文章摘要

ABC转运蛋白基因多态性与晚期非小细胞肺癌铂类药物化疗的相关性

作者: 1乔荣, 2吴文婷, 2卢大儒, 1韩宝惠
1 上海交通大学附属胸科医院呼吸内科，上海 200030
2 复旦大学生命科学学院，遗传工程国家重点实验室，现代人类学教育部重点实验室，上海 200438
通讯: 韩宝惠 Email: xkyyhan@gmail.com
DOI: 10.3978/j.issn.2095-6959.2016.01.008

摘要

目的：研究ABC转运蛋白基因多态性与晚期含铂方案化疗的非小细胞肺癌(non-small cell lung cancer，NSCLC)患者化疗敏感性和耐受性的关系。方法：经病理学确诊的III/IV期NSCLC患者240例，采用顺铂或卡铂为主的方案进行化疗，2个周期后进行临床疗效和毒副反应评价。用MASS-ARRAY的方法进行MDR1 C3435T、MDR1 C1236T、BCRP C421A、MRP2 I1324I和MRP2−24C>T多态性的分型。用SPSS软件分析不同基因型与化疗敏感性和毒副反应的相关性。比值比(odds ratios，OR)及 95% CI以logistic回归模型计算。结果：MRP2−24C>T C/T型客观缓解率(objective response rate，ORR)显著降低(P=0.026，OR=3.036，95% CI：1.143~8.061)；MRP2 I1324I A/G型更容易出现血小板减少P=0.028，OR=6.829，95% CI：1.232~37.869)；MRP2−24C>T C/T型更容易出现血小板减少(P=0.029，OR=6.592，95% CI：1.217~35.695)。结论：MRP2 I1324I、MRP2−24C>T多态性可以预测非小细胞肺癌患者对含铂方案化疗的缓解率和骨髓抑制情况。
关键词： 单核苷酸多态性 ABC转运蛋白基因 非小细胞肺癌 化学疗法 药物敏感性 药物耐受性

The correlation between single nucleotide polymorphism of ABC transporter and response rate and severe toxicity in lung cancer patients treated with platinum-based chemotherapy

Authors: 1QIAO Rong, 2WU Wenting, 2LU Daru, 1HAN Baohui
1 Department of Respiratory Disease, Chest Hospital of Shanghai Jiaotong University, Shanghai 200030
2 State Key Laboratory of Genetic Engineering and Key Laboratory of Contemporary Anthropology, School of Life Sciences, Fudan University, Shanghai 200438, China

CorrespondingAuthor: HAN Baohui Email: xkyyhan@gmail.com

DOI: 10.3978/j.issn.2095-6959.2016.01.008

Abstract

Objective: To investigate the relationship between genetic polymorphisms of ATP-binding cassette (ABC) and the response rate and the occurrence of grade 3 or 4 toxicity in stage III and IV non-small cell lung cancer (NSCLC) patients treated with platinum-based chemotherapy. Methods: A total of 240 patients with advanced NSCLC were treated with cisplatin or carboplatin based on chemotherapy. Clinical response and grade 3 or 4 toxicity were evaluated after two cycles. MDR1 C3435T, MDR1 C1236T, BCRP C421A, MRP2 I1324I and MRP2−24C>T were determined by MASS-ARRAY methods. The odds ratios (OR) and 95% confidence interval (CI) were computed by logistic regression. Results: The objective response rate to chemotherapy in patients with MRP2−24C>T C/T was higher than that in patients with C/C (P=0.026, OR=3.036, 95% CI: 1.143~8.061). The risk of 3 or 4 thrombocytopenia was lower in patients with MRP2 I1324I A/G (P=0.028, OR=6.829, 95% CI: 1.232~37.869) and MRP2−24C>T C/T (P=0.029, OR=6.592, 95% CI: 1.217~35.695). Conclusion: Polymorphisms of MRP2−24C>T and MRP2 I1324I might be used to predict the objective response rate or 3 or 4 thrombocytopenia in patients with advanced NSCLC after treatment with platinum-based chemotherapy.

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