DNA修复酶XRCC1基因多态与非小细胞肺癌对GP方案化疗的敏感性

Polymorphisms in XRCC1 Gene and Sensitivity to Gemcitabine/Cisplatin Chemotherapy in Non Small Cell Lung Cancer

目的研究DNA修复酶XRCC1基因Codon194和Codon399多态与非小细胞肺癌(NSCLC)患者对吉西他滨/顺铂(GP)方案化疗敏感性的关系。方法收集经病理学确诊的NSCLC57例,所有病例化疗前抽静脉血,提取白细胞DNA,用PCR-RFLP技术检测XRCC1194和399基因型。所有患者均经PDD/GEM化疗方案治疗。结果①NSCLC患者中,XRCC1194Arg/Arg、Arg/Trp、Trp/Trp基因型者分别为30例(52.6%)、23例(40.4%)和4例(7.0%);XRCC1399Arg/Arg、Arg/Gln、Gln/Gln基因型者分别为31例(54.4%)、23例(40.3%)和3例(5.3%)。经化疗后,19例患者有效,总有效率33.3%。②XRCC1194Trp/Trp、Tp/Arg和Arg/Arg基因型者的化疗有效率分别为50.0%、52.2%和16.7%。携带Trp等位基因者的化疗有效率(51.9%)显著高于Arg/Arg基因型者(χ2=6.41,P=0.0113);XRCC1399Arg/Arg、Arg/Gln和Gln/Gln基因型者的化疗有效率分别为35.5%、34.8%和0,各组间的差异无显著性。XRCC1194与XRCC1399多态之间在化疗敏感性方面存在明显的交互作用,同时携带194Arg/Arg和399Arg/Arg基因型者的化疗有效率仅为7.7%(1/13),而同时携带XRCC1194Trp等位基因和399Arg/Arg基因型者的化疗有效率为58.8%(10/17),2组之间差异显著(Fisher’s双侧检验P=0.0067)。结论DNA修复酶基因XRCC1多态与NSCLC对GP方案化疗的敏感性有关,患者的基因型检测有可能作为预测NSCLC对GP方案化疗敏感性的指标。

Objective To investigate the relationship between genetic polymorphisms in X-ray repair cross-complementing group 1 （XRCC1） codons 194 and 399 and response to gemcitabine/cisplatin （GP regimen） chemotherapy in non small cell lung cancer （NSCLC）. Methods 57 patients with NSCLC were analyzed. All patients were treated with GP regimen chemotherapy and DNA of peripheral blood leukocytes was obtained before therapy. XRCC1 codons 194 and 399 genotypes were detected by PCRRFLP method. Results ①Of all cases, the frequencies of XRCC1 codon 194 Arg/Arg, Arg/Trp and Trp/Trp genotype were 52.6% ,40.4% and 7.0%, while the frequencies of XRCC1 codon 399 Arg/Arg, Arg/Gln and Gin/Gin genotypes were 54.4%, 40.3% and 5.3% ,respectlvely.The overal response rate to chemotherapy in all of patients was 33.3%.② The response rate to therapy among patients with XRCC1 codon 194 Arg/Arg,Arg/Trp and Trp/Trp genotypes were 16.7% ,52.2% and 50.0% ,respectively. The response rate to therapy among patients with XRCC1 codon 194 Trp allele （51.9 % ） was significantly higher compared with that among patients with the Arg/Arg genotype （ 16.7 %, X^2 = 6.41, P = 0.0113 ）. No significant different in response rate to therapy was observed among patients with XRCC1 codon 399 Arg/Arg,Arg/Gln and Gin/Gin genotypes. And yet there is a cooperate action between codon 194 and 399 polymorphisms. The rcsponse rate to therapy among patients with the codon 194 Trp allele and codon 399 Arg/Arg genotype （58.8%） was significantly higher compared with that among patients with the codon 194 Arg/Arg and codon 399 Arg/Arg genotype （7.7 %, Fisher exact test two side P = 0. 0067）. Conclusion These results in the present study suggested that the polymorphisms of the XRCC1 were associated with clinical response to GP regimen chemotherapy ,suggesting that XRCC1 genotypes could identify advanced NSCLC patients that would be responsive to GP regimen chemotherapy.