Yu Jingjing, Huang Yuling, Liu Lijuan, Wang Jing, Yin Jiye, Huang Lihua, Chen Shaojun, Li Jingao, Yuan Hong, Yang Guoping, Liu Wenyu, Wang Hai, Pei Qi, Guo Chengxian
Center of Clinical Pharmacology, The Third Xiangya Hospital, Central South University, Changsha, Hunan 410013, China.
Department of Radiation Oncology, Jiangxi Province Tumor Hospital, Nanchang, Jiangxi 330029, China.
Oncotarget. 2016 Dec 13;7(50):82528-82537. doi: 10.18632/oncotarget.12754.
Radiotherapy (RT) is the normative therapeutic treatment for primary nasopharyngeal carcinoma (NPC). Single nucleotide polymorphisms (SNPs) of genes in Wnt/β-catenin pathway are correlated to the development, prognosis, and treatment benefit of various cancers. However, it has not been established whether SNPs of Wnt/β-catenin pathway are associated with nasopharyngeal tumorigenesis and the efficacy of RT in NPC patients. Therefore, in this study, we aimed to investigate the nine potentially functional SNPs of four genes in the Wnt/β-catenin pathway and genotyped these in 188 NPC patients treated with RT. To achieve this goal, associations between these SNPs and the RT's curative efficacy, as well as acute radiation-induced toxic reaction were determined by multifactorial logistic regression. We observed that catenin beta 1 gene (CTNNB1) rs1880481 and rs3864004, and glycogen synthase kinase 3 beta gene (GSK3β) rs3755557 polymorphisms were significantly associated with poorer efficacy of RT in NPC patients. Moreover, GSK3β rs375557 and adenomatous polyposis coli gene (APC) rs454886 polymorphisms were correlated with acute grade 3-4 radiation-induced dermatitis and oral mucositis, respectively. In conclusion, this study suggests that gene polymorphisms of Wnt/β-catenin may be novel prognostic factors for NPC patients treated with RT.
放射治疗(RT)是原发性鼻咽癌(NPC)的标准治疗方法。Wnt/β-连环蛋白通路中基因的单核苷酸多态性(SNP)与多种癌症的发生、预后及治疗获益相关。然而,Wnt/β-连环蛋白通路的SNP是否与鼻咽癌的发生及NPC患者放疗疗效相关尚未明确。因此,在本研究中,我们旨在调查Wnt/β-连环蛋白通路中四个基因的九个潜在功能性SNP,并对188例接受放疗的NPC患者进行基因分型。为实现这一目标,通过多因素逻辑回归确定这些SNP与放疗疗效以及急性放射性毒性反应之间的关联。我们观察到,连环蛋白β1基因(CTNNB1)的rs1880481和rs3864004,以及糖原合酶激酶3β基因(GSK3β)的rs3755557多态性与NPC患者放疗疗效较差显著相关。此外,GSK3β的rs375557和腺瘤性息肉病基因(APC)的rs454886多态性分别与急性3-4级放射性皮炎和口腔黏膜炎相关。总之,本研究表明Wnt/β-连环蛋白的基因多态性可能是接受放疗的NPC患者新的预后因素。