PDF(Pubmed)
Abstract：
The response to radiation therapy (RT) is closely associated with DNA damage repair. X-ray repair cross-complementing group-1 (XRCC1) is a key gene in the DNA damage repair pathway, and SNPs in this gene alter the expression and activity of its effector protein, which may in turn affect sensitivity to RT. Therefore, the course of tumor treatment and local control rate can be influenced. In the present study, a group of 158 patients with nasopharyngeal carcinoma (NPC) who received intensity-modulated RT at Fujian Cancer Hospital (Fuzhou, China) between July 2012 and October 2013 were included in retrospective chart review and followed up. Plasma was collected before treatment for genotype analysis of the three SNPs of XRCC1, namely Arg194Trp, Arg280His and Arg399Gln. Acute radiation-induced injuries sustained during treatment was graded according to the Radiation Therapy Oncology Group scoring criteria. Post-treatment follow-up was performed until August 2020. In the 158 cases of NPC, no statistically significant association was observed between the three SNPs of the XRCC1 gene and the severity of acute radiation-induced injury or prognosis. However, the AA genotype of XRCC1-Arg399Gln tended to be associated with worse progression-free survival (PFS) compared with the GA + GG genotype, although this was not significant (P=0.069). In addition, multivariate logistic analysis showed that nodal stage was significantly associated with the occurrence of acute severe radiation-induced oral mucositis (P=0.018), and there was also a trend towards an association between nodal stage and the incidence of acute severe radiation-induced pharyngitis; however, this was not statistically significant (P=0.061). Furthermore, multivariate Cox regression analysis showed that older age, distant metastasis and higher clinical stage were independent risk factors for PFS in patients with NPC. In conclusion, relying solely on the aforementioned SNPs of the XRCC1 gene may not provide a robust enough basis to predict the response to RT or prognosis in patients with NPC.
摘要：
放射治疗（RT）的反应与DNA损伤修复密切相关。X线修复交叉互补组1(XRCC1)是DNA损伤修复途径中的关键基因,并且该基因中的SNP改变了其效应蛋白的表达和活性，这反过来可能会影响对RT的敏感性。因此,可影响肿瘤的治疗过程和局部控制率。在本研究中,一组158例鼻咽癌（NPC）患者在福建省肿瘤医院接受了调强放疗（福州，中国）在2012年7月至2013年10月期间被纳入回顾性图表审查和随访。在治疗前收集血浆，用于XRCC1的三个SNP的基因型分析，即Arg194Trp，Arg280His和Arg399Gln.根据放射治疗肿瘤学组评分标准对治疗期间持续的急性放射性损伤进行分级。治疗后随访至2020年8月。在158例NPC中，在XRCC1基因的3个SNP与急性放射损伤的严重程度或预后之间未观察到统计学显著关联.然而,与GA+GG基因型相比，XRCC1-Arg399Gln的AA基因型倾向于与更差的无进展生存期(PFS)相关，尽管这并不显著(P=0.069)。此外,多因素logistic分析显示淋巴结分期与急性重度放射性口腔黏膜炎的发生显著相关(P=0.018)。淋巴结分期与急性严重放射性咽炎的发病率之间也有关联的趋势；然而，这没有统计学意义(P=0.061).此外，多因素Cox回归分析显示,年龄较大,远处转移和较高的临床分期是鼻咽癌患者PFS的独立危险因素。总之,仅依靠上述XRCC1基因的SNP可能无法提供足够可靠的基础来预测NPC患者对RT的应答或预后.
