Fang Chao, Li Xiang-Ping, Gong Wei-Jing, Wu Na-Yiyuan, Tang Jie, Yin Ji-Ye, Li Xi, Zhang Wei, Zhou Hong-Hao, Liu Zhao-Qian
Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, China.
Institute of Clinical Pharmacology, Central South University, Hunan Key Laboratory of Pharmacogenetics, Changsha, China.
Clin Exp Pharmacol Physiol. 2017 Dec;44 Suppl 1:21-29. doi: 10.1111/1440-1681.12704. Epub 2017 Sep 20.
Platinum-based chemotherapy toxicity severely impedes successful treatment in lung cancer patients. MicroRNAs (miRs) have a significant impact on the occurrence and survival rate of lung cancer. The purpose of this study was to investigate the association between common miRNA variants and platinum-based chemotherapy toxicity in lung cancer patients. A total of eight functional single nucleotide polymorphisms (SNPs) of miRNA were genotyped in 408 lung cancer patients by MALDI-TOF mass spectrometry. All the patients were histologically confirmed as lung cancer, and were treated with platinum-based chemotherapy for at least two cycles. It was found that the polymorphism rs2042553 of miR-5197 had a significant association with overall severe toxicity in both additive (P=.031, odds ratio [OR]=1.41, 95% confidence interval [CI] 1.03-1.93) and dominant (P=.009, OR=1.80, 95% CI 1.16-2.80) models. MiR-605 rs2043556 was significantly related to severe hepatotoxicity in dominant model (P=.022, OR=2.51, 95% CI 1.12-4.14). In addition, rs2910164 of miR-146a had marginal statistical effect on severe hepatotoxicity in additive model (P=.054). The subgroup analyses showed that miR-27a rs895819 was related to gastrointestinal toxicity in age >56 years old, smoking and non-smoking patients. Taken together, our results revealed that polymorphisms of miR-5197, miR-605, miR-146a, and miR-27a contributed to the chemotherapy toxicity of lung cancer, which may serve as a predictive tool for toxicity evaluation of platinum-based chemotherapy in lung cancer patients.
铂类化疗毒性严重阻碍肺癌患者的成功治疗。微小RNA（miRs）对肺癌的发生和生存率有重大影响。本研究的目的是调查肺癌患者中常见miRNA变异与铂类化疗毒性之间的关联。通过基质辅助激光解吸电离飞行时间质谱法对408例肺癌患者的8个功能性微小RNA单核苷酸多态性（SNPs）进行基因分型。所有患者均经组织学确诊为肺癌，并接受至少两个周期的铂类化疗。研究发现，miR - 5197的多态性rs2042553在加性模型（P = 0.031，比值比[OR]=1.41，95%置信区间[CI] 1.03 - 1.93）和显性模型（P = 0.009，OR = 1.80，95% CI 1.16 - 2.80）中均与总体严重毒性显著相关。miR - 605 rs2043556在显性模型中与严重肝毒性显著相关（P = 0.022，OR = 2.51，95% CI 1.12 - 4.14）。此外，miR - 146a的rs2910164在加性模型中对严重肝毒性有边缘统计学效应（P = 0.054）。亚组分析显示，miR - 27a rs895819与年龄>56岁的吸烟和非吸烟患者的胃肠道毒性有关。综上所述，我们的结果表明，miR - 5197、miR - 605、miR - 146a和miR - 27a的多态性导致了肺癌的化疗毒性，这可能作为肺癌患者铂类化疗毒性评估的预测工具。
