ERCC1和ERCC4基因多态性对NSCLC患者顺铂疗效的影响

中国临床药理学与治疗学 ›› 2011, Vol. 16 ›› Issue (7): 772-778.

ERCC1和ERCC4基因多态性对NSCLC患者顺铂疗效的影响

华之卉^1,2, 房文铮³, 赵忠全³, 解方为³, 欧阳学农³, 宋洪涛¹

¹南京军区福州总医院药学科,福州 350025,福建;
²沈阳药科大学药学院,沈阳 110016,辽宁;
³南京军区福州总医院肿瘤科,福州350025,福建

收稿日期:2011-04-06 修回日期:2011-06-17 出版日期:2011-07-26 发布日期:2011-09-22
通讯作者: 宋洪涛,男,博士,主任药师,博导,主要从事药剂学和临床药学方面的研究。Tel: 0591-22859459 E-mail: sohoto@vip.sohu.com
作者简介:华之卉,女,硕士研究生,研究方向:临床药学。Tel: 0591-22859972 E-mail: zhihui19998@126.com

Association study of ERCC1 and ERCC4 genetic polymorphism with response and survival in non-small cell lung cancer patients treated with cisplatin-based chemotherapy

HUA Zhi-hui^1,2, FANG Wen-zheng³, ZHAO Zhong-quan³, XIE Fang-wei³, OU YANG Xue-nong³, SONG Hong-tao¹

¹Department of Pharmacy,Fuzhou General Hospital of Nanjing Command, Fuzhou 350025,Fujian, China;
²School of Pharmacy,Shenyang Pharmaceutical University,Shenyang 110016,Liaoning, China;
³Department of Oncology,Fuzhou General Hospital of Nanjing Command, Fuzhou 350025, Fujian, China

Received:2011-04-06 Revised:2011-06-17 Online:2011-07-26 Published:2011-09-22

摘要/Abstract

摘要： 目的: 探讨ERCC1 C118T、ERCC4 -673C>T基因多态性对以顺铂为基础化疗的非小细胞肺癌(NSCLC)患者疗效的影响。方法: 采用多聚酶链反应-限制片断长度多态性(PCR-RFLP)法对接受以顺铂为基础化疗的NSCLC患者进行基因分型,并评价其化疗疗效及疾病进展情况,然后分析基因多态性与化疗疗效的相关性。结果: 虽然未发现NSCLC患者ERCC1 C118T基因型间客观有效率及疾病控制率的差异,仍然可以看到携带C/C基因患者的客观有效率及疾病控制率均高于携带T突变等位基因患者(T/T+C/T)(29.6% vs 20.6%,77.8% vs 73.5%),而NSCLC患者无进展生存期(PFS)与ERCC1 C118T基因多态性无关联性。携带ERCC4-673C>T野生型(C/C)患者疾病控制率略低于携带T等位基因型(C/T+T/T)患者(72.5% vs 81.0%),但无统计学差异。未发现以顺铂为基础化疗的NSCLC患者客观有效率、PFS与ERCC4-673C>T基因多态性有关。结论: 以顺铂为基础化疗的NSCLC患者疗效与ERCC1 C118T、ERCC4-673C>T基因多态性可能无关。

关键词: 非小细胞肺癌, 顺铂, 基因多态性, ERCC1, ERCC4

Abstract: AIM: To evaluate the effect of the polymorphisms of excision repair cross-complementation group 1(ERCC1) and excision repair cross-complementation group 4 (ERCC4) on response and progress free survival in non-small cell lung cancer patients treated with cisplatin-based chemotherapy.METHODS: ERCC1 and ERCC4 were genetyped by polymerase chain reaction restriction fragment length polymorphism. The relationship between response, progress free survival and genetype was analyzed.RESULTS: Compared with patients carrying C/T and T/T in ERCC1 C118T, carrying genotype C/C were more likely respond to chemotherapy(20.6% vs 29.6%; 77.8% vs 73.5%) , but there is no significant difference in response and progress free survival in patients at ERCC1 C118T genotype. Compared with patients carrying C/T and T/T in ERCC4 -673C>T, carrying genotype C/C tended to get less clinical benefit from chemotherapy(72.5% vs 81.0%), any associativity between ERCC4 -673C>T genotype and response, progress free survival in patients receiving cisplatin based chemotherapy was unfounded.CONCLUSION: Genetic polymorphism of ERCC1 and ERCC4 were not associated with response and progress free survival in non-small cell lung cancer patients treated with cisplatin-based chemotherapy.

