intervals (CIs)of ERCC2/XPD Lys751Gln,BAG-1codon 324 and RAD51 codon 135 with susceptibility of NSCLC.Unconditional Logistic regression model adj usted by the confounding fac-tors was used to analyze the correlation between the polymorphism genotypes and the risk of NSCLC and clinicopathological characteristics.Results The odds ratios for individuals carrying ERCC2/XPD C/A and A/A were 1.53(95%CI:1.15~3.32)and 0.58 (95% CI:0.15~2.39).The odds ratios for individuals carrying BAG-1 C/T was 1.28(95%CI:1.08~2.74).The odds ratios for individuals carrying RAD51 G/C was 1.03(95%CI:1.06~2.29).ERCC2/XPD C/A and A/A polymorphisms genotype frequencies were significantly related to the invasive characteristics of NSCLC [lymph node metastasis:(P= 0.038,OR= 2.26,95% CI:1.69~3.59),distant metastasis:(P= 0.005,OR= 2.47,95%CI:1.38~4.24)].As the same BAG-1 codon 324 C/T and RAD51 codon 135 G/C polymorphisms genotype frequencies (P= 0.042,OR= 2.57, 95%CI:1.62~4.44 and P= 0.049,OR= 2.86,95%CI:1.39~3.62).Conclusion Genet-icpolymorphism of ERCC2/XPD,BAG-1 and RAD5 1 are associated with the susceptibility to NSCLC.ERCC2/XPD,BAG-1 and RAD51gene polymorphism in Chinese Han population in-creases susceptibility to NSCLC risk and the changes of ERCC2/XPD C/A and A/A,BAG-1codon 324 C/T and RAD51 codon 135 G/C polymorphism are closely related to lymph node and distant metastasis.