在晚期非小细胞肺癌中XRCC1和XPD基因多态性的联合和铂类化疗的关系

Relationship between the combination of XRCC1 and XPD gene polymorphisms with platinum-based chemotherapy in advanced non-small cell lung cancer

目的探讨DNA修复基因XRCC1和XPD两种基因多态性的联合与接受铂类治疗的非小细胞肺癌(NSCLC)患者临床疗效及生存时间的关系。方法对接受铂类治疗的108例ⅢB期和Ⅳ期NSCLC患者,利用聚合酶链反应(PCR)结合限制性片段长度多态性(RFLP)来检测XRCC1第399位点和XPD第751位点基因多态性,通过电话随访等方式获得患者的生存状态,以STATA软件分析比较基因多态性与铂类化疗疗效及生存时间的关系。结果在所有接受含铂药物治疗的患者中,化疗总有效率为21.6%。携带XRCC1 Arg/Gln基因型和XPD Lys/Gln基因型的患者有更高有效率(33.33%),但此类患者与其他各种基因型患者相比,化疗有效率的差异无统计学意义(P>0.05)。Cox比例风险模型显示,携带XRCC1 Arg/Gln基因型和XPD Lys/Gln基因型的患者中位生存时间(MST)最长35.5个月,但与其他基因型患者相比,MST差异无统计学意义(P>0.05)。结论同时携带XRCC1 Arg/Gln和XPD Lys/Gln基因型的NSCLC患者,使用含铂方案化疗可能有更高的有效率和更长的生存期。但此结果仍需扩大样本进一步验证。

Objective To investigate the relationship between combination of X-ray repair cross complementing group 1（XRCC1） and xeroderma pigmentosum group D（XPD） genetic polymorphisms and chemotherapy response and survival time in non-small cell lung cancer（NSCLC） patients.Methods Polymerase chain reaction-restriction fragment length polymorphism（PCR-RFLP） was used to detect genetic polymorphisms of the XRCC1 Arg399Gln and XPD Lys751Gln DNA repair genes in 108 patients with stage ⅢB and Ⅳ NSCLC treated with platinum-based chemotherapy.Survival status of patients was obtained through follow-ups by telephone contact.The relationship between genetic polymorphisms and chemotherapy response and survival duration after platinum-based chemotherapy were analyzed by STATA software.Results Among NSCLC patients treated with platinum-based chemotherapy,the overall response rate of chemotherapy was 21.6%.The patients with XRCC1 Arg/Gln and XPD Lys/Gln genotype were associated with a higher response rate（33.33%）,but no statistical significant difference was found among these patients and other genotypes patients（P0.05）.Estimation by Cox proportional hazards model showed the patients with XRCC1 Arg/Gln and XPD Lys/Gln genotype had a higher median survival duration（MST）（35.5 months）.However,compared with other genotypes patients,the difference of MST had no statistical significance（P0.05）.Conclusion The patients with combination of XRCC1 399Arg/Gln and XPD Lys/Gln genotype may have higher treatment response and survival duration in advanced NSCLC patients with platinum-based chemotherapy.Further verification of this result is still required,though.