Pharmacy Department, University Hospital of Santiago (SERGAS), Santiago de Compostela, Spain.
Clinical Pharmacology Group, Health Research Institute of Santiago de Compostela (IDIS), Santiago de Compostela, Spain.
Head Neck. 2019 Aug;41(8):2704-2715. doi: 10.1002/hed.25754. Epub 2019 Apr 11.
Platinum-based chemoradiotherapy (CRT) is the standard treatment for locally advanced head and neck squamous-cell carcinomas (HNSCC), and most patients experience serious toxicities. The aim of this study was to investigate the association between candidate genes involved in radiation/platinum pathways and acute toxicity of CRT to determine the predictive value of these polymorphisms for toxicity.
Thirty-six selected single nucleotide polymorphisms (SNPs) in 29 genes were genotyped in 110 patients treated with cisplatin-based CRT. DNA was obtained from blood samples, and SNP analysis was performed using a MassARRAY iPLEX Gold (Sequenom) method.
Patients with ERCC1 rs11615-C allele (P = .0066), ERCC1 rs735482-C allele (P = .0204), and ERCC4 rs1799801-C allele (P = .0286) had lower risk of grade 2-3 hematologic toxicity. In addition, the presence of G allele of GSTP1 was associated with a significantly lower risk of severe dysphagia (P = .0004).
Polymorphisms in ERCC1 and GSTP1 may act as prognostic factors of acute toxicity during treatment with CRT in HNSCC patients.
含铂的放化疗（CRT）是局部晚期头颈部鳞状细胞癌（HNSCC）的标准治疗方法，大多数患者会经历严重的毒性反应。本研究旨在探讨与辐射/铂途径相关的候选基因多态性与 CRT 急性毒性之间的关系，以确定这些多态性对毒性的预测价值。
对 110 例接受顺铂为基础的 CRT 治疗的患者进行了 29 个基因中的 36 个候选单核苷酸多态性（SNP）的基因分型。从血液样本中提取 DNA，采用 MassARRAY iPLEX Gold（Sequenom）方法进行 SNP 分析。
携带 ERCC1 rs11615-C 等位基因（P =.0066）、ERCC1 rs735482-C 等位基因（P =.0204）和 ERCC4 rs1799801-C 等位基因（P =.0286）的患者发生 2-3 级血液学毒性的风险较低。此外，GSTP1 基因的 G 等位基因与严重吞咽困难的风险显著降低相关（P =.0004）。
ERCC1 和 GSTP1 基因的多态性可能是 HNSCC 患者 CRT 治疗中急性毒性的预后因素。
