Genetic polymorphisms of Wnt/β-catenin pathway genes are associated with the efficacy and toxicities of radiotherapy in patients with nasopharyngeal carcinoma

• Published in: Oncotarget 2016-12, Vol.7 (50), p.82528-82537
• Main Authors: 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
• Format: Article
• Language: English
• Subjects: Adenomatous Polyposis Coli Protein - genetics; Adolescent; Adult; Aged; Aged, 80 and over; beta Catenin - genetics; Biomarkers, Tumor - genetics; Carcinoma - genetics; Carcinoma - pathology; Carcinoma - radiotherapy; Female; Genetic Predisposition to Disease; Glycogen Synthase Kinase 3 beta - genetics; Humans; Male; Middle Aged; Nasopharyngeal Carcinoma; Nasopharyngeal Neoplasms - genetics; Nasopharyngeal Neoplasms - pathology; Nasopharyngeal Neoplasms - radiotherapy; Phenotype; Polymorphism, Single Nucleotide; Radiodermatitis - genetics; Radiotherapy - adverse effects; Research Paper; Risk Factors; Stomatitis - genetics; Treatment Outcome; Wnt Signaling Pathway - genetics; Wnt2 Protein - genetics; Young Adult
• ISSN: 1949-2553; 1949-2553
• 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.