ERCC1和XPD单核苷酸多态性与非小细胞肺癌铂类化疗敏感性的关系

doi:10.3969/j.issn.1004-616x.2010.05.011

癌变·畸变·突变 ›› 2010, Vol. 22 ›› Issue (5): 374-378.doi: 10.3969/j.issn.1004-616x.2010.05.011

ERCC1和XPD单核苷酸多态性与非小细胞肺癌铂类化疗敏感性的关系

金艺凤1,李铁臣2,王　莹1,刘东华1,孙珍贵1

1.皖南医学院弋矶山医院呼吸内科，安徽芜湖 241001； 2.皖南医学院分子生物学研究室，安徽芜湖 241001

收稿日期:2010-05-12 修回日期:2010-07-02 出版日期:2010-09-30 发布日期:2010-09-30
通讯作者: 王　莹

Single nucleotide polymorphisms in ERCC1 and XPD genes and sensitivity to platinum_based chemotherapy in non_small_cell lung cancer

JIN Yi-feng1, LI Tie-chen2, WANG Ying1,,LIU Dong-hua11,SUN Zhen-gui1,

1. Department of Respiratory Medicine，the Affiliated Yijishan Hospital of Wannan Medical College, Wuhu 241001；2.Laboratory of Molecular Biology，Wannan Medical College，Wuhu 241001， Anhui， China

Received:2010-05-12 Revised:2010-07-02 Online:2010-09-30 Published:2010-09-30
Contact: WANG Ying

摘要/Abstract

摘要： 目的：探讨DNA修复基因ERCC1 C118T和XPD Lys751Gln单核苷酸多态性与非小细胞肺癌(non_small_cell lung carcinoma，NSCLC)患者对含铂方案化疗敏感性的关系。方法：选择经病理确诊为NSCLC的患者73例，在实施化疗前采取静脉血，提取DNA，行DNA测序、用PCR_RFLP方法检测ERCC1 C118T和XPD Lys751Gln基因型。所有患者均经含铂方案化疗，观察疗效，统计临床获益率，分析NSCLC患者ERCC1和XPD单核苷酸多态性与含铂方案化疗敏感性的关系。结果： ERCC1 C118T C/C、C/T 和 T/T 基因型临床获益率分别为94.9％、71.4％和83.8％。基因型C/C临床获益率明显高于C/T、T/T(P<0.05)。XPD Lys751Gln 基因型 Lys/Lys、Lys/Gln临床获益率分别为80.3％和75.0％。基因型Lys/Lys与Lys/Gln临床获益率间的差异无统计学意义(P=0.702)。未检测到XPD Gln/Gln基因型。ERCC1 C118T 、XPD Lys751Gln 多态之间在对含铂方案的化疗敏感性方面无协同作用(P=0.134和P=0.236)。结论： DNA修复基因ERCC1 C118T单核苷酸多态性与NSCLC含铂方案化疗的敏感性有关,可作为预测NSCLC患者铂类药物化疗敏感性的参考指标之一。

关键词: 切除修复交叉互补基因1, 着色性干皮病基因D, 非小细胞肺癌, 单核苷酸多态性, 顺铂

Abstract: OBJECTIVE: To investigate the relationship between single nucleotide polymorphisms of DNA repair genes ERCC1 C118T and XPD Lys751Gln and sensitivity to platinum_based chemotherapy in non_small_cell lung cancer(NSCLC). METHODS: A total of 73 patients with NSCLC were analyzed. All the patients were treated with platinum_based chemotherapy and the DNA of their peripheral blood was obtained before the therapy. ERCC1 and XPD genotypes were evaluated by DNA sequence and the polymerase chain reaction_restrictive fragment length polymorphism (PCR_RFLP) method. RESULTS: The clinical benefit rates to therapy among the patients with ERCC1 C118T C/C,C/T and T/T genotypes were 94.9％,71.4％and 83.3％, respectively . The clinical benefit rate of C/C genotype was significantly higher than C/T and T/T genotypes. There were significant differences in clinical benefit rates to platinum_based chemotherapy (P<0.05).The clinical benefit rates to therapy among the patients with XPD Lys751Gln Lys/Lys and Lys/Gln genotypes were 80.3％and 75.0％, respectively. There were no significant differences in clinical benefits to platinum_based chemotherapy(P=0.702).The XPD Gln/Gln genotype was not detected. There were no significant differences between the genetic polymorphisms and clinical benefits to platinum_based chemotherapy on ERCC1 C118T and XPD Lys751Gln(P=0.134 and P=0.236). CONCLUSION: Single nucleotide polymorphisms of ERCC1 C118T was associated with clinical response to platinum_based chemotherapy in NSCLC patients, suggesting the ERCC1 C118T SNP may be one of predictors for NSCLC patients who would be responsive to platinum agents.

Key words: ERCC1, XPD, non_small_cell lung carcinoma, single nucleotide polymorphisms, cisplatin

金艺凤, 李铁臣, 王　莹, 刘东华, 孙珍贵. ERCC1和XPD单核苷酸多态性与非小细胞肺癌铂类化疗敏感性的关系[J]. 癌变·畸变·突变, 2010, 22(5): 374-378.

JIN Yi-feng, LI Tie-chen, WANG Ying, , LIU Dong-hua, SUN Zhen-gui, . Single nucleotide polymorphisms in ERCC1 and XPD genes and sensitivity to platinum_based chemotherapy in non_small_cell lung cancer[J]. Carcinogenesis, Teratogenesis & Mutagenesis, 2010, 22(5): 374-378.

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ERCC1和XPD单核苷酸多态性与非小细胞肺癌铂类化疗敏感性的关系

Single nucleotide polymorphisms in ERCC1 and XPD genes and sensitivity to platinum_based chemotherapy in non_small_cell lung cancer

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