XPD基因单核苷酸多态性与晚期非小细胞肺癌对铂类药物敏感性的关系

Relationship between XPD single nucleotide polymorphisms and platinum sensitivity in advanced non-small-cell lung cancer

目的研究DNA修复基因着色性干皮病基因(XPD)Lys751Gln和XPD Asp312Asn基因多态性与非小细胞肺癌化疗铂类敏感性的关系。方法收集经病理学确诊的晚期非小细胞肺癌87例,所有病例化疗前抽静脉血,提取DNA,用多聚酶链反应-限制性片段长度多态性(PCR-RFLP)分析技术检测XPD Lys751Gln和XPD Asp312Asn基因型,比较不同基因型与铂类化疗疗效的关系及与无进展生存时间的关系。结果总有效率43.7%,CR 3例(3.45%),PR 35例(40.23%),SD 20例(22.99%),PD 29例(33.33%),携带XPD751Lys/Lys、Lys/GIn基因型的患者,客观有效(CR+PR)分别为36例(48.6%)、2例(15.4%)二者相比差异有统计学意义(P=0.026)。携带XPD 312Asp/Asp、Asp/Asn基因型的患者,客观有效(CR+PR)分别为35例(40.23%)、3例(30.0%)二者相比差异无统计学意义(P=0.556)。携带XPD751 Lys/Lys、Lys/Gln与XPD312 Asp/Asp、Asp/Asn基因型的患者无进展生存时间(PFS)分别为6.7和5.9个月、6.5和6.4个月,无统计学意义(P=0.170、P=0.674)。Cox回归模型分析显示XPD751位点基因型为Lys/Gln的患者疾病进展风险是基因型为Lys/Lys的患者的2.383倍(P=0.006)。XPD751位点基因型为Lys/Gln可能是疾病进展较早的因素。结论 XPD Lys751Gln单核苷酸多态性与晚期非小细胞肺癌铂类药物耐药有关。未发现XPD基因单核苷酸多态性与无进展生存时间相关,但XPD751位点基因型为Lys/Gln可能是疾病进展较早的危险因素。

Objective To investigate the relationship between polymorphisms of DNA repair gene XPD Lys 751 Gln,XPD Asp 312 Asn and sensitivity platinum in advanced non-small-cell lung cancer（NSCLC）.Methods XPD Lys751Gln and XPD Asp 312 Asn were genotyped by PCR-RFLP method in 87 patients with advanced NSCLC who received platinum-based chemotherapy,and the association between genotypes and response was evaluated.Results Genotype frequencies of XPD 751 were Lys/Lys 85.06%（74/87）,Lys/Gln 14.94%（13/87） and XPD 312 were Asp/Asp 45.5%,Asp/Asn 30.0%. Response rate of patients carrying with Lys/Lys in XPD 751 was 48.6%,15.4% with Lys/Gln.The XPD751 Lys/Lys allele carriers had higher chemosensitivity to platinum than the cases presenting with Lys/Gln genotype（OR=2.041,95%CI=1.371~34.999）.There was no correlation between XPD312 gene polymorphisms and chemosensitivity to platinum.There was difference in progression free survival between patients carrying with Lys/Lys and Lys/Gln in XPD 751 but XPD 751 was a critical factor for progression free survival.Conclusions There is association between polymorphisms in XPD response in patients with advanced NSCLC receiving cisplatin-based chemotherapy.