title: Polymorphisms in the endothelin-1 and endothelin a receptor genes and survival in patients with locoregionally advanced nasopharyngeal carcinoma.
abstract: OBJECTIVE
  We aimed to investigate the prognostic role of endothelin-1 (EDN1) and endothelin A receptor (EDNRA) gene polymorphisms in patients with locoregionally advanced nasopharyngeal carcinoma (NPC).
  
  
  METHODS
  Two hundred three consecutive patients with locoregionally advanced NPC were enrolled. Seven potentially functional polymorphisms in the EDN1 and EDNRA genes were determined by ligase detection reaction-PCR method from prospectively collected blood samples. The influence of the genetic polymorphisms on patient overall survival (OS) was analyzed using Cox proportional hazards model, Kaplan-Meier method, and the log-rank test.
  
  
  RESULTS
  The 5-year OS in patients with EDNRA/H323H TT, TC, and CC genotypes were 81.3%, 62.1%, and 75.0%, respectively (P = 0.004). Patients carrying the heterozygous (TC) or homozygous variant (CC) genotype in EDNRA/H323H were combined for analysis, which revealed that the 5-year OS in patients with TC/CC genotypes was significantly lower than those with the wild-type TT genotype (63.2% vs. 81.3%; P = 0.002). Multivariate analysis showed that EDNRA/H323H polymorphism (HR: 1.95; 95% CI: 1.18-3.23; P = 0.009) and N classification (HR: 1.35; 95% CI: 1.03-1.79; P = 0.03) were independent significant prognostic factors for OS in patients with locoregionally advanced NPC. In contrast, the EDN1 polymorphisms revealed no prognostic value.
  
  
  CONCLUSIONS
  The EDNRA/H323H polymorphism was a novel and independent prognostic marker for patients with locoregionally advanced NPC. The analysis of EDNRA/H323H polymorphism may help identify patient subgroups at high risk for poor disease outcome.
authors.affiliation: State Key Laboratory of Oncology in South China, Department of Nasopharyngeal Carcinoma, Sun Yat-sen University Cancer Center, Guangzhou, PR China.
authors.forename: Yue-Feng
authors.initials: YF
authors.lastname: Wen
authors.forename: Bin
authors.initials: B
authors.lastname: Qi
authors.forename: Huai
authors.initials: H
authors.lastname: Liu
authors.forename: Hao-Yuan
authors.initials: HY
authors.lastname: Mo
authors.forename: Qiu-Yan
authors.initials: QY
authors.lastname: Chen
authors.forename: Juan
authors.initials: J
authors.lastname: Li
authors.forename: Pei-Yu
authors.initials: PY
authors.lastname: Huang
authors.forename: Yan-Fang
authors.initials: YF
authors.lastname: Ye
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhang
authors.forename: Man-Quan
authors.initials: MQ
authors.lastname: Deng
authors.forename: Xiang
authors.initials: X
authors.lastname: Guo
authors.forename: Ming-Huang
authors.initials: MH
authors.lastname: Hong
authors.forename: Ka-Jia
authors.initials: KJ
authors.lastname: Cao
authors.forename: Hai-Qiang
authors.initials: HQ
authors.lastname: Mai
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics; D002277:Carcinoma; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D019332:Endothelin-1 / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D000077274:Nasopharyngeal Carcinoma; D009303:Nasopharyngeal Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D017063:Outcome Assessment, Health Care / Q000706:statistics & numerical data; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D016016:Proportional Hazards Models; D044022:Receptor, Endothelin A / Q000235:genetics*; D012307:Risk Factors; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; D019332:Endothelin-1; D044022:Receptor, Endothelin A