Clin Cancer Res:顺铂诱导的严重神经毒性的临床和全基因组分析

2020-10-06 AlexYang MedSci原创

顺铂是许多癌症的一线化疗药物,但会引起神经毒性,包括听力损失、耳鸣和周围感觉神经病变。然而,到目前为止还没有研究综合描述发生多种(>1种)严重神经毒性的风险因素。

顺铂是许多癌症的一线化疗药物,但会引起神经毒性,包括听力损失、耳鸣和周围感觉神经病变。然而,到目前为止还没有研究综合描述发生多种(>1种)严重神经毒性的风险因素。

研究包括了300名接受顺铂治疗的睾丸癌幸存者。研究人员使用了逻辑回归评估了多重严重神经毒性与年龄、顺铂累积剂量、病史和生活方式/行为因素之间的关系,同时还进行了病例-对照GWAS分析(病例:104;对照:196)。研究结果表明,临床检查时的年龄(p=6.4x10-16)和累计顺铂剂量(p=5.4x10-4)与多重严重神经毒性风险呈现正相关关系。在调整了年龄和累计顺铂剂量后,高血清铂水平(p=0.02)、吸烟(曾经吸烟者:p=0.001,目前吸烟者:p=0.002)和高血压(p=0.01)也与之正相关。具有多重严重神经毒性的个体在调整了年龄和剂量后,更容易出现头晕/眩晕(p=0.01)、雷诺现象(p=3.7x10-9)和周围运动神经病变一致的症状(p=4.3x10-14)。另外,这些患者还报告了较差的整体健康状况(p=2.7x10-5)和更多的精神药物使用(p=0.06)。GWAS没有发现全基因组显著的SNPs。基于基因的关联分析发现RGS17(p=3.9x10-5)和FAM20C(p=5.5x10-5)接近全基因组显著。FAM20C表达的降低与肿瘤细胞系中顺铂敏感性的增加有关。

最后,研究人员指出,某些幸存者更容易受到顺铂诱导的神经毒性的影响,明显增加了出现众多影响生活质量的神经器官症状的可能性。全基因组分析发现FAM20C的遗传变异是一个潜在的重要风险因素。

原始出处:

Matthew R Trendowski , Heather E Wheeler , Omar El Charif et al. Clinical and Genome-Wide Analysis of Multiple Severe Cisplatin-Induced Neurotoxicities in Adult-Onset Cancer Survivors. Clin Cancer Res. Sep 2020

 

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    2020-10-11 ms3000000449926787

    很好的文章!

    0

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睾丸癌(TC)虽然仅占男性所有癌症的1%,却是影响15至35岁男性的最常见的实体瘤。根据疾病的分期,一般采取睾丸切除术或切除术结合放疗(RT)、铂类药物化疗(CT)的方式进行治疗。至顺铂(cispla