切除修复交叉互补基因1和着色性干皮病基因多态性与晚期非小细胞肺癌铂类药物化疗敏感性的关系研究

目的探讨切除修复交叉互补基因1(ERCC1)、着色性干皮病基因(XPD)多态性与晚期非小细胞肺癌(NSCLC)患者含铂二药方案化疗敏感性的关系。方法采用PCR-RFLP方法检测130例以铂类药物为基础化疗方案的晚期NSCLC患者ERCC1 118C/T、C8092A与XPD Asn312Asp、Lys751Gln基因多态性,分析其与化疗敏感性的关系。结果化疗2个周期后,130例患者的客观缓解率(ORR)为33.8%(44/130),其中部分缓解(PR)44例(33.8%),疾病稳定(SD)54例(41.6%),疾病进展(PD)32例(24.6%)。ERCC1 118C/T+T/T基因型化疗ORR(52.4%)是C/C基因型(41.8%)的3.300倍95%CI(1.104,9.864),P=0.003]。XPD Asp312Asn、Lys751Gln(或Gln751Gln)基因型化疗ORR(62.5%)是其他基因型的(29.2%)的3.922倍95%CI(1.320,11.649),P=0.010]。ERCC1 118C/T(或T/T)、XPD Asp312Asn与Lys751Gln(或Gln751Gln)基因型化疗ORR(58.0%)是ERCC1 118C/C、XPD Asp312Asp与Lys751Lys基因型的(31.8%)的3.571倍95%CI(1.082,11.793),P=0.032]。应用SHEsis分析软件发现以其他单体型组为参照,A-C单体型化疗ORR显著提高(P=0.039)。结论 ERCC1 118C/T和XPD Asp312Asn、Lys751Gln多态性与晚期NSCLC患者铂类药物化疗敏感性密切相关。

Relationship between ERCC1 and XPD Genetic Polymorphism and Sensitivity of Platinum-Based Chemotherapy in Advanced Non-Small Cell Lung Cancer

Objective To investigate the relationship between genetic polymorphism of excision repair cross-complementing(ERCC1) and xeroderma pigmentosum group D(XPD) and platinum-based chemotherapy in advanced non-small cell lung cancer(NSCLC).Methods Genetic polymorphisms of ERCC1 118 C/T,C8092A and XPD Asn312Asp,Lys751Gln were detected by PCR-RFLP method in 130 patients with advanced NSCLC who received platinum-based chemotherapy and the relationship between genetic polymorphisms of ERCC1 and XPD and chemotherapy sensitivity was analyzed.Results After two chemotherapy cycles,the overall response rate is 33.8%(44/130),including 44 PR(33.8%),54 SD(41.6%) and 32 PD(24.6%).The ERCC1 118 C/T+T/T carriers were 3.300 times as sensitive to the chemotherapy as the C/C genotype 95%CI(1.104,9.864),P=0.003].The XPD Asp312Asn and Lys751Gln(or Gln751Gln) carriers were 3.922 times as sensitive to the chemotherapy as the other types 95%CI(1.320,11.649),P=0.010].The ERCC1 118 C/T(or T/T),XPD Asp312Asn and Lys751Gln(or Gln751Gln) polymorphism carriers were 3.571 times as sensitive to the chemotherapy as the ERCC1 118 C/C,XPD Asp312Asp and Lys751Lys polymorphism carriers 95%CI(1.082,11.793),P=0.032].The effective rate of chemotherapy of the patients with A-C haplotype were significantly increased compared with other haplotypes(P=0.039).Conclusion There is close relationship between polymorphism in ERCC1 118C/T and polymorphisms in XPD Asp312Asn,Lys751Gln and response of patients with advanced NSCLC receiving platinum-based chemotherapy.