Candidate apoptotic and DNA repair gene approach confirms involvement of ERCC1, ERCC5, TP53 and MDM2 in radiation-induced toxicity in head and neck cancer
Candidate apoptotic and DNA repair gene approach confirms involvement of ERCC1, ERCC5, TP53 and MDM2 in radiation-induced toxicity in head and neck cancer
复制标题
DOI：
10.1016/j.oraloncology.2017.02.003
复制
发表时间：
2017-04-01
期刊：
影响因子：
4.8
通讯作者：
Milano, G.
中科院分区：
文献类型：
--
作者：
Borchiellini, D.;Etienne-Grimaldi, M. C.;Milano, G.
简介：DNA修复和凋亡基因的单核苷酸多态性（SNP）与接受放疗（RT）的头颈部鳞状细胞癌（HNSCC）患者的预后相关。我们的目标是进行候选基因研究HNSCC患者接受RT或chemoRT.Methods：122非切除HNSCC患者接受RT（N = 38）或chemoRT（N = 84）之间1992年和2006年进行了回顾性分析。在肿瘤DNA上分析ERCC 1 Lys 259 Thr（rs735482）、ERCC 2 Lys 751 Gln（rs 13181）、ERCC 5 His 46 His C > T（rs 1047768）、XRCC 1 Arg 399 Gln（rs 25487）、TP 53 Arg 72 Pro（rs 1042522）和MDM 2 309 T> G（rs 2279744）。结果：120例可评价的患者在任何时间均发生了RT相关毒性反应。其中83%的患者在放疗过程中出现了G3-4级急性副作用，主要为吞咽困难、粘膜炎、上皮增生和/或口干（DMEX）。28/105例（27%）患者在RT结束后3个月内发生了3 -4级早期毒性，29/96例（30%）患者在RT结束后3个月内发生了3 -4级晚期毒性。MDM 2的G等位基因或ERCC 1的Thr等位基因的存在与急性和/或早期DMEX毒性的风险显著增加相关。MDM 2 309 GG基因型与急性G3-4皮炎的高风险相关。ERCC 5 TT基因型与更常见的G3-4晚期颈部皮肤纤维化或口干症相关。结论：DNA修复（ERCC 1和ERCC 5）和凋亡（MDM 2和TP 53）基因的相关SNP可能影响HNSCC患者放射性骨坏死的严重程度。在这些基础上，需要进行前瞻性的基于SNP的临床验证研究。(C)2017爱思唯尔有限公司版权所有
Introduction: Single nucleotide polymorphisms (SNPs) of DNA repair and apoptosis genes have been associated with outcome in head and neck squamous cell carcinoma (HNSCC) patients receiving radiotherapy (RT). Our goal was to conduct a candidate gene study in HNSCC patients receiving RT or chemoRT.Methods: 122 non-resectable HNSCC patients undergoing RT (N = 38) or chemoRT (N = 84) between 1992 and 2006 were retrospectively analyzed. ERCC1 Lys259Thr (rs735482), ERCC2 Lys751Gln (rs13181), ERCC5 His46His C > T (rs1047768), XRCC1 Arg399Gln (rs25487), TP53 Arg72Pro (rs1042522) and MDM2 309T > G (rs2279744) were analyzed on tumor DNA. SNP profile was considered to assess RT-related toxicity.Results: All 120 evaluable patients experienced RT-related toxicity at any time. Among them, 83% had G3-4 acute side-effects during RT, mainly dysphagia, mucositis, epithelitis and/or xerostomia (DMEX). 28/105 patients (27%) had early G3-4 toxicity up to 3months after the end of RT. 29/96 patients (30%) had G3-4 late toxicity thereafter. The presence of G allele of MDM2 or Thr allele of ERCC1 was associated with a significantly higher risk of acute and/or early DMEX toxicity. The MDM2 309GG genotype was linked to a higher risk of acute G3-4 dermatitis. The ERCC5 TT genotype was associated with more frequent G3-4 late cervical skin fibrosis or xerostomia. Pro allele of TP53 72 was associated with a higher risk of G3-4 osteoradionecrosis.Conclusion: Relevant SNPs in DNA repair (ERCC1 and ERCC5) and apoptosis (MDM2 and TP53) genes might influence the severity of radiation-related side-effects in HNSCC patients. Prospective clinical SNP-based validation studies are needed on these bases. (C) 2017 Elsevier Ltd. All rights reserved.