Key words: Non-small cell lung cancer, Cisplatin, Genetic polymorphism, ERCC1, ERCC4

中图分类号:

R969

华之卉, 房文铮, 赵忠全, 解方为, 欧阳学农, 宋洪涛. ERCC1和ERCC4基因多态性对NSCLC患者顺铂疗效的影响[J]. 中国临床药理学与治疗学, 2011, 16(7): 772-778.

HUA Zhi-hui, FANG Wen-zheng, ZHAO Zhong-quan, XIE Fang-wei, OU YANG Xue-nong, SONG Hong-tao. Association study of ERCC1 and ERCC4 genetic polymorphism with response and survival in non-small cell lung cancer patients treated with cisplatin-based chemotherapy[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2011, 16(7): 772-778.

参考文献

[1] 赵刚涛,杨凡,丁媛媛,等.单核苷酸多态性对非小细胞肺癌铂类化疗敏感性的影响的研究进展[J].中国临床药理学与治疗学,2010,15(6) :715-720.
[2] Ryu JS, Hong YC, Han HS, et al. Association between polymorphisms of ERCC1 and XPD and survival in non-small cell lung cancer patients treated with cisplatin combination chemotherapy[J].Lung Cancer,2004,44(3):311-316.
[3] Tibandi C, Giovannetti E, Vasile E,et al.Correlation of CDA, ERCC1, and XPD polymorphisms with response and survival in gemcitabine/cisplatin-treated advanced non-small cell lung cancer patients[J].Clin Cancer Res, 2008,14(6) :1797-1803.
[4] 柳艳飞,管晓翔,陈龙邦,等.ERCC1 与 XPD 和 XPA 的遗传多态性对非小细胞肺癌铂类化疗敏感性预测的研究[J].中华肿瘤防治杂志,2008,15(17) :1285-1288.
[5] Wang JH, Zhang Q, Zhang H, et al. Association between polymorphisms of ERCC1 and response in patients with advanced non-small cell lung cancer receiving cisplatin-based chemotherapy[J]. Chin J Lung Cancer, 2010,13(4): 337-341.
[6] 于典科. ERCC1和XPF功能性遗传变异肺癌易感性及铂类药疗效相关[D].中国协和医科大学研究生院博士研究生学位论文,2008.
[7] Therasse P, Arbuck SA, Eisenhauer EA, et al. New guidelines to evaluate the response treatment in solid tumors[J]. J Natl Cancer Inst,2000,92(3):205-216.
[8] 涂向东,江清华,兰风华.三种简易提取全血基因组DNA方法的比较[J].中国实验诊断学,2006,10(3):264-266.
[9] 陈健,何义富,胡冰.核苷酸切除修复基因多态性和铂类药物耐药性关系研究进展[J].现代肿瘤医学,2009,17(4):763-766.
[10] Kalikaki A, Kanka M, Vassalou H, et al. DNA repair gene polymorphisms predict favorable clinical outcome in advanced non-small-cell lung cancer[J]. Clin Lung Cancer,2009,10(2):118-123.
[11] Su D, Ma S, Liu P,et al.Genetic polymorphisms and treatment response in advanced non-small cell lung cancer[J].Lung Cancer,2007,56(2):281-288.
[12] Park DJ,Zhang W,Stoehlmaeher J,et al.ERCCI gene polymorphism as a predictor for clinical outcome in advanced coloreetal cancer patients treated with platinum-based chemotherapy[J].Clin Adv Hematol Oncol,2003,1(3):162-166.
[13] Okuda K, Sasaki H, Hikosaka Y,et al. Excision repair cross complementation group 1 polymorphisms predict overall survival after platinum-based chemotherapy for completely resected non-small-cell lung cancer[J]. J Surg Res, 2011, 168(2):206-212.
[14] Li F, Sun X, Sun N, et al. Association between polymorphisms of ERCC1 and XPD and clinical response to platinum-based chemotherapy in advanced non-small cell lung cancer[J]. Am J Clin Oncol, 2010 , 33(5):489-494.
[15] Wei SZ, Zhan P, Shi MQ,et al. Predictive value of ERCC1 and XPD polymorphism in patients with advanced non-small cell lung cancer receiving platinum-based chemotherapy: a systematic review and meta-analysis[J]. Med Oncol, 2011,28(1):315-321.
[16] Yin M, Yan J, Voutsina A, et al. No evidence of an association of ERCC1 and ERCC2 polymorphisms with clinical outcomes of platinum-based chemotherapies in non-small cell lung cancer: A meta-analysis[J]. Lung Cancer, 2011,72(3):370-377.