Prediction of copper transport protein 1 (CTR1) genotype on severe cisplatin induced toxicity in non-small cell lung cancer (NSCLC) patients.
Prediction of copper transport protein 1 (CTR1) genotype on severe cisplatin induced toxicity in non-small cell lung cancer (NSCLC) patients.
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DOI：
10.1016/j.lungcan.2012.03.023
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发表时间：
2012-08
期刊：
影响因子：
5.3
通讯作者：
Xiaojing Xu;Huayi Ren;Boting Zhou;Yingchun Zhao;Ruixia Yuan;R. Ma;Honghao Zhou;Zhaoqian Liu
中科院分区：
文献类型：
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作者：
Xiaojing Xu;Huayi Ren;Boting Zhou;Yingchun Zhao;Ruixia Yuan;R. Ma;Honghao Zhou;Zhaoqian Liu
背景顺铂毒性严重阻碍肺癌患者化疗的成功。顺铂的摄取被认为是导致顺铂副作用的主要因素之一。核心基因的遗传变异也会影响顺铂的毒性。已确定 CTR1（铜转运蛋白 1）在顺铂摄取中发挥重要作用。本研究的目的是调查非小细胞肺癌（NSCLC）患者中CTR1多态性是否与铂类毒性相关。METHOD纳入来自三个不同机构的204例NSCLC患者并进行随访。这些患者经组织学证实患有非小细胞肺癌。所有患者均接受了至少两个周期的顺铂化疗。在这些患者中检测到了20个CTR1 SNP。 结果TCTR1 rs10981694 A>C多态性与顺铂在NSCLC患者中引起的严重毒性相关。 C 携带者受试者对耳毒性的耐受性较差 (p<0.05)。不同rs10981694基因多态性患者的生存时间无显着差异。结论携带CTR1 rs10981694 C等位基因的NSCLC患者在顺铂治疗后对耳毒性更敏感。 CTR1 在顺铂毒性中发挥重要作用，可被视为肺癌患者治疗前评估的预测因子。
BACKGROUNDCisplatin toxicity severely obstacles successful chemotherapy in lung cancer patients. Cisplatin uptake is considered as one of the major factors contributing to the side effects of cisplatin. Genetic variances of core genes also affect cisplatin toxicity. It has been identified that CTR1, copper transporter protein 1, plays an essential role in cisplatin uptake. The purpose of this study is to investigate whether CTR1 polymorphism is associated with platinum toxicity in non-small cell lung cancer (NSCLC) patients.METHOD204 incident NSCLC patients from three different institutions were enrolled and followed up. These patients were histologically confirmed with non-small cell lung cancer. All patients have accepted cisplatin-based chemotherapy for at least two cycles. Twenty SNPs of CTR1 were detected in these patients.RESULTCTR1 rs10981694 A>C polymorphism is associated with cisplatin induced severe toxicity in NSCLC patients. C-carrier subjects presented poorer tolerance to ototoxicity (p<0.05). The survival times of patients with different rs10981694 genetic polymorphism were not significantly different.CONCLUSIONNSCLC patients carrying C allele of CTR1 rs10981694 presented more sensitivity to ototoxicity after cisplatin treatment. CTR1 plays an essential role in cisplatin toxicity and could be considered as a predictor for pretreatment evaluation in lung cancer patients.