Polymorphisms in the Endothelin-1 and Endothelin A Receptor Genes and Survival in Patients with Locoregionally Advanced Nasopharyngeal Carcinoma

Abstract

Purpose: 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).Experimental Design: 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 ¼ 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 ¼ 0.002). Multivariate analysis showed that EDNRA/H323H polymorphism (HR: 1.95; 95% CI: 1.18-3.23; P ¼ 0.009) and N classification (HR: 1.35; 95% CI: 1.03-1.79; P ¼ 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.

Endothelin‐1 gene polymorphism in sudden sensorineural hearing loss

“…Endothelin‐1 has various biological functions . The endothelin‐1 system is involved in the regulation of apoptosis, in the autocrine actions (such as proinflammatory, vasoconstrictor, and mitogenic actions), and may contribute to tumor growth and modulate tumor‐host interactions …”

“…7 The endothelin-1 system is involved in the regulation of apoptosis, in the autocrine actions (such as proinflammatory, vasoconstrictor, and mitogenic actions), and may contribute to tumor growth and modulate tumor-host interactions. 20,21 The phenotypic functional role of this polymorphism is not straightforward. Rankinen et al observed a significant effect of the interaction between the genotype and cardiorespiratory fitness level on the risk of hypertension.…”

Genetic Variations in Radiation and Chemotherapy Drug Action Pathways and Survival in locoregionally Advanced Nasopharyngeal Carcinoma Treated with Chemoradiotherapy

“…Overall, we selected 18 SNPs from 13 major genes (Table 2). Genotyping of the SNPs was performed by the Shanghai BioWing Applied Biotechnology Company (BioWing, Shanghai, China) using the ligase detection reaction- polymerase chain reaction (LDR-PCR) technique [28,29]. To validate the genotyping results, 10% of the samples were randomly selected for genotyping by a second investigator; the agreement rate was 100%.…”

The endothelin axis in head and neck cancer: a promising therapeutic opportunity?

“…For example, Wen et al. investigated EDN1 and the ET A R gene ( EDNRA) polymorphisms in 203 patients with locoregionally advanced NPC by ligase detection reaction PCR. They found that the presence of the EDNRA /H323H polymorphism significantly and independently lowered 5‐year overall survival of patients compared with wild type, whereas EDN1 polymorphisms had no effect.…”