非小细胞肺癌RAD51、ERCC2和BAG-1基因多态性的表达

摘要

Objective:To study the relationship between Bcl-2 associated athanogene 1( BAG-1 ),xeroderma pigmentosum group D( ERCC2/XPD)and DNA repair gene RAD51 polymorphism and genetic susceptibility to non-small cell lung cancer( NSCLC ). Methods:A case - control study among 100 NSCLC cases and 80 controls matched by age and gender was conducted. The polymerase chain reaction-restriction fragment length polymorphism ( PCR-RFLP)was used to analyze the genetic polymorphisms. Logistic regression model was employed to calculate the odd ratios( ORs)and 95% confidence intervals( CIs)of ERCC2/XPD Lys751Gln,BAG -1 codon 324 and RAD51 codon 135 with susceptibility of NSCLC. Results:The allele frequencies of C/C,C/A,and A/A of ERCC2/XPD 751Gln were 69%(69/100),26%(26/100)and 5%(5/100)in cases,respectively. The odds ratios for individ-uals 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 allele frequencies of C/C,C/T and T/T of BAG-1 codon 324 were 81%(81/100),19%(19/100)and 0%(0/100) in cases,respectively. 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). A significant interaction was found between ERCC2/XPD Lys751Gln polymorphism and smoking and air pollution in NSCLC. Conclusion:Genetic poly-morphism of ERCC2/XPD C/A,BAG-1 codon 324 C/T and RAD51 codon 135 G/C may be associated with the ge-netic susceptibility to NSCLC.%目的：研究DNA修复基因RAD51和着色性干皮病基因（ ERCC2/XPD）以及Bcl-2结合抗凋亡基因1（Bcl-2 associated athanogene 1，BAG-1）基因多态性与非小细胞肺癌（non-small cell lung cancer，NSCLC ）遗传易感性的关系。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。以ER-CC2/XPD Lys751Gln和RAD51 codon 135以及BAG-1codon 324基因多态性为研究位点，聚合酶链反应-限制性片段长度多态性（ PCR-RFLP）方法对多态性进行检测。应用Logistic回归计算OR值及95%CI，比较不同基因型与NSCLC发病风险的关系。结果：ERCC2/XPD 751基因型在病例组的分布频率为 C/C型69例（69%）、C/A型26例（30%）和A/A型5例（5%）。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NSCLC的危险度比值比（ odds ratio，OR）分别是1.53（95%CI：1.15-3.32）和0.58（95%CI：0.15-2.39）。BAG-1 codon 324基因型的分布频率为 C/C型81%（81/100）、C/T型19%（19/100）以及T/T型0%（0例）。与野生基因型C/C型相比，携带BAG-1 C/T基因型者患NSCLC的OR是1.28（95%CI：1.08-2.74）。RAD51 codon 135基因型的分布频率为 G/G 型67%（67/100）、G/C 型33%（33/100）、未现C/C型。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）。分析结果提示吸烟、环境危险因素与XPD Lys751Gln基因多态存在交互作用，交互效应OR值分别为2.24（95%CI：1.18-2.87）和2.53（95%CI：1.71-3.46），携带XPD Ly s751Gln突变基因者若同时暴露于吸烟、环境危险因素下，则患NSCLC的危险显著增加，相较未暴露于上述因素者，OR 值均增大。结论：BAG-1和ERCC2/XPD以及RAD51基因多态性可能与当地居民NSCLC遗传易感性有关，ERCC2/XPD与吸烟、饮酒、环境危险因素存在交互作用。