title: Genetic polymorphisms of Wnt/β-catenin pathway genes are associated with the efficacy and toxicities of radiotherapy in patients with nasopharyngeal carcinoma.
abstract: 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.
authors: Center of Clinical Pharmacology, The Third Xiangya Hospital, Central South University, Changsha, Hunan 410013, China.
authors: Jingjing
authors: J
authors: Yu
authors: Department of Radiation Oncology, Jiangxi Province Tumor Hospital, Nanchang, Jiangxi 330029, China.
authors: Yuling
authors: Y
authors: Huang
authors: Department of Pharmacy, Jiangxi Cancer Hospital, Nanchang 330029, China.
authors: Lijuan
authors: L
authors: Liu
authors: Department of Radiation Oncology, Jiangxi Province Tumor Hospital, Nanchang, Jiangxi 330029, China.
authors: Jing
authors: J
authors: Wang
authors: Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China.
authors: Jiye
authors: J
authors: Yin
authors: Center for Medical Experiments, The Third Xiangya Hospital, Central South University, Changsha, Hunan 410013, China.
authors: Lihua
authors: L
authors: Huang
authors: Department of Oncology, Fourth Affiliated Hospital, Guangxi Medical University, Liuzhou, Guangxi 545005, China.
authors: Shaojun
authors: S
authors: Chen
authors: Department of Radiation Oncology, Jiangxi Province Tumor Hospital, Nanchang, Jiangxi 330029, China.
authors: Jingao
authors: J
authors: Li
authors: Center of Clinical Pharmacology, The Third Xiangya Hospital, Central South University, Changsha, Hunan 410013, China.
authors: Hong
authors: H
authors: Yuan
authors: Center of Clinical Pharmacology, The Third Xiangya Hospital, Central South University, Changsha, Hunan 410013, China.
authors: Guoping
authors: G
authors: Yang
authors: College of Pharmacy, Central South University, Changsha, Hunan 410008, China.
authors: Wenyu
authors: W
authors: Liu
authors: Xiangya Medical College, Central South University, Changsha, Hunan 410008, China.
authors: Hai
authors: H
authors: Wang
authors: Center of Clinical Pharmacology, The Third Xiangya Hospital, Central South University, Changsha, Hunan 410013, China.
authors: Qi
authors: Q
authors: Pei
authors: Center of Clinical Pharmacology, The Third Xiangya Hospital, Central South University, Changsha, Hunan 410013, China.
authors: Chengxian
authors: C
authors: Guo
mesh_terms: D025601:Adenomatous Polyposis Coli Protein / Q000235:genetics; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics*; D002277:Carcinoma / Q000235:genetics* / Q000473:pathology / Q000532:radiotherapy*; D005260:Female; D020022:Genetic Predisposition to Disease; D000071679:Glycogen Synthase Kinase 3 beta / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D000077274:Nasopharyngeal Carcinoma; D009303:Nasopharyngeal Neoplasms / Q000235:genetics* / Q000473:pathology / Q000532:radiotherapy*; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D011855:Radiodermatitis / Q000235:genetics; D011878:Radiotherapy / Q000009:adverse effects; D012307:Risk Factors; D013280:Stomatitis / Q000235:genetics; D016896:Treatment Outcome; D060449:Wnt Signaling Pathway / Q000235:genetics*; D051154:Wnt2 Protein / Q000235:genetics; D055815:Young Adult; D051176:beta Catenin / Q000235:genetics
chemical_list: C555337:APC protein, human; D025601:Adenomatous Polyposis Coli Protein; D014408:Biomarkers, Tumor; C495270:CTNNB1 protein, human; C495244:WNT2 protein, human; D051154:Wnt2 Protein; D051176:beta Catenin; C000605506:GSK3B protein, human; D000071679:Glycogen Synthase Kinase 3 beta
keywords: Wnt/β-catenin pathway; curative efficacy; nasopharyngeal carcinoma (NPC); single nucleotide polymorphism (SNP); toxic reaction