Li Yue-Qin, Zhang Xin-Yin, Chen Juan, Yin Ji-Ye, Li Xiang-Ping
Department of Pharmacy; Department of Clinical Pharmacology, Xiangya Hospital, Central South University; Institute of Clinical Pharmacology, Central South University, Changsha, PR China.
Department of Clinical Pharmacology, Xiangya Hospital, Central South University; Institute of Clinical Pharmacology, Central South University, Changsha, PR China.
J Cancer Res Ther. 2018;14(4):881-886. doi: 10.4103/jcrt.JCRT_890_17.
Platinum-based chemotherapy is considered as the first-line treatment for nonsmall cell lung cancer (NSCLC) patients. However, platinum resistance and toxicity are major obstacles to its clinical applications. The two P-type ATPases ATP7A and ATP7B have been identified to play an essential role in the transport of platinum. Their genetic polymorphisms may affect the treatment outcome and toxicity of platinum. In this study, we aimed to investigate the association of ATP7A and ATP7B genetic polymorphisms with clinical outcome and toxicity of platinum-based chemotherapy in NSCLC patients.
Four hundred and twenty-seven NSCLC patients were enrolled. All patients have accepted platinum-based chemotherapy for at least two cycles. ATP7A (rs2227291 and rs6622665) and ATP7B (rs1061472 and rs9535826) polymorphisms were genotyped by allele-specific matrix-assisted laser desorption ionization-time-of-flight mass spectrometry. Chemotherapeutic response, overall survival time, and hematological and gastrointestinal toxicity were recorded and their associations with genetic factors were evaluated.
ATP7A rs2227291 and rs6622665 deviated from Hardy-Weinberg equilibrium. Therefore, the two single-nucleotide polymorphisms were not taken into consideration. For ATP7B polymorphism, ATP7B rs9535826 was associated with gastrointestinal toxicity, and the GG genotype showed lower gastrointestinal toxicity (odds ratio = 0.30; 95% confidence interval = 0.10-0.90; P = 0.031).
The genotypes of ATP7B gene may be novel and significant biomarkers for predicting the gastrointestinal toxicity of platinum-based chemotherapy in NSCLC patients.
铂类化疗被认为是非小细胞肺癌（NSCLC）患者的一线治疗方法。然而，铂耐药性和毒性是其临床应用的主要障碍。已确定两种P型ATP酶ATP7A和ATP7B在铂的转运中起重要作用。它们的基因多态性可能影响铂类治疗的疗效和毒性。在本研究中，我们旨在探讨ATP7A和ATP7B基因多态性与NSCLC患者铂类化疗的临床疗效和毒性之间的关联。
纳入427例NSCLC患者。所有患者均接受了至少两个周期的铂类化疗。采用等位基因特异性基质辅助激光解吸电离飞行时间质谱法对ATP7A（rs2227291和rs6622665）和ATP7B（rs1061472和rs9535826）多态性进行基因分型。记录化疗反应、总生存时间以及血液学和胃肠道毒性，并评估它们与遗传因素的关联。
ATP7A的rs2227291和rs6622665偏离了哈迪-温伯格平衡。因此，未考虑这两个单核苷酸多态性。对于ATP7B多态性，ATP7B rs9535826与胃肠道毒性相关，GG基因型显示较低的胃肠道毒性（比值比=0.30；95%置信区间=0.10-0.90；P=0.031）。
ATP7B基因的基因型可能是预测NSCLC患者铂类化疗胃肠道毒性的新型重要生物标志物。